{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T02:09:10Z","timestamp":1783822150703,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T00:00:00Z","timestamp":1547078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1-AI059342 and R56-AI110721A1"],"award-info":[{"award-number":["RO1-AI059342 and R56-AI110721A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Insects"],"abstract":"<jats:p>Aedes aegypti is an important mosquito vector of several arboviruses, including dengue, yellow fever, Zika, and Chikungunya, which cause significant human morbidity and mortality globally. In certain populations of this mosquito, a native meiotic drive system causes abnormal spermatogenesis that results in highly male-biased progenies from some matings. Although the basic genetics and cytogenetics of the drive mechanism were elucidated, very little is known on a transcriptome level about how the meiotic drive phenotype is expressed in individual males. To address this question, we conducted a whole-genome microarray expression study of testes from a meiotic-drive-carrying strain (T37) in comparison with testes from a non-drive-carrying strain (RED). Based on bioinformatics analyses of the microarray data, we identified 209 genes associated with the meiotic drive phenotype that were significantly differentially expressed between the two strains. K-means cluster analysis revealed nine clusters, in which genes upregulated in T37 testes were assigned to five clusters and genes downregulated in T37 testes were assigned to four clusters. Our data further revealed that genes related to protein translation, phosphorylation, and binding, as well as to G-protein-coupled receptor (GPCR) and peptidase activities, are differentially upregulated in testes from males with the meiotic drive genotype. Based on pathway analysis of these differentially expressed genes, it was observed that the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway may play a role in the meiotic drive system. Overall, this investigation enhances our understanding of whole-genome gene expression associated with the meiotic drive system in Ae. aegypti.<\/jats:p>","DOI":"10.3390\/insects10010025","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T04:10:16Z","timestamp":1547179816000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genome-Wide Transcriptome Profiling Reveals Genes Associated with Meiotic Drive System of Aedes aegypti"],"prefix":"10.3390","volume":"10","author":[{"given":"Dongyoung","family":"Shin","sequence":"first","affiliation":[{"name":"Florida Medical Entomology Laboratory, Department of Entomology and Nematology, University of Florida, Vero Beach, FL 32962, USA"},{"name":"Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanta K.","family":"Behura","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA"},{"name":"Division of Animal Sciences &amp; Informatics Institute, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5798-3365","authenticated-orcid":false,"given":"David W.","family":"Severson","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Severson, D.W., and Behura, S.K. (2016). Genome investigations of vector competence in Aedes aegypti to inform novel arbovirus disease control approaches. Insects, 