Gene model for the ortholog of Protein tyrosine phosphatase 61F (Ptp61F) in the May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly (GenBank AccessionGCA_000005115.1) of Drosophila ananassae.
","acknowledgements":"We would like to thank Wilson Leung for developing and maintaining the technological infrastructure that was used to create this gene model and Laura K. Reed for overseeing the project. Thank you to FlyBase for providing the definitive database for Drosophila melanogaster gene models. FlyBase is supported by grants: NHGRI U41HG000739 and U24HG010859, UK Medical Research Council MR/W024233/1, NSF 2035515 and 2039324, BBSRC BB/T014008/1, and Wellcome Trust PLM13398.","authors":[{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","validation","writing_originalDraft","writing_reviewEditing"],"email":"aebacklund@crimson.ua.edu","firstName":"Anne E.","lastName":"Backlund","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0003-2494-2388"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["dataCuration","validation","visualization","writing_reviewEditing"],"email":"lcohen5@worcester.edu","firstName":"Logan","lastName":"Cohen","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-2961-0334"},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"priyav1129@gmail.com","firstName":"Priya","lastName":"Vaid","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0001-8770-9589"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"chloenason@icloud.com","firstName":"Chloe","lastName":"Nason","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"kfkneuper@gmail.com","firstName":"Kara","lastName":"Kneuper","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"ajademiller13@gmail.com","firstName":"Ali Jade","lastName":"Miller","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"chris.ellison@rutgers.edu","firstName":"Christopher E.","lastName":"Ellison","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-0350-0962"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"lindsey.long@oc.edu","firstName":"Lindsey J.","lastName":"Long","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4524-9307"},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"lreed1@ua.edu","firstName":"Laura K.","lastName":"Reed","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4381-494X"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["writing_originalDraft"],"email":"dbarnard@worcester.edu","firstName":"Daron","lastName":"Barnard","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["dataCuration","formalAnalysis","methodology","project","software","supervision","validation","visualization","writing_reviewEditing"],"email":"cprele@ua.edu","firstName":"Chinmay P.","lastName":"Rele","submittingAuthor":true,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":"0000-0002-3473-9319"}],"awards":[],"conflictsOfInterest":null,"dataTable":null,"extendedData":[{"description":"Zip file containing FASTA, PEP, and GFF","doi":null,"resourceType":"Model","name":"DanaCAF1_Ptp62F.zip","url":"https://portal.micropublication.org/uploads/7a855675834516099ae5ba647e373621.zip"}],"funding":"This material is based upon work supported by the National Science Foundation (1915544) and the National Institute of General Medical Sciences of the National Institutes of Health (R25GM130517) to the Genomics Education Partnership (GEP; https://thegep.org/; PI-LKR). Any opinions, findings, and conclusions or recommendations expressed in this material are solely those of the author(s) and do not necessarily reflect the official views of the National Science Foundation nor the National Institutes of Health.","image":{"url":"https://portal.micropublication.org/uploads/5c2c56a29d3f844c92e535f9e35b6955.png"},"imageCaption":"(A) Synteny comparison of the genomic neighborhoods for Ptp61F in Drosophila melanogaster and Drosophila ananassae. Thin underlying arrows indicate the DNA strand within which the target gene–Ptp61F–is located in D. melanogaster (top) and D. ananassae (bottom). The thin arrow pointing to the right indicates that Ptp61F is on the positive (+) strand in Drosophila ananassae, and the thin arrow pointing to the left indicates that Ptp61F is on the negative (-) strand in D. melanogaster. The wide gene arrows pointing in the same direction as Ptp61F are on the same strand relative to the thin underlying arrows, while wide gene arrows pointing in the opposite direction of Ptp61F are on the opposite strand relative to the thin underlying arrows. White gene arrows in Drosophila ananassae indicate orthology to the corresponding gene in D. melanogaster, while black gene arrows indicate non-orthology. Gene symbols given in the Drosophila ananassae gene arrows indicate the orthologous gene in D. melanogaster, while the locus identifiers are specific to Drosophila ananassae. (B) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The coding-regions of Ptp61F in Drosophila ananassae are displayed in the User Supplied Track (black); coding exons are depicted by thick rectangles and introns by thin lines with arrows indicating the direction of transcription. Subsequent evidence tracks include BLAT Alignments of NCBI RefSeq Genes (dark blue, alignment of Ref-Seq genes for Drosophila ananassae), Spaln of D. melanogaster Proteins (purple, alignment of Ref-Seq proteins from D. melanogaster), Transcripts and Coding Regions Predicted by TransDecoder (dark green), RNA-Seq from Adult Females, Adult Males, and Wolbachia-cured Embryos (red, light blue, and pink, respectively; alignment of Illumina RNA-Seq reads from Drosophila ananassae), and Splice Junctions Predicted by regtools using Drosophila ananassae RNA-Seq (SRP006203, SRP007906, PRJNA257286, PRJNA388952). Splice junctions shown have a minimum read-depth of 10 with 50-99, 100-499, 500-999, >1000 supporting reads in green, pink, brown, and red, respectively. (C) Dot Plot of Ptp61F-PA in D. melanogaster(x-axis) vs. the orthologous peptide in Drosophila ananassae (y-axis). Amino acid number is indicated along the left and bottom; coding-exon number is indicated along the top and right, and exons are also highlighted with alternating colors. Line breaks in the dot plot indicate mismatching amino acids at the specified location between species. (D) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The same evidence tracks as Figure 1B are shown in this image. We hypothesize that the isoform Ptp61F-PC does not exist in D. ananassae. In addition, we hypothesize that there is a novel isoform, Ptp61F-PNF.
","imageTitle":"","methods":"The Genomics Education Partnership maintains a mirror of the UCSC Genome Browser v.435 (Kent WJ et al., 2002; Navarro Gonzalez et al., 2021), which is available at https://gander.wustl.edu. Detailed methods including algorithms, database versions, and citations for the complete annotation process can be found in Rele et al. (2023).
","reagents":"","patternDescription":"Introduction
“Computational gene predictions in non-model organisms often can be improved by careful manual annotation and curation, allowing for more accurate analyses of gene and genome evolution (Mudge and Harrow 2016; Tello-Ruiz et al., 2019). The Genomics Education Partnership (thegep.org) uses web-based tools to allow undergraduates to participate in course-based research by generating manual annotations of genes in non-model species (Rele et al., 2023). These models of orthologous genes across species, such as the one presented here, then provide a reliable basis for further evolutionary genomic analyses when made available to the scientific community. The particular gene ortholog described here Protein tyrosine phosphatase 61F (Ptp61F) in D. ananassae was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila.” (Myers et al., 2023) “The IIS pathway is a highly conserved signaling pathway in animals and is central to mediating organismal responses to nutrients (Hietakangas and Cohen 2009; Grewal 2009).” (Myers et al., 2023).
The protein product of Ptp61F (PTP61) negatively regulates the Insulin/TOR pathway by dephosphorylating the insulin receptor (InR) (Wu et al., 2011; Buszard et al., 2013). PTP61Fm-mediated dephosphorylation of InR requires an interaction with the SH2/SH3 adaptor protein Dock (dreadlocks) while PTP61Fn dephosphorylates InR in a Dock-independent manner (Clemens et al., 1996; Buszard et al., 2013; Willoughby et al., 2017). The Ptp61F gene in Drosophila melanogaster was first isolated using rat PTP61F cDNA in a low stringency hybridization screening method (McLaughlin and Dixon 1993). Ptp61F is differentially spliced where the longer isoform (PTP61Fm) is targeted to the ER by the hydrophobic C-terminal domain, and the shorter isoform (PTP61Fn) is targeted to the nucleus by a nuclear localization signal (NLS) (McLaughlin and Dixon 1993). PTP61F plays a role in the regulation of a variety of signaling pathways through negative regulation of tyrosine kinases including Janus kinase/signal transducers and activators of transcription (JAK/STAT), Mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR), and platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) (Baeg et al., 2005; Buszard et al., 2013; Tchankouo-Nguetcheu et al., 2014; Willoughby et al., 2017).
We propose a gene model for the Drosophila ananassae ortholog of the D. melanogaster Protein tyrosine phosphatase 61F (Ptp61F) gene. The genomic region of the ortholog corresponds to the uncharacterized protein XP_014764155.1 (Locus ID LOC6492936) in the May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly of Drosophila ananassae (GCA_000005115.1 - Graveley et al., 2011). This model is based on RNA-Seq data from Drosophila ananassae (SRP006203, SRP007906, PRJNA257286, PRJNA388952) and Ptp61F in D. melanogaster using FlyBase release FB2023_03 (GCA_000001215.4) (Larkin et al., 2021; Gramates et al., 2022).
“D. ananassae is part of the melanogaster species group within the subgenus Sophophora of the genus Drosophila (Sturtevant 1939; Bock and Wheeler 1972). It was first described by Doeschall (1858). D. ananassae is circumtropical (Markow and O’Grady 2006; https://www.taxodros.uzh.ch, accessed 1 Feb 2023), and often associated with human settlement (Singh 2010). It has been extensively studied as a model for its cytogenetic and genetic characteristics, and in experimental evolution (Kikkawa 1938; Singh and Yadav 2015).” (Lawson et al., 2023).
Synteny
The target gene, Ptp61F, occurs on chromosome 3L in D. melanogaster and is flanked upstream by rhomboid (rho) and Stromalin 2 (SA2) and downstream by indra and Hydroxymethylbilane synthase (Hmbs). There are also 6 genes nested within Ptp61F in D. melanogaster: CG9173, FucTD, CG9168, CG32320, ru, and CG9166. The tblastn search of D. melanogaster Ptp61F-PA (query) against the Drosophila ananassae (GenBank Accession: GCA_000005115.1) Genome Assembly (database) placed the putative ortholog of Ptp61F within scaffold_13337 at locus LOC6492936 (XP_014764155.1)— with an E-value of 7e-28 and a percent identity of 84.48%. Furthermore, the putative ortholog is flanked upstream by LOC6492935 (XP_001956685.1) and LOC6507090 (XP_001956686.1), which correspond to Reg2 and CG9166 in D. melanogaster (E-value: 0.0 and 2e-140; identity: 89.62% and 83.55%, respectively, as determined by blastp) (Figure 1A; Altschul et al., 1990). The putative ortholog of Ptp61F is flanked downstream by LOC6492937 (XP_ 001956688.1) and LOC6507089 (XP_ 001956689.1), which correspond to indra and Hmbs in D. melanogaster (E-value: 2e-96 and 0.0; identity: 32.20% and 86.85%, respectively, as determined by blastp). The putative ortholog assignment for Ptp61F in Drosophila ananassae is supported by the following evidence: The blastp and tblastn results support the presence of a Ptp61F ortholog in this location in D. ananassae although synteny is not completely conserved. In D. melanogaster, the Ptp61F-PC isoform has 6 genes nested within it, but this characteristic is not present in D. ananassae, so we hypothesize that the Ptp61F-PC isoform does not exist in this species. CG9166 is present in both genomic neighborhoods, but in slightly different locations (i.e., not nested within Ptp61F), and the first and second downstream genes (indra and Hmbs) are orthologous. Therefore, we conclude that LOC6492936 is the correct ortholog of Ptp61F in D. ananassae (Figure 1A).
Protein Model
Ptp61F in D. melanogaster has five protein-coding isoforms: Ptp61F-PA, Ptp61F-PB, Ptp61F-PC, Ptp61F-PD, and Ptp61F-PE. Ptp61F-PE and Ptp61F-PD have identical coding sequences. mRNA soform Ptp61F-RA contains six protein-coding exons, Ptp61F-RB and Ptp61F-RC have seven protein-coding exons, and Ptp61F-RD and Ptp61F-RE have four protein-coding exons. In D. ananassae, the isoform count is not conserved (see Special characteristics of the protein model), and we predict five total isoforms (Ptp61F-PA, Ptp61F-PB, Ptp61F-PD, Ptp61F-PE,and Ptp61F-PNF). The sequence of Ptp61F-PA in Drosophila ananassae has 76.87% identity (E-value: 0.0) with the protein-coding isoform Ptp61F-PA in D. melanogaster, as determined by blastp (Figure 1C). Coordinates of this curated gene model are stored by NCBI at GenBank/BankIt (accession BKXXXXXX). These data are also archived in the CaltechDATA repository (see “Extended Data” section below).
Special characteristics of the protein model
We hypothesize that the isoform Ptp61F-RC does not exist in D. ananassae. In addition, we hypothesize that there is a new isoform, Ptp61F-RNF, due to alternative splicing. Ptp61F-RC in D. melanogaster has a long first intron that has six genes nested within it, but this does not appear in D. ananassae (Figure 1A). A tblastn search of the amino acid sequence of the first exon in Ptp61F-RC in D. melanogaster against the D. ananassae genome did not return any results, and there are no predicted splice junctions consistent with a long first intron for Ptp61F-RC in this species. This leads us to conclude that the Ptp61F-RC isoform is not present in D. ananassae. Finally, we determined that XM_032453921 (LOC6492936) is a novel isoform, as there is not an orthologous isoform in D. melanogaster that has the same gene structure. It has seven protein-coding exons, and its sixth exon is longer than the corresponding exon in isoform Ptp61F-RB (Figure 1D).The seventh exon of the proposed novel isoform is only eight base pairs long (including the stop codon), as compared to 37 base pairs long for the seventh exon of isoform Ptp61F-RB. The sixth and seventh exons of this novel isoform are supported by a splice junction with a score of 457 (Figure 1D, shown in pink). These features of XM_032453921 (LOC6492936) lead us to believe that alternative splicing has occurred, resulting in a novel isoform. We propose that this isoform be named Ptp61F-RNF.
","references":[{"reference":"Altschul, S F, Gish, W, Miller, W, Myers, E W, Lipman, D J 1990. Basic local alignment search tool. J Mol Biol. 215: 403-410.","pubmedId":"2231712","doi":"10.1016/S0022-2836(05)80360-2"},{"reference":"Baeg, Gyeong-Hun, Zhou, Rui, Perrimon, Norbert 2005. Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila. Genes Dev. 19: 1861-1870.","pubmedId":"16055650","doi":"10.1101/gad.1320705"},{"reference":"BOCK I. R. 1972. The Drosophila melanogaster species-group. The University of Texas Publication. 7213: 1-102. FBrf0024428..","pubmedId":"","doi":""},{"reference":"Buszard, Bree J, Johnson, Travis K, Meng, Tzu-Ching, Burke, Richard, Warr, Coral G, Tiganis, Tony 2013. The nucleus- and endoplasmic reticulum-targeted forms of protein tyrosine. Mol Cell Biol. 33: 1345-1356.","pubmedId":"23339871","doi":"10.1128/MCB.01411-12"},{"reference":"Clemens, J C, Ursuliak, Z, Clemens, K K, Price, J V, Dixon, J E 1996. 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Biochem J. 439: 151-159.","pubmedId":"","doi":"10.1042/BJ20110799"}],"title":"Gene model for the ortholog of Ptp61F in Drosophila ananassae
","reviews":[],"curatorReviews":[{"curator":{"displayName":"FlyBase Curators"},"openAcknowledgement":false,"submitted":null}]},{"id":"fb27507d-d348-4015-9335-97eaad3b6ac7","decision":"edit","abstract":"Gene model for the ortholog of Protein tyrosine phosphatase 61F (Ptp61F) in the D. ananassae May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly (GenBank Accession: GCA_000005115.1 ) of Drosophila ananassae. This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.
","acknowledgements":"We would like to thank Wilson Leung for developing and maintaining the technological infrastructure that was used to create this gene model and Laura K. Reed for overseeing the project. Thank you to FlyBase for providing the definitive database for Drosophila melanogaster gene models. FlyBase is supported by grants: NHGRI U41HG000739 and U24HG010859, UK Medical Research Council MR/W024233/1, NSF 2035515 and 2039324, BBSRC BB/T014008/1, and Wellcome Trust PLM13398.
","authors":[{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","validation","writing_originalDraft","writing_reviewEditing"],"email":"aebacklund@crimson.ua.edu","firstName":"Anne E.","lastName":"Backlund","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0003-2494-2388"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["dataCuration","validation","visualization","writing_reviewEditing"],"email":"lcohen5@worcester.edu","firstName":"Logan","lastName":"Cohen","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-2961-0334"},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"priyav1129@gmail.com","firstName":"Priya","lastName":"Vaid","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0001-8770-9589"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"chloenason@icloud.com","firstName":"Chloe","lastName":"Nason","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"kfkneuper@gmail.com","firstName":"Kara","lastName":"Kneuper","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"ajademiller13@gmail.com","firstName":"Ali Jade","lastName":"Miller","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"chris.ellison@rutgers.edu","firstName":"Christopher E.","lastName":"Ellison","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-0350-0962"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"lindsey.long@oc.edu","firstName":"Lindsey J.","lastName":"Long","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4524-9307"},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"lreed1@ua.edu","firstName":"Laura K.","lastName":"Reed","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4381-494X"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["writing_originalDraft"],"email":"dbarnard@worcester.edu","firstName":"Daron","lastName":"Barnard","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["dataCuration","formalAnalysis","methodology","project","software","supervision","validation","visualization","writing_reviewEditing"],"email":"cprele@ua.edu","firstName":"Chinmay P.","lastName":"Rele","submittingAuthor":true,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":"0000-0002-3473-9319"}],"awards":[],"conflictsOfInterest":null,"dataTable":null,"extendedData":[{"description":"Zip file containing FASTA, PEP, and GFF","doi":null,"resourceType":"Model","name":"DanaCAF1_Ptp62F.zip","url":"https://portal.micropublication.org/uploads/7a855675834516099ae5ba647e373621.zip"}],"funding":"This material is based upon work supported by the National Science Foundation under Grant No. IUSE-1915544 to LKR and the National Institute of General Medical Sciences of the National Institutes of Health Award R25GM130517 to LKR. The Genomics Education Partnership is fully financed by Federal moneys. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
","image":{"url":"https://portal.micropublication.org/uploads/5c2c56a29d3f844c92e535f9e35b6955.png"},"imageCaption":"(A) Synteny comparison of the genomic neighborhoods for Ptp61F in Drosophila melanogaster and Drosophila ananassae. Thin underlying arrows indicate the DNA strand within which the target gene–Ptp61F–is located in D. melanogaster (top) and D. ananassae (bottom). The thin arrow pointing to the right indicates that Ptp61F is on the positive (+) strand in Drosophila ananassae, and the thin arrow pointing to the left indicates that Ptp61F is on the negative (-) strand in D. melanogaster. The wide gene arrows pointing in the same direction as Ptp61F are on the same strand relative to the thin underlying arrows, while wide gene arrows pointing in the opposite direction of Ptp61F are on the opposite strand relative to the thin underlying arrows. White gene arrows in Drosophila ananassae indicate orthology to the corresponding gene in D. melanogaster, while black gene arrows indicate non-orthology. Gene symbols given in the Drosophila ananassae gene arrows indicate the orthologous gene in D. melanogaster, while the locus identifiers are specific to Drosophila ananassae. (B) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The coding-regions of Ptp61F in Drosophila ananassae are displayed in the User Supplied Track (black); coding CDSs are depicted by thick rectangles and introns by thin lines with arrows indicating the direction of transcription. Subsequent evidence tracks include BLAT Alignments of NCBI RefSeq Genes (dark blue, alignment of Ref-Seq genes for Drosophila ananassae), Spaln of D. melanogaster Proteins (purple, alignment of Ref-Seq proteins from D. melanogaster), Transcripts and Coding Regions Predicted by TransDecoder (dark green), RNA-Seq from Adult Females, Adult Males, and Wolbachia-cured Embryos (red, light blue, and pink, respectively; alignment of Illumina RNA-Seq reads from Drosophila ananassae), and Splice Junctions Predicted by regtools using Drosophila ananassae RNA-Seq (SRP006203, SRP007906, PRJNA257286, PRJNA388952). Splice junctions shown have a minimum read-depth of 10 with 50-99, 100-499, 500-999, >1000 supporting reads in green, pink, brown, and red, respectively. (C) Dot Plot of Ptp61F-PA in D. melanogaster(x-axis) vs. the orthologous peptide in Drosophila ananassae (y-axis). Amino acid number is indicated along the left and bottom; coding-CDS number is indicated along the top and right, and CDSs are also highlighted with alternating colors. Line breaks in the dot plot indicate mismatching amino acids at the specified location between species. (D) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The same evidence tracks as Figure 1B are shown in this image. We hypothesize that the isoform Ptp61F-PC does not exist in D. ananassae. In addition, we hypothesize that there is a novel isoform, Ptp61F-PNF.
","imageTitle":"","methods":"Detailed methods including algorithms, database versions, and citations for the complete annotation process can be found in Rele et al. (2023). Briefly, students use the GEP instance of the UCSC Genome Browser v.435 (https://gander.wustl.edu; Kent WJ et al., 2002; Navarro Gonzalez et al., 2021) to examine the genomic neighborhood of their reference IIS gene in the D. melanogaster genome assembly (Aug. 2014; BDGP Release 6 + ISO1 MT/dm6). Students then retrieve the protein sequence for the D. melanogaster target gene for a given isoform and run it using tblastn against their target Drosophila species genome assembly (Drosophila ananassae (GCA_000005115.1 - Graveley et al., 2011)) on the NCBI BLAST server (https://blast.ncbi.nlm.nih.gov/Blast.cgi, Altschul et al., 1990) to identify potential orthologs. To validate the potential ortholog, students compare the local genomic neighborhood of their potential ortholog with the genomic neighborhood of their reference gene in D. melanogaster. This local synteny analysis includes at minimum the two upstream and downstream genes relative to their putative ortholog. They also explore other sets of genomic evidence using multiple alignment tracks in the Genome Browser, including BLAT alignments of RefSeq Genes, Spaln alignment of D. melanogaster proteins, multiple gene prediction tracks (e.g., GeMoMa, Geneid, Augustus), and modENCODE RNA-Seq from the target species. Genomic structure information (e.g., CDSs, CDS number and boundaries, number of isoforms) for the D. melanogaster reference gene is retrieved through the Gene Record Finder (https://gander.wustl.edu/~wilson/dmelgenerecord/index.html; Rele et al., 2023). Approximate splice sites within the target gene are determined using tblastn using the CDSs from the D. melanogaster reference gene. Coordinates of CDSs are then refined by examining aligned modENCODE RNA-Seq data, and by applying paradigms of molecular biology such as identifying canonical splice site sequences and ensuring the maintenance of an open reading frame across hypothesized splice sites. Students then confirm the biological validity of their target gene model using the Gene Model Checker (https://gander.wustl.edu/~wilson/dmelgenerecord/index.html; Rele et al., 2023), which compares the structure and translated sequence from their hypothesized target gene model against the D. melanogaster reference gene model. At least two independent models for this gene were generated by students under mentorship of their faculty course instructors. These models were then reconciled by a third independent researcher mentored by the project leaders to produce the final model presented here. Note: comparison of 5' and 3' UTR sequence information is not included in this GEP CURE protocol.
","reagents":"","patternDescription":"This article reports a predicted gene model generated by undergraduate work using a structured gene model annotation protocol defined by the Genomics Education Partnership (GEP; thegep.org) for Course-based Undergraduate Research Experience (CURE). The following information may be repeated in other articles submitted by participants using the same GEP CURE protocol for annotating Drosophila species orthologs of Drosophila melanogaster genes in the insulin signaling pathway. \"In this GEP CURE protocol students use web-based tools to manually annotate genes in non-model Drosophila species based on orthology to genes in the well-annotated model organism fruitfly Drosophila melanogaster. The GEP uses web-based tools to allow undergraduates to participate in course-based research by generating manual annotations of genes in non-model species (Rele et al., 2023). Computational-based gene predictions in any organism are often improved by careful manual annotation and curation, allowing for more accurate analyses of gene and genome evolution (Mudge and Harrow 2016; Tello-Ruiz et al., 2019). These models of orthologous genes across species, such as the one presented here, then provide a reliable basis for further evolutionary genomic analyses when made available to the scientific community.” (Myers et al., 2024). “The particular gene ortholog described here was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila. The Insulin/insulin-like growth factor signaling pathway (IIS) is a highly conserved signaling pathway in animals and is central to mediating organismal responses to nutrients (Hietakangas and Cohen 2009; Grewal 2009).” (Myers et al., 2024). “D. ananassae (NCBI:txid7217) is part of the melanogaster species group within the subgenus Sophophora of the genus Drosophila (Sturtevant 1939; Bock and Wheeler 1972). It was first described by Doleschall (1858). D. ananassae is circumtropical (Markow and O'Grady 2005; https://www.taxodros.uzh.ch, accessed 1 Feb 2023), and often associated with human settlement (Singh 2010). It has been extensively studied as a model for its cytogenetic and genetic characteristics, and in experimental evolution (Kikkawa 1938; Singh and Yadav 2015).” (Lawson et al., submitted). |
We propose a gene model for the Drosophila ananassae ortholog of the D. melanogaster Protein tyrosine phosphatase 61F (Ptp61F) gene. The genomic region of the ortholog corresponds to the uncharacterized protein XP_014764155.1 (Locus ID LOC6492936) in the May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly of Drosophila ananassae (GCA_000005115.1 - Graveley et al., 2011). This model is based on RNA-Seq data from Drosophila ananassae (SRP006203, SRP007906, PRJNA257286, PRJNA388952) and Ptp61F in D. melanogaster using FlyBase release FB2023_03 (GCA_000001215.4) (Larkin et al., 2021; Gramates et al., 2022).
The protein product of Ptp61F (PTP61) negatively regulates the Insulin/TOR pathway by dephosphorylating the insulin receptor (InR) (Wu et al., 2011; Buszard et al., 2013). PTP61Fm-mediated dephosphorylation of InR requires an interaction with the SH2/SH3 adaptor protein Dock (dreadlocks) while PTP61Fn dephosphorylates InR in a Dock-independent manner (Clemens et al., 1996; Buszard et al., 2013; Willoughby et al., 2017). The Ptp61F gene in Drosophila melanogaster was first isolated using rat PTP61F cDNA in a low stringency hybridization screening method (McLaughlin and Dixon 1993). Ptp61F is differentially spliced where the longer isoform (PTP61Fm) is targeted to the ER by the hydrophobic C-terminal domain, and the shorter isoform (PTP61Fn) is targeted to the nucleus by a nuclear localization signal (NLS) (McLaughlin and Dixon 1993). PTP61F plays a role in the regulation of a variety of signaling pathways through negative regulation of tyrosine kinases including Janus kinase/signal transducers and activators of transcription (JAK/STAT), Mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR), and platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) (Baeg et al., 2005; Buszard et al., 2013; Tchankouo-Nguetcheu et al., 2014; Willoughby et al., 2017).
Species details can be found in the description above.
Synteny
The target gene, Ptp61F, occurs on chromosome 3L in D. melanogaster and is flanked upstream by rhomboid (rho) and Stromalin 2 (SA2) and downstream by indra and Hydroxymethylbilane synthase (Hmbs). There are also 6 genes nested within Ptp61F in D. melanogaster: CG9173, FucTD, CG9168, CG32320, ru, and CG9166. The tblastn search of D. melanogaster Ptp61F-PA (query) against the Drosophila ananassae (GenBank Accession: GCA_000005115.1) Genome Assembly (database) placed the putative ortholog of Ptp61F within scaffold_13337 at locus LOC6492936 (XP_014764155.1)— with an E-value of 7e-28 and a percent identity of 84.48%. Furthermore, the putative ortholog is flanked upstream by LOC6492935 (XP_001956685.1) and LOC6507090 (XP_001956686.1), which correspond to Reg2 and CG9166 in D. melanogaster (E-value: 0.0 and 2e-140; identity: 89.62% and 83.55%, respectively, as determined by blastp) (Figure 1A; Altschul et al., 1990). The putative ortholog of Ptp61F is flanked downstream by LOC6492937 (XP_ 001956688.1) and LOC6507089 (XP_ 001956689.1), which correspond to indra and Hmbs in D. melanogaster (E-value: 2e-96 and 0.0; identity: 32.20% and 86.85%, respectively, as determined by blastp). The putative ortholog assignment for Ptp61F in Drosophila ananassae is supported by the following evidence: The blastpand tblastn results support the presence of a Ptp61F ortholog in this location in D. ananassae although synteny is not completely conserved. In D. melanogaster, the Ptp61F-PC isoform has 6 genes nested within it, but this characteristic is not present in D. ananassae, so we hypothesize that the Ptp61F-PC isoform does not exist in this species. CG9166 is present in both genomic neighborhoods, but in slightly different locations (i.e., not nested within Ptp61F), and the first and second downstream genes (indra and Hmbs) are orthologous. Therefore, we conclude that LOC6492936 is the correct ortholog of Ptp61F in D. ananassae (Figure 1A).
Protein Model
Ptp61F in D. melanogaster has five protein-coding isoforms: Ptp61F-PA, Ptp61F-PB, Ptp61F-PC, Ptp61F-PD, and Ptp61F-PE. Ptp61F-PE and Ptp61F-PD have identical coding sequences. mRNA soform Ptp61F-RA contains six protein-coding CDSs, Ptp61F-RB and Ptp61F-RC have seven protein-coding CDSs, and Ptp61F-RD and Ptp61F-RE have four protein-coding CDSs. In D. ananassae, the isoform count is not conserved (see Special characteristics of the protein model), and we predict five total isoforms (Ptp61F-PA, Ptp61F-PB, Ptp61F-PD, Ptp61F-PE,and Ptp61F-PNF). The sequence of Ptp61F-PA in Drosophila ananassae has 76.87% identity (E-value: 0.0) with the protein-coding isoform Ptp61F-PA in D. melanogaster, as determined by blastp (Figure 1C). Coordinates of this curated gene model are stored by NCBI at GenBank/BankIt (accessions BK064622, BK064623, BK064624, BK064625, and BK064626). These data are also archived in the CaltechDATA repository (see “Extended Data” section below).
Special characteristics of the protein model
We hypothesize that the isoform Ptp61F-RC does not exist in D. ananassae. In addition, we hypothesize that there is a new isoform, Ptp61F-RNF, due to alternative splicing. Ptp61F-RC in D. melanogaster has a long first intron that has six genes nested within it, but this does not appear in D. ananassae (Figure 1A). A tblastn search of the amino acid sequence of the first CDS in Ptp61F-RC in D. melanogaster against the D. ananassae genome did not return any results, and there are no predicted splice junctions consistent with a long first intron for Ptp61F-RC in this species. This leads us to conclude that the Ptp61F-RC isoform is not present in D. ananassae. Finally, we determined that XM_032453921 (LOC6492936) is a novel isoform, as there is not an orthologous isoform in D. melanogaster that has the same gene structure. It has seven protein-coding CDSs, and its sixth CDS is longer than the corresponding CDS in isoform Ptp61F-RB (Figure 1D).The seventh CDS of the proposed novel isoform is only eight base pairs long (including the stop codon), as compared to 37 base pairs long for the seventh CDS of isoform Ptp61F-RB. The sixth and seventh CDSs of this novel isoform are supported by a splice junction with a score of 457 (Figure 1D, shown in pink). These features of XM_032453921 (LOC6492936) lead us to believe that alternative splicing has occurred, resulting in a novel isoform. We propose that this isoform be named Ptp61F-RNF.
","references":[{"reference":"Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. J Mol Biol 215(3): 403-10.
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","pubmedId":"21707536","doi":""}],"title":"Gene model for the ortholog of Ptp61F in Drosophila ananassae
","reviews":[],"curatorReviews":[{"curator":{"displayName":"FlyBase Curators"},"openAcknowledgement":false,"submitted":null}]},{"id":"75b08e37-863e-44b6-b305-a9146fe650a5","decision":"revise","abstract":"Gene model for the ortholog of Protein tyrosine phosphatase 61F (Ptp61F) in the D. ananassae May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly (GenBank Accession: GCA_000005115.1 ) of Drosophila ananassae. This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.
","acknowledgements":"We would like to thank Wilson Leung for developing and maintaining the technological infrastructure that was used to create this gene model and Laura K. Reed for overseeing the project. Thank you to FlyBase for providing the definitive database for Drosophila melanogaster gene models.
","authors":[{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","validation","writing_originalDraft","writing_reviewEditing"],"email":"aebacklund@crimson.ua.edu","firstName":"Anne E.","lastName":"Backlund","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0003-2494-2388"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["dataCuration","validation","visualization","writing_reviewEditing"],"email":"lcohen5@worcester.edu","firstName":"Logan","lastName":"Cohen","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-2961-0334"},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"priyav1129@gmail.com","firstName":"Priya","lastName":"Vaid","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0001-8770-9589"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"chloenason@icloud.com","firstName":"Chloe","lastName":"Nason","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"kfkneuper@gmail.com","firstName":"Kara","lastName":"Kneuper","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"ajademiller13@gmail.com","firstName":"Ali Jade","lastName":"Miller","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"chris.ellison@rutgers.edu","firstName":"Christopher E.","lastName":"Ellison","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-0350-0962"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"lindsey.long@oc.edu","firstName":"Lindsey J.","lastName":"Long","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4524-9307"},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"lreed1@ua.edu","firstName":"Laura K.","lastName":"Reed","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4381-494X"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["writing_originalDraft"],"email":"dbarnard@worcester.edu","firstName":"Daron","lastName":"Barnard","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["dataCuration","formalAnalysis","methodology","project","software","supervision","validation","visualization","writing_reviewEditing"],"email":"gep@ua.edu","firstName":"Chinmay P.","lastName":"Rele","submittingAuthor":true,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":"0000-0002-3473-9319"}],"awards":[],"conflictsOfInterest":null,"dataTable":null,"extendedData":[{"description":"Zip file containing FASTA, PEP, and GFF","doi":null,"resourceType":"Model","name":"DanaCAF1_Ptp62F.zip","url":"https://portal.micropublication.org/uploads/7a855675834516099ae5ba647e373621.zip"}],"funding":"This material is based upon work supported by the National Science Foundation under Grant No. IUSE-1915544 to LKR and the National Institute of General Medical Sciences of the National Institutes of Health Award R25GM130517 to LKR. The Genomics Education Partnership is fully financed by Federal moneys. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
","image":{"url":"https://portal.micropublication.org/uploads/5c2c56a29d3f844c92e535f9e35b6955.png"},"imageCaption":"(A) Synteny comparison of the genomic neighborhoods for Ptp61F in Drosophila melanogaster and Drosophila ananassae. Thin underlying arrows indicate the DNA strand within which the target gene–Ptp61F–is located in D. melanogaster (top) and D. ananassae (bottom). The thin arrow pointing to the right indicates that Ptp61F is on the positive (+) strand in Drosophila ananassae, and the thin arrow pointing to the left indicates that Ptp61F is on the negative (-) strand in D. melanogaster. The wide gene arrows pointing in the same direction as Ptp61F are on the same strand relative to the thin underlying arrows, while wide gene arrows pointing in the opposite direction of Ptp61F are on the opposite strand relative to the thin underlying arrows. White gene arrows in Drosophila ananassae indicate orthology to the corresponding gene in D. melanogaster, while black gene arrows indicate non-orthology. Gene symbols given in the Drosophila ananassae gene arrows indicate the orthologous gene in D. melanogaster, while the locus identifiers are specific to Drosophila ananassae. (B) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The coding-regions of Ptp61F in Drosophila ananassae are displayed in the User Supplied Track (black); coding CDSs are depicted by thick rectangles and introns by thin lines with arrows indicating the direction of transcription. Subsequent evidence tracks include BLAT Alignments of NCBI RefSeq Genes (dark blue, alignment of Ref-Seq genes for Drosophila ananassae), Spaln of D. melanogaster Proteins (purple, alignment of Ref-Seq proteins from D. melanogaster), Transcripts and Coding Regions Predicted by TransDecoder (dark green), RNA-Seq from Adult Females, Adult Males, and Wolbachia-cured Embryos (red, light blue, and pink, respectively; alignment of Illumina RNA-Seq reads from Drosophila ananassae), and Splice Junctions Predicted by regtools using Drosophila ananassae RNA-Seq (SRP006203, SRP007906, PRJNA257286, PRJNA388952). Splice junctions shown have a minimum read-depth of 10 with 50-99, 100-499, 500-999, >1000 supporting reads in green, pink, brown, and red, respectively. (C) Dot Plot of Ptp61F-PA in D. melanogaster(x-axis) vs. the orthologous peptide in Drosophila ananassae (y-axis). Amino acid number is indicated along the left and bottom; coding-CDS number is indicated along the top and right, and CDSs are also highlighted with alternating colors. Line breaks in the dot plot indicate mismatching amino acids at the specified location between species. (D) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The same evidence tracks as Figure 1B are shown in this image. We hypothesize that the isoform Ptp61F-PC does not exist in D. ananassae. In addition, we hypothesize that there is a novel isoform, Ptp61F-PNF.
","imageTitle":"Genomic neighborhoods for Ptp61F in Drosophila melanogaster and Drosophila ananassae
","methods":"Detailed methods including algorithms, database versions, and citations for the complete annotation process can be found in Rele et al. (2023). Briefly, students use the GEP instance of the UCSC Genome Browser v.435 (https://gander.wustl.edu; Kent WJ et al., 2002; Navarro Gonzalez et al., 2021) to examine the genomic neighborhood of their reference IIS gene in the D. melanogaster genome assembly (Aug. 2014; BDGP Release 6 + ISO1 MT/dm6). Students then retrieve the protein sequence for the D. melanogaster target gene for a given isoform and run it using tblastn against their target Drosophila species genome assembly (Drosophila ananassae (GCA_000005115.1 - Graveley et al., 2011)) on the NCBI BLAST server (https://blast.ncbi.nlm.nih.gov/Blast.cgi, Altschul et al., 1990) to identify potential orthologs. To validate the potential ortholog, students compare the local genomic neighborhood of their potential ortholog with the genomic neighborhood of their reference gene in D. melanogaster. This local synteny analysis includes at minimum the two upstream and downstream genes relative to their putative ortholog. They also explore other sets of genomic evidence using multiple alignment tracks in the Genome Browser, including BLAT alignments of RefSeq Genes, Spaln alignment of D. melanogaster proteins, multiple gene prediction tracks (e.g., GeMoMa, Geneid, Augustus), and modENCODE RNA-Seq from the target species. Genomic structure information (e.g., CDSs, CDS number and boundaries, number of isoforms) for the D. melanogaster reference gene is retrieved through the Gene Record Finder (https://gander.wustl.edu/~wilson/dmelgenerecord/index.html; Rele et al., 2023). Approximate splice sites within the target gene are determined using tblastn using the CDSs from the D. melanogaster reference gene. Coordinates of CDSs are then refined by examining aligned modENCODE RNA-Seq data, and by applying paradigms of molecular biology such as identifying canonical splice site sequences and ensuring the maintenance of an open reading frame across hypothesized splice sites. Students then confirm the biological validity of their target gene model using the Gene Model Checker (https://gander.wustl.edu/~wilson/dmelgenerecord/index.html; Rele et al., 2023), which compares the structure and translated sequence from their hypothesized target gene model against the D. melanogaster reference gene model. At least two independent models for this gene were generated by students under mentorship of their faculty course instructors. These models were then reconciled by a third independent researcher mentored by the project leaders to produce the final model presented here. Note: comparison of 5' and 3' UTR sequence information is not included in this GEP CURE protocol.
","reagents":"","patternDescription":"This article reports a predicted gene model generated by undergraduate work using a structured gene model annotation protocol defined by the Genomics Education Partnership (GEP; thegep.org) for Course-based Undergraduate Research Experience (CURE). The following information may be repeated in other articles submitted by participants using the same GEP CURE protocol for annotating Drosophila species orthologs of Drosophila melanogaster genes in the insulin signaling pathway. \"In this GEP CURE protocol students use web-based tools to manually annotate genes in non-model Drosophila species based on orthology to genes in the well-annotated model organism fruitfly Drosophila melanogaster. The GEP uses web-based tools to allow undergraduates to participate in course-based research by generating manual annotations of genes in non-model species (Rele et al., 2023). Computational-based gene predictions in any organism are often improved by careful manual annotation and curation, allowing for more accurate analyses of gene and genome evolution (Mudge and Harrow 2016; Tello-Ruiz et al., 2019). These models of orthologous genes across species, such as the one presented here, then provide a reliable basis for further evolutionary genomic analyses when made available to the scientific community.” (Myers et al., 2024). “The particular gene ortholog described here was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila. The Insulin/insulin-like growth factor signaling pathway (IIS) is a highly conserved signaling pathway in animals and is central to mediating organismal responses to nutrients (Hietakangas and Cohen 2009; Grewal 2009).” (Myers et al., 2024). “D. ananassae (NCBI:txid7217) is part of the melanogaster species group within the subgenus Sophophora of the genus Drosophila (Sturtevant 1939; Bock and Wheeler 1972). It was first described by Doleschall (1858). D. ananassae is circumtropical (Markow and O'Grady 2005; https://www.taxodros.uzh.ch, accessed 1 Feb 2023), and often associated with human settlement (Singh 2010). It has been extensively studied as a model for its cytogenetic and genetic characteristics, and in experimental evolution (Kikkawa 1938; Singh and Yadav 2015).” (Lawson et al., submitted). |
We propose a gene model for the Drosophila ananassae ortholog of the D. melanogaster Protein tyrosine phosphatase 61F (Ptp61F) gene. The genomic region of the ortholog corresponds to the uncharacterized protein XP_014764155.1 (Locus ID LOC6492936) in the May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly of Drosophila ananassae (GCA_000005115.1 - Graveley et al., 2011). This model is based on RNA-Seq data from Drosophila ananassae (SRP006203, SRP007906, PRJNA257286, PRJNA388952) and Ptp61F in D. melanogaster using FlyBase release FB2023_03 (GCA_000001215.4) (Larkin et al., 2021; Gramates et al., 2022).
The protein product of Ptp61F (PTP61) negatively regulates the Insulin/TOR pathway by dephosphorylating the insulin receptor (InR) (Wu et al., 2011; Buszard et al., 2013). PTP61Fm-mediated dephosphorylation of InR requires an interaction with the SH2/SH3 adaptor protein Dock (dreadlocks) while PTP61Fn dephosphorylates InR in a Dock-independent manner (Clemens et al., 1996; Buszard et al., 2013; Willoughby et al., 2017). The Ptp61F gene in Drosophila melanogaster was first isolated using rat PTP61F cDNA in a low stringency hybridization screening method (McLaughlin and Dixon 1993). Ptp61F is differentially spliced where the longer isoform (PTP61Fm) is targeted to the ER by the hydrophobic C-terminal domain, and the shorter isoform (PTP61Fn) is targeted to the nucleus by a nuclear localization signal (NLS) (McLaughlin and Dixon 1993). PTP61F plays a role in the regulation of a variety of signaling pathways through negative regulation of tyrosine kinases including Janus kinase/signal transducers and activators of transcription (JAK/STAT), Mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR), and platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) (Baeg et al., 2005; Buszard et al., 2013; Tchankouo-Nguetcheu et al., 2014; Willoughby et al., 2017).
Species details can be found in the description above.
Synteny
The target gene, Ptp61F, occurs on chromosome 3L in D. melanogaster and is flanked upstream by rhomboid (rho) and Stromalin 2 (SA2) and downstream by indra and Hydroxymethylbilane synthase (Hmbs). There are also 6 genes nested within Ptp61F in D. melanogaster: CG9173, FucTD, CG9168, CG32320, ru, and CG9166. The tblastn search of D. melanogaster Ptp61F-PA (query) against the Drosophila ananassae (GenBank Accession: GCA_000005115.1) Genome Assembly (database) placed the putative ortholog of Ptp61F within scaffold_13337 at locus LOC6492936 (XP_014764155.1)— with an E-value of 7e-28 and a percent identity of 84.48%. Furthermore, the putative ortholog is flanked upstream by LOC6492935 (XP_001956685.1) and LOC6507090 (XP_001956686.1), which correspond to Reg2 and CG9166 in D. melanogaster (E-value: 0.0 and 2e-140; identity: 89.62% and 83.55%, respectively, as determined by blastp) (Figure 1A; Altschul et al., 1990). The putative ortholog of Ptp61F is flanked downstream by LOC6492937 (XP_ 001956688.1) and LOC6507089 (XP_ 001956689.1), which correspond to indra and Hmbs in D. melanogaster (E-value: 2e-96 and 0.0; identity: 32.20% and 86.85%, respectively, as determined by blastp). The putative ortholog assignment for Ptp61F in Drosophila ananassae is supported by the following evidence: The blastpand tblastn results support the presence of a Ptp61F ortholog in this location in D. ananassae although synteny is not completely conserved. In D. melanogaster, the Ptp61F-PC isoform has 6 genes nested within it, but this characteristic is not present in D. ananassae, so we hypothesize that the Ptp61F-PC isoform does not exist in this species. CG9166 is present in both genomic neighborhoods, but in slightly different locations (i.e., not nested within Ptp61F), and the first and second downstream genes (indra and Hmbs) are orthologous. Therefore, we conclude that LOC6492936 is the correct ortholog of Ptp61F in D. ananassae (Figure 1A).
Protein Model
Ptp61F in D. melanogaster has five protein-coding isoforms: Ptp61F-PA, Ptp61F-PB, Ptp61F-PC, Ptp61F-PD, and Ptp61F-PE. Ptp61F-PE and Ptp61F-PD have identical coding sequences. mRNA soform Ptp61F-RA contains six protein-coding CDSs, Ptp61F-RB and Ptp61F-RC have seven protein-coding CDSs, and Ptp61F-RD and Ptp61F-RE have four protein-coding CDSs. In D. ananassae, the isoform count is not conserved (see Special characteristics of the protein model), and we predict five total isoforms (Ptp61F-PA, Ptp61F-PB, Ptp61F-PD, Ptp61F-PE,and Ptp61F-PNF). The sequence of Ptp61F-PA in Drosophila ananassae has 76.87% identity (E-value: 0.0) with the protein-coding isoform Ptp61F-PA in D. melanogaster, as determined by blastp (Figure 1C). Coordinates of this curated gene model are stored by NCBI at GenBank/BankIt (accessions BK064622, BK064623, BK064624, BK064625, and BK064626). These data are also archived in the CaltechDATA repository (see “Extended Data” section below).
Special characteristics of the protein model
We hypothesize that the isoform Ptp61F-RC does not exist in D. ananassae. In addition, we hypothesize that there is a new isoform, Ptp61F-RNF, due to alternative splicing. Ptp61F-RC in D. melanogaster has a long first intron that has six genes nested within it, but this does not appear in D. ananassae (Figure 1A). A tblastn search of the amino acid sequence of the first CDS in Ptp61F-RC in D. melanogaster against the D. ananassae genome did not return any results, and there are no predicted splice junctions consistent with a long first intron for Ptp61F-RC in this species. This leads us to conclude that the Ptp61F-RC isoform is not present in D. ananassae. Finally, we determined that XM_032453921 (LOC6492936) is a novel isoform, as there is not an orthologous isoform in D. melanogaster that has the same gene structure. It has seven protein-coding CDSs, and its sixth CDS is longer than the corresponding CDS in isoform Ptp61F-RB (Figure 1D).The seventh CDS of the proposed novel isoform is only eight base pairs long (including the stop codon), as compared to 37 base pairs long for the seventh CDS of isoform Ptp61F-RB. The sixth and seventh CDSs of this novel isoform are supported by a splice junction with a score of 457 (Figure 1D, shown in pink). These features of XM_032453921 (LOC6492936) lead us to believe that alternative splicing has occurred, resulting in a novel isoform. We propose that this isoform be named Ptp61F-RNF.
","references":[{"reference":"Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. J Mol Biol 215(3): 403-10.
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","pubmedId":"21707536","doi":""}],"title":"Gene model for the ortholog of Ptp61F in Drosophila ananassae
","reviews":[{"reviewer":{"displayName":"Melanie Van Stry"},"openAcknowledgement":false,"status":{"submitted":true}}],"curatorReviews":[{"curator":{"displayName":"FlyBase Curators"},"openAcknowledgement":false,"submitted":null}]},{"id":"37899d6a-7fcf-4e70-a8c9-5349a483f208","decision":"accept","abstract":"Gene model for the ortholog of Protein tyrosine phosphatase 61F (Ptp61F) in the Drosophila ananassae May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly (GenBank Accession: GCA_000005115.1). This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.
","acknowledgements":"We would like to thank Wilson Leung for developing and maintaining the technological infrastructure that was used to create this gene model. Thank you to FlyBase for providing the definitive database for Drosophila melanogaster gene models.
","authors":[{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","validation","writing_originalDraft","writing_reviewEditing"],"email":"aebacklund@crimson.ua.edu","firstName":"Anne E.","lastName":"Backlund","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0003-2494-2388"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["dataCuration","validation","visualization","writing_reviewEditing"],"email":"lcohen5@worcester.edu","firstName":"Logan","lastName":"Cohen","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-2961-0334"},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"priyav1129@gmail.com","firstName":"Priya","lastName":"Vaid","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0001-8770-9589"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"chloenason@icloud.com","firstName":"Chloe","lastName":"Nason","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"kfkneuper@gmail.com","firstName":"Kara","lastName":"Kneuper","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"ajademiller13@gmail.com","firstName":"Ali Jade","lastName":"Miller","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"chris.ellison@rutgers.edu","firstName":"Christopher E.","lastName":"Ellison","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-0350-0962"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"lindsey.long@oc.edu","firstName":"Lindsey J.","lastName":"Long","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4524-9307"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["writing_originalDraft"],"email":"dbarnard@worcester.edu","firstName":"Daron","lastName":"Barnard","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["dataCuration","formalAnalysis","methodology","project","software","supervision","validation","visualization","writing_reviewEditing"],"email":"gep@ua.edu","firstName":"Chinmay P.","lastName":"Rele","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-3473-9319"},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["supervision","writing_reviewEditing","conceptualization","fundingAcquisition","methodology","project"],"email":"lreed1@ua.edu","firstName":"Laura K.","lastName":"Reed","submittingAuthor":true,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4381-494X"}],"awards":[{"awardId":"R25GM130517","funderName":"National Institutes of Health (United States)","awardRecipient":"Laura K Reed"},{"awardId":"1915544","funderName":"National Science Foundation (United States)","awardRecipient":"Laura K Reed"}],"conflictsOfInterest":"The authors declare that there are no conflicts of interest present.
","dataTable":{"url":null},"extendedData":[{"description":"Zip file containing FASTA, PEP, and GFF","doi":"10.22002/7tpn6-87t55","resourceType":"Model","name":"DanaCAF1_Ptp62F.zip","url":"https://portal.micropublication.org/uploads/7a855675834516099ae5ba647e373621.zip"}],"funding":"This material is based upon work supported by the National Science Foundation under Grant No. IUSE-1915544 to LKR and the National Institute of General Medical Sciences of the National Institutes of Health Award R25GM130517 to LKR. The Genomics Education Partnership is fully financed by Federal moneys. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
","image":{"url":"https://portal.micropublication.org/uploads/5c2c56a29d3f844c92e535f9e35b6955.png"},"imageCaption":"(A) Synteny comparison of the genomic neighborhoods for Ptp61F in Drosophila melanogaster and Drosophila ananassae. Thin underlying arrows indicate the DNA strand within which the gene–Ptp61F–is located in D. melanogaster (top) and D. ananassae (bottom). The thin arrow pointing to the right indicates that Ptp61F is on the positive (+) strand in Drosophila ananassae, and the thin arrow pointing to the left indicates that Ptp61F is on the negative (-) strand in D. melanogaster. The wide gene arrows pointing in the same direction as Ptp61F are on the same strand relative to the thin underlying arrows, while wide gene arrows pointing in the opposite direction of Ptp61F are on the opposite strand relative to the thin underlying arrows. White gene arrows in Drosophila ananassae indicate orthology to the corresponding gene in D. melanogaster, while black gene arrows indicate non-orthology. Gene symbols given in the Drosophila ananassae gene arrows indicate the orthologous gene in D. melanogaster, while the locus identifiers are specific to Drosophila ananassae. (B) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The coding-regions of Ptp61F in Drosophila ananassae are displayed in the User Supplied Track (black); coding CDSs are depicted by thick rectangles and introns by thin lines with arrows indicating the direction of transcription. Subsequent evidence tracks include BLAT Alignments of NCBI RefSeq Genes (dark blue, alignment of Ref-Seq genes for Drosophila ananassae), Spaln of D. melanogaster Proteins (purple, alignment of Ref-Seq proteins from D. melanogaster), Transcripts and Coding Regions Predicted by TransDecoder (dark green), RNA-Seq from Adult Females, Adult Males, and Wolbachia-cured Embryos (red, light blue, and pink, respectively; alignment of Illumina RNA-Seq reads from Drosophila ananassae), and Splice Junctions Predicted by regtools using Drosophila ananassae RNA-Seq (SRP006203, SRP007906, PRJNA257286, PRJNA388952). Splice junctions shown have a minimum read-depth of 10 with 50-99, 100-499, 500-999, >1000 supporting reads in green, pink, brown, and red, respectively. (C) Dot Plot of Ptp61F-PA in D. melanogaster (x-axis) vs. the orthologous peptide in Drosophila ananassae (y-axis). Amino acid number is indicated along the left and bottom; coding-CDS number is indicated along the top and right, and CDSs are also highlighted with alternating colors. Line breaks in the dot plot indicate mismatching amino acids at the specified location between species. (D) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The same evidence tracks as Figure 1B are shown in this image. We hypothesize that the isoform Ptp61F-PC does not exist in D. ananassae. In addition, we hypothesize that there is a novel isoform, Ptp61F-PNF.
","imageTitle":"Genomic neighborhoods for Ptp61F in Drosophila melanogaster and Drosophila ananassae
","methods":"Detailed methods including algorithms, database versions, and citations for the complete annotation process can be found in Rele et al. (2023). Briefly, students use the GEP instance of the UCSC Genome Browser v.435 (https://gander.wustl.edu; Kent WJ et al., 2002; Navarro Gonzalez et al., 2021) to examine the genomic neighborhood of their reference IIS gene in the D. melanogaster genome assembly (Aug. 2014; BDGP Release 6 + ISO1 MT/dm6). Students then retrieve the protein sequence for the D. melanogaster reference gene for a given isoform and run it using tblastn against their target Drosophila species genome assembly on the NCBI BLAST server (https://blast.ncbi.nlm.nih.gov/Blast.cgi; Altschul et al., 1990) to identify potential orthologs. To validate the potential ortholog, students compare the local genomic neighborhood of their potential ortholog with the genomic neighborhood of their reference gene in D. melanogaster. This local synteny analysis includes at minimum the two upstream and downstream genes relative to their putative ortholog. They also explore other sets of genomic evidence using multiple alignment tracks in the Genome Browser, including BLAT alignments of RefSeq Genes, Spaln alignment of D. melanogaster proteins, multiple gene prediction tracks (e.g., GeMoMa, Geneid, Augustus), and modENCODE RNA-Seq from the target species. Detailed explanation of how these lines of genomic evidenced are leveraged by students in gene model development are described in Rele et al. (2023). Genomic structure information (e.g., CDSs, intron-exon number and boundaries, number of isoforms) for the D. melanogaster reference gene is retrieved through the Gene Record Finder (https://gander.wustl.edu/~wilson/dmelgenerecord/index.html; Rele et al., 2023). Approximate splice sites within the target gene are determined using tblastn using the CDSs from the D. melanogaster reference gene. Coordinates of CDSs are then refined by examining aligned modENCODE RNA-Seq data, and by applying paradigms of molecular biology such as identifying canonical splice site sequences and ensuring the maintenance of an open reading frame across hypothesized splice sites. Students then confirm the biological validity of their target gene model using the Gene Model Checker (https://gander.wustl.edu/~wilson/genechecker/index.html; Rele et al., 2023), which compares the structure and translated sequence from their hypothesized target gene model against the D. melanogaster reference gene model. At least two independent models for a gene are generated by students under mentorship of their faculty course instructors. Those models are then reconciled by a third independent researcher mentored by the project leaders to produce the final model. Note: comparison of 5' and 3' UTR sequence information is not included in this GEP CURE protocol (Gruys et al., 2025).
","reagents":"","patternDescription":"This article reports a predicted gene model generated by undergraduate work using a structured gene model annotation protocol defined by the Genomics Education Partnership (GEP; thegep.org) for Course-based Undergraduate Research Experience (CURE). The following information in this box may be repeated in other articles submitted by participants using the same GEP CURE protocol for annotating Drosophila species orthologs of Drosophila melanogaster genes in the insulin signaling pathway. \"In this GEP CURE protocol students use web-based tools to manually annotate genes in non-model Drosophila species based on orthology to genes in the well-annotated model organism fruitfly Drosophila melanogaster. The GEP uses web-based tools to allow undergraduates to participate in course-based research by generating manual annotations of genes in non-model species (Rele et al., 2023). Computational-based gene predictions in any organism are often improved by careful manual annotation and curation, allowing for more accurate analyses of gene and genome evolution (Mudge and Harrow 2016; Tello-Ruiz et al., 2019). These models of orthologous genes across species, such as the one presented here, then provide a reliable basis for further evolutionary genomic analyses when made available to the scientific community.” (Myers et al., 2024). “The particular gene ortholog described here was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila. The Insulin/insulin-like growth factor signaling pathway (IIS) is a highly conserved signaling pathway in animals and is central to mediating organismal responses to nutrients (Hietakangas and Cohen 2009; Grewal 2009).” (Myers et al., 2024). “D. ananassae (NCBI:txid7217) is part of the melanogaster species group within the subgenus Sophophora of the genus Drosophila (Sturtevant 1939; Bock and Wheeler 1972). It was first described by Doleschall (1858). D. ananassae is circumtropical (Markow and O'Grady 2005; https://www.taxodros.uzh.ch, accessed 1 Feb 2023), and often associated with human settlement (Singh 2010). It has been extensively studied as a model for its cytogenetic and genetic characteristics, and in experimental evolution (Kikkawa 1938; Singh and Yadav 2015).” (Lawson et al., 2024). |
We propose a gene model for the Drosophila ananassae ortholog of the D. melanogaster Protein tyrosine phosphatase 61F (Ptp61F) gene. The genomic region of the ortholog corresponds to the uncharacterized protein XP_014764155.1 (Locus ID LOC6492936) in the May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly of Drosophila ananassae (GCA_000005115.1, Drosophila 12 Genomes Consortium et al., 2007). This model is based on RNA-Seq data from Drosophila ananassae (SRP006203, SRP007906, PRJNA257286, PRJNA388952; Graveley et al., 2011) and Ptp61F in D. melanogaster using FlyBase release FB2023_03 (GCA_000001215.4) (Larkin et al., 2021; Gramates et al., 2022; Jenkins et al., 2022).
The protein product of Ptp61F (PTP61) negatively regulates the Insulin/TOR pathway by dephosphorylating the insulin receptor (InR) (Wu et al., 2011; Buszard et al., 2013). PTP61Fm-mediated dephosphorylation of InR requires an interaction with the SH2/SH3 adaptor protein Dock (dreadlocks) while PTP61Fn dephosphorylates InR in a Dock-independent manner (Clemens et al., 1996; Buszard et al., 2013; Willoughby et al., 2017). The Ptp61F gene in Drosophila melanogaster was first isolated using rat PTP61F cDNA in a low stringency hybridization screening method (McLaughlin and Dixon 1993). Ptp61F is differentially spliced where the longer isoform (PTP61Fm) is targeted to the ER by the hydrophobic C-terminal domain, and the shorter isoform (PTP61Fn) is targeted to the nucleus by a nuclear localization signal (NLS) (McLaughlin and Dixon 1993). PTP61F plays a role in the regulation of a variety of signaling pathways through negative regulation of tyrosine kinases including Janus kinase/signal transducers and activators of transcription (JAK/STAT), Mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR), and platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) (Baeg et al., 2005; Buszard et al., 2013; Tchankouo-Nguetcheu et al., 2014; Willoughby et al., 2017).
Synteny
The reference gene, Ptp61F, occurs on chromosome 3L in D. melanogaster and is flanked upstream by rhomboid (rho) and Stromalin 2 (SA2) and downstream by indra and Hydroxymethylbilane synthase (Hmbs). There are also six genes nested within Ptp61F in D. melanogaster: CG9173, FucTD, CG9168, CG32320, ru, and CG9166. The tblastn search of D. melanogaster Ptp61F-PA (query) against the Drosophila ananassae (GenBank Accession: GCA_000005115.1) Genome Assembly (database) placed the putative ortholog of Ptp61F within scaffold_13337 at locus LOC6492936 (XP_014764155.1)— with an E-value of 7e-28 and a percent identity of 84.48%. Furthermore, the putative ortholog is flanked upstream by LOC6492935 (XP_001956685.1) and LOC6507090 (XP_001956686.1), which correspond to Reg-2 and CG9166 in D. melanogaster (E-value: 0.0 and 2e-140; identity: 89.62% and 83.55%, respectively, as determined by blastp) (Figure 1A; Altschul et al., 1990). The putative ortholog of Ptp61F is flanked downstream by LOC6492937 (XP_ 001956688.1) and LOC6507089 (XP_ 001956689.1), which correspond to indra and Hmbs in D. melanogaster (E-value: 2e-96 and 0.0; identity: 32.20% and 86.85%, respectively, as determined by blastp). The putative ortholog assignment for Ptp61F in D. ananassae is supported by the following evidence: The blastp and tblastn results support the presence of a Ptp61F ortholog in this location in D. ananassae although synteny is not completely conserved. In D. melanogaster, the Ptp61F-PC isoform has 6 genes nested within it, but this characteristic is not present in D. ananassae, so we hypothesize that the Ptp61F-PC isoform does not exist in this species. CG9166 is present in both genomic neighborhoods, but in slightly different locations (i.e., not nested within Ptp61F), and the first and second downstream genes (indra and Hmbs) are orthologous. Therefore, we conclude that LOC6492936 is the correct ortholog of Ptp61F in D. ananassae (Figure 1A).
Protein Model
Ptp61F in D. melanogaster has mRNA isoforms: Ptp61F-RA, Ptp61F-RB, Ptp61F-RC, Ptp61F-RD, and Ptp61F-RE. Ptp61F-RE and Ptp61F-RD have identical coding sequences. mRNA soform Ptp61F-RA contains six CDSs, Ptp61F-RB and Ptp61F-RC have seven CDSs, and Ptp61F-RD and Ptp61F-RE have four CDSs. In D. ananassae, the isoform count is not conserved (see Special characteristics of the protein model), and we predict five total isoforms (Ptp61F-PA, Ptp61F-PB, Ptp61F-PD, Ptp61F-PE,and Ptp61F-PNF). The sequence of Ptp61F-PA in Drosophila ananassae has 76.87% identity (E-value: 0.0) with the protein-coding isoform Ptp61F-PA in D. melanogaster, as determined by blastp (Figure 1C). Given that D. ananassae and D. melanogaster belong to distinct species groups, the observed degree protein divergence is well explained and consistent with that seen in other ortholog comparisons between these two species (Drosophila 12 Genomes Consortium et al., 2007). Coordinates of this curated gene model are stored by NCBI at GenBank/BankIt (accessions BK064622, BK064623, BK064624, BK064625, and BK064626). These data are also archived in the CaltechDATA repository (see “Extended Data” section below).
Special characteristics of the protein model
We hypothesize that the isoform Ptp61F-PC does not exist in D. ananassae. In addition, we hypothesize that there is a new isoform, Ptp61F-PNF, due to alternative splicing. Ptp61F-PC in D. melanogaster has a long first intron that has six genes nested within it, but this does not appear in D. ananassae (Figure 1A). A tblastn search of the amino acid sequence of the first CDS in Ptp61F-PC in D. melanogaster against the D. ananassae genome did not return any results, and there are no predicted splice junctions consistent with a long first intron for Ptp61F-PC in this species. This leads us to conclude that the Ptp61F-PC isoform is not present in D. ananassae. Finally, we determined that XM_032453921 (LOC6492936) is a novel isoform, as there is not an orthologous isoform in D. melanogaster that has the same gene structure. It has seven CDSs, and its sixth CDS is longer than the corresponding CDS in isoform Ptp61F-PB (Figure 1D). The seventh CDS of the proposed novel isoform is only eight base pairs long (including the stop codon), as compared to 37 base pairs long for the seventh CDS of isoform Ptp61F-RB. The sixth and seventh CDSs of this novel isoform are supported by a splice junction with a score of 457 (Figure 1D, shown in pink). These features of XM_032453921 (LOC6492936) lead us to believe that new alternative splicing has occurred, resulting in a novel isoform. This novel isoform has 75.86% protein identity (E-value: 0.0) to the D. melanogaster Ptp61F-PB isoform. We propose that this isoform be named Ptp61F-PNF.
","references":[{"reference":"Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. J Mol Biol 215(3): 403-10.
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","pubmedId":"21707536","doi":""}],"title":"Gene model for the ortholog of Ptp61F in Drosophila ananassae
","reviews":[],"curatorReviews":[{"curator":{"displayName":"FlyBase Curators"},"openAcknowledgement":false,"submitted":"1783059988502"}]},{"id":"094bd9c3-4e20-474c-89f8-cb987713c680","decision":"publish","abstract":"Gene model for the ortholog of Protein tyrosine phosphatase 61F (Ptp61F) in the Drosophila ananassae May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly (GenBank Accession: GCA_000005115.1). This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.
","acknowledgements":"We would like to thank Wilson Leung for developing and maintaining the technological infrastructure that was used to create this gene model. Thank you to FlyBase for providing the definitive database for Drosophila melanogaster gene models.
","authors":[{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","validation","writing_originalDraft","writing_reviewEditing"],"email":"aebacklund@crimson.ua.edu","firstName":"Anne E.","lastName":"Backlund","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0003-2494-2388"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["dataCuration","validation","visualization","writing_reviewEditing"],"email":"lcohen5@worcester.edu","firstName":"Logan","lastName":"Cohen","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-2961-0334"},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"priyav1129@gmail.com","firstName":"Priya","lastName":"Vaid","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0001-8770-9589"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"chloenason@icloud.com","firstName":"Chloe","lastName":"Nason","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"kfkneuper@gmail.com","firstName":"Kara","lastName":"Kneuper","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["formalAnalysis","writing_reviewEditing"],"email":"ajademiller13@gmail.com","firstName":"Ali Jade","lastName":"Miller","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["Rutgers University, New Brunswick, NJ USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"chris.ellison@rutgers.edu","firstName":"Christopher E.","lastName":"Ellison","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-0350-0962"},{"affiliations":["Oklahoma Christian University, Edmond, OK USA"],"departments":[""],"credit":["supervision","writing_reviewEditing"],"email":"lindsey.long@oc.edu","firstName":"Lindsey J.","lastName":"Long","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4524-9307"},{"affiliations":["Worcester State University, Worcester MA, USA"],"departments":[""],"credit":["writing_originalDraft"],"email":"dbarnard@worcester.edu","firstName":"Daron","lastName":"Barnard","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":""},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["dataCuration","formalAnalysis","methodology","project","software","supervision","validation","visualization","writing_reviewEditing"],"email":"gep@ua.edu","firstName":"Chinmay P.","lastName":"Rele","submittingAuthor":false,"correspondingAuthor":false,"equalContribution":false,"WBId":null,"orcid":"0000-0002-3473-9319"},{"affiliations":["The University of Alabama, Tuscaloosa, AL USA"],"departments":[""],"credit":["supervision","writing_reviewEditing","conceptualization","fundingAcquisition","methodology","project"],"email":"lreed1@ua.edu","firstName":"Laura K.","lastName":"Reed","submittingAuthor":true,"correspondingAuthor":true,"equalContribution":false,"WBId":null,"orcid":"0000-0002-4381-494X"}],"awards":[{"awardId":"R25GM130517","funderName":"National Institutes of Health (United States)","awardRecipient":"LK Reed"},{"awardId":"1915544","funderName":"National Science Foundation (United States)","awardRecipient":"LK Reed"}],"conflictsOfInterest":"The authors declare that there are no conflicts of interest present.
","dataTable":{"url":null},"extendedData":[{"description":"Zip file containing FASTA, PEP, and GFF","doi":"10.22002/7tpn6-87t55","resourceType":"Model","name":"DanaCAF1_Ptp62F.zip","url":"https://portal.micropublication.org/uploads/7a855675834516099ae5ba647e373621.zip"}],"funding":"This material is based upon work supported by the National Science Foundation under Grant No. IUSE-1915544 to LKR and the National Institute of General Medical Sciences of the National Institutes of Health Award R25GM130517 to LKR. The Genomics Education Partnership is fully financed by Federal moneys. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
","image":{"url":"https://portal.micropublication.org/uploads/5c2c56a29d3f844c92e535f9e35b6955.png"},"imageCaption":"(A) Synteny comparison of the genomic neighborhoods for Ptp61F in Drosophila melanogaster and Drosophila ananassae. Thin underlying arrows indicate the DNA strand within which the gene–Ptp61F–is located in D. melanogaster (top) and D. ananassae (bottom). The thin arrow pointing to the right indicates that Ptp61F is on the positive (+) strand in Drosophila ananassae, and the thin arrow pointing to the left indicates that Ptp61F is on the negative (-) strand in D. melanogaster. The wide gene arrows pointing in the same direction as Ptp61F are on the same strand relative to the thin underlying arrows, while wide gene arrows pointing in the opposite direction of Ptp61F are on the opposite strand relative to the thin underlying arrows. White gene arrows in Drosophila ananassae indicate orthology to the corresponding gene in D. melanogaster, while black gene arrows indicate non-orthology. Gene symbols given in the Drosophila ananassae gene arrows indicate the orthologous gene in D. melanogaster, while the locus identifiers are specific to Drosophila ananassae. (B) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The coding-regions of Ptp61F in Drosophila ananassae are displayed in the User Supplied Track (black); coding CDSs are depicted by thick rectangles and introns by thin lines with arrows indicating the direction of transcription. Subsequent evidence tracks include BLAT Alignments of NCBI RefSeq Genes (dark blue, alignment of Ref-Seq genes for Drosophila ananassae), Spaln of D. melanogaster Proteins (purple, alignment of Ref-Seq proteins from D. melanogaster), Transcripts and Coding Regions Predicted by TransDecoder (dark green), RNA-Seq from Adult Females, Adult Males, and Wolbachia-cured Embryos (red, light blue, and pink, respectively; alignment of Illumina RNA-Seq reads from Drosophila ananassae), and Splice Junctions Predicted by regtools using Drosophila ananassae RNA-Seq (SRP006203, SRP007906, PRJNA257286, PRJNA388952). Splice junctions shown have a minimum read-depth of 10 with 50-99, 100-499, 500-999, >1000 supporting reads in green, pink, brown, and red, respectively. (C) Dot Plot of Ptp61F-PA in D. melanogaster (x-axis) vs. the orthologous peptide in Drosophila ananassae (y-axis). Amino acid number is indicated along the left and bottom; coding-CDS number is indicated along the top and right, and CDSs are also highlighted with alternating colors. Line breaks in the dot plot indicate mismatching amino acids at the specified location between species. (D) Gene Model in GEP UCSC Track Data Hub (Raney et al., 2014). The same evidence tracks as Figure 1B are shown in this image. We hypothesize that the isoform Ptp61F-PC does not exist in D. ananassae. In addition, we hypothesize that there is a novel isoform, Ptp61F-PNF.
","imageTitle":"Genomic neighborhoods for Ptp61F in Drosophila melanogaster and Drosophila ananassae
","methods":"Detailed methods including algorithms, database versions, and citations for the complete annotation process can be found in Rele et al. (2023). Briefly, students use the GEP instance of the UCSC Genome Browser v.435 (https://gander.wustl.edu; Kent WJ et al., 2002; Navarro Gonzalez et al., 2021) to examine the genomic neighborhood of their reference IIS gene in the D. melanogaster genome assembly (Aug. 2014; BDGP Release 6 + ISO1 MT/dm6). Students then retrieve the protein sequence for the D. melanogaster reference gene for a given isoform and run it using tblastn against their target Drosophila species genome assembly on the NCBI BLAST server (https://blast.ncbi.nlm.nih.gov/Blast.cgi; Altschul et al., 1990) to identify potential orthologs. To validate the potential ortholog, students compare the local genomic neighborhood of their potential ortholog with the genomic neighborhood of their reference gene in D. melanogaster. This local synteny analysis includes at minimum the two upstream and downstream genes relative to their putative ortholog. They also explore other sets of genomic evidence using multiple alignment tracks in the Genome Browser, including BLAT alignments of RefSeq Genes, Spaln alignment of D. melanogaster proteins, multiple gene prediction tracks (e.g., GeMoMa, Geneid, Augustus), and modENCODE RNA-Seq from the target species. Detailed explanation of how these lines of genomic evidenced are leveraged by students in gene model development are described in Rele et al. (2023). Genomic structure information (e.g., CDSs, intron-exon number and boundaries, number of isoforms) for the D. melanogaster reference gene is retrieved through the Gene Record Finder (https://gander.wustl.edu/~wilson/dmelgenerecord/index.html; Rele et al., 2023). Approximate splice sites within the target gene are determined using tblastn using the CDSs from the D. melanogaster reference gene. Coordinates of CDSs are then refined by examining aligned modENCODE RNA-Seq data, and by applying paradigms of molecular biology such as identifying canonical splice site sequences and ensuring the maintenance of an open reading frame across hypothesized splice sites. Students then confirm the biological validity of their target gene model using the Gene Model Checker (https://gander.wustl.edu/~wilson/genechecker/index.html; Rele et al., 2023), which compares the structure and translated sequence from their hypothesized target gene model against the D. melanogaster reference gene model. At least two independent models for a gene are generated by students under mentorship of their faculty course instructors. Those models are then reconciled by a third independent researcher mentored by the project leaders to produce the final model. Note: comparison of 5' and 3' UTR sequence information is not included in this GEP CURE protocol (Gruys et al., 2025).
","reagents":"","patternDescription":"This article reports a predicted gene model generated by undergraduate work using a structured gene model annotation protocol defined by the Genomics Education Partnership (GEP; thegep.org) for Course-based Undergraduate Research Experience (CURE). The following information in this box may be repeated in other articles submitted by participants using the same GEP CURE protocol for annotating Drosophila species orthologs of Drosophila melanogaster genes in the insulin signaling pathway. \"In this GEP CURE protocol students use web-based tools to manually annotate genes in non-model Drosophila species based on orthology to genes in the well-annotated model organism fruitfly Drosophila melanogaster. The GEP uses web-based tools to allow undergraduates to participate in course-based research by generating manual annotations of genes in non-model species (Rele et al., 2023). Computational-based gene predictions in any organism are often improved by careful manual annotation and curation, allowing for more accurate analyses of gene and genome evolution (Mudge and Harrow 2016; Tello-Ruiz et al., 2019). These models of orthologous genes across species, such as the one presented here, then provide a reliable basis for further evolutionary genomic analyses when made available to the scientific community.” (Myers et al., 2024). “The particular gene ortholog described here was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila. The Insulin/insulin-like growth factor signaling pathway (IIS) is a highly conserved signaling pathway in animals and is central to mediating organismal responses to nutrients (Hietakangas and Cohen 2009; Grewal 2009).” (Myers et al., 2024). “D. ananassae (NCBI:txid7217) is part of the melanogaster species group within the subgenus Sophophora of the genus Drosophila (Sturtevant 1939; Bock and Wheeler 1972). It was first described by Doleschall (1858). D. ananassae is circumtropical (Markow and O'Grady 2005; https://www.taxodros.uzh.ch, accessed 1 Feb 2023), and often associated with human settlement (Singh 2010). It has been extensively studied as a model for its cytogenetic and genetic characteristics, and in experimental evolution (Kikkawa 1938; Singh and Yadav 2015).” (Lawson et al., 2024). |
We propose a gene model for the Drosophila ananassae ortholog of the D. melanogaster Protein tyrosine phosphatase 61F (Ptp61F) gene. The genomic region of the ortholog corresponds to the uncharacterized protein XP_014764155.1 (Locus ID LOC6492936) in the May 2011 (Agencourt dana_caf1/DanaCAF1) Genome Assembly of Drosophila ananassae (GCA_000005115.1, Drosophila 12 Genomes Consortium et al., 2007). This model is based on RNA-Seq data from Drosophila ananassae (SRP006203, SRP007906, PRJNA257286, PRJNA388952; Graveley et al., 2011) and Ptp61F in D. melanogaster using FlyBase release FB2023_03 (GCA_000001215.4) (Larkin et al., 2021; Gramates et al., 2022; Jenkins et al., 2022).
The protein product of Ptp61F (PTP61) negatively regulates the Insulin/TOR pathway by dephosphorylating the insulin receptor (InR) (Wu et al., 2011; Buszard et al., 2013). PTP61Fm-mediated dephosphorylation of InR requires an interaction with the SH2/SH3 adaptor protein Dock (dreadlocks) while PTP61Fn dephosphorylates InR in a Dock-independent manner (Clemens et al., 1996; Buszard et al., 2013; Willoughby et al., 2017). The Ptp61F gene in Drosophila melanogaster was first isolated using rat PTP61F cDNA in a low stringency hybridization screening method (McLaughlin and Dixon 1993). Ptp61F is differentially spliced where the longer isoform (PTP61Fm) is targeted to the ER by the hydrophobic C-terminal domain, and the shorter isoform (PTP61Fn) is targeted to the nucleus by a nuclear localization signal (NLS) (McLaughlin and Dixon 1993). PTP61F plays a role in the regulation of a variety of signaling pathways through negative regulation of tyrosine kinases including Janus kinase/signal transducers and activators of transcription (JAK/STAT), Mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR), and platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) (Baeg et al., 2005; Buszard et al., 2013; Tchankouo-Nguetcheu et al., 2014; Willoughby et al., 2017).
Synteny
The reference gene, Ptp61F, occurs on chromosome 3L in D. melanogaster and is flanked upstream by rhomboid (rho) and Stromalin 2 (SA2) and downstream by indra and Hydroxymethylbilane synthase (Hmbs). There are also six genes nested within Ptp61F in D. melanogaster: CG9173, FucTD, CG9168, CG32320, ru, and CG9166. The tblastn search of D. melanogaster Ptp61F-PA (query) against the Drosophila ananassae (GenBank Accession: GCA_000005115.1) Genome Assembly (database) placed the putative ortholog of Ptp61F within scaffold_13337 at locus LOC6492936 (XP_014764155.1)— with an E-value of 7e-28 and a percent identity of 84.48%. Furthermore, the putative ortholog is flanked upstream by LOC6492935 (XP_001956685.1) and LOC6507090 (XP_001956686.1), which correspond to Reg-2 and CG9166 in D. melanogaster (E-value: 0.0 and 2e-140; identity: 89.62% and 83.55%, respectively, as determined by blastp) (Figure 1A; Altschul et al., 1990). The putative ortholog of Ptp61F is flanked downstream by LOC6492937 (XP_ 001956688.1) and LOC6507089 (XP_ 001956689.1), which correspond to indra and Hmbs in D. melanogaster (E-value: 2e-96 and 0.0; identity: 32.20% and 86.85%, respectively, as determined by blastp). The putative ortholog assignment for Ptp61F in D. ananassae is supported by the following evidence: The blastp and tblastn results support the presence of a Ptp61F ortholog in this location in D. ananassae although synteny is not completely conserved. In D. melanogaster, the Ptp61F-PC isoform has 6 genes nested within it, but this characteristic is not present in D. ananassae, so we hypothesize that the Ptp61F-PC isoform does not exist in this species. CG9166 is present in both genomic neighborhoods, but in slightly different locations (i.e., not nested within Ptp61F), and the first and second downstream genes (indra and Hmbs) are orthologous. Therefore, we conclude that LOC6492936 is the correct ortholog of Ptp61F in D. ananassae (Figure 1A).
Protein Model
Ptp61F in D. melanogaster has mRNA isoforms: Ptp61F-RA, Ptp61F-RB, Ptp61F-RC, Ptp61F-RD, and Ptp61F-RE. Ptp61F-RE and Ptp61F-RD have identical coding sequences. mRNA soform Ptp61F-RA contains six CDSs, Ptp61F-RB and Ptp61F-RC have seven CDSs, and Ptp61F-RD and Ptp61F-RE have four CDSs. In D. ananassae, the isoform count is not conserved (see Special characteristics of the protein model), and we predict five total isoforms (Ptp61F-PA, Ptp61F-PB, Ptp61F-PD, Ptp61F-PE,and Ptp61F-PNF). The sequence of Ptp61F-PA in Drosophila ananassae has 76.87% identity (E-value: 0.0) with the protein-coding isoform Ptp61F-PA in D. melanogaster, as determined by blastp (Figure 1C). Given that D. ananassae and D. melanogaster belong to distinct species groups, the observed degree protein divergence is well explained and consistent with that seen in other ortholog comparisons between these two species (Drosophila 12 Genomes Consortium et al., 2007). Coordinates of this curated gene model are stored by NCBI at GenBank/BankIt (accessions BK064622, BK064623, BK064624, BK064625, and BK064626). These data are also archived in the CaltechDATA repository (see “Extended Data” section below).
Special characteristics of the protein model
We hypothesize that the isoform Ptp61F-PC does not exist in D. ananassae. In addition, we hypothesize that there is a new isoform, Ptp61F-PNF, due to alternative splicing. Ptp61F-PC in D. melanogaster has a long first intron that has six genes nested within it, but this does not appear in D. ananassae (Figure 1A). A tblastn search of the amino acid sequence of the first CDS in Ptp61F-PC in D. melanogaster against the D. ananassae genome did not return any results, and there are no predicted splice junctions consistent with a long first intron for Ptp61F-PC in this species. This leads us to conclude that the Ptp61F-PC isoform is not present in D. ananassae. Finally, we determined that XM_032453921 (LOC6492936) is a novel isoform, as there is not an orthologous isoform in D. melanogaster that has the same gene structure. It has seven CDSs, and its sixth CDS is longer than the corresponding CDS in isoform Ptp61F-PB (Figure 1D). The seventh CDS of the proposed novel isoform is only eight base pairs long (including the stop codon), as compared to 37 base pairs long for the seventh CDS of isoform Ptp61F-RB. The sixth and seventh CDSs of this novel isoform are supported by a splice junction with a score of 457 (Figure 1D, shown in pink). These features of XM_032453921 (LOC6492936) lead us to believe that new alternative splicing has occurred, resulting in a novel isoform. This novel isoform has 75.86% protein identity (E-value: 0.0) to the D. melanogaster Ptp61F-PB isoform. We propose that this isoform be named Ptp61F-PNF.
","references":[{"reference":"Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. J Mol Biol 215(3): 403-10.
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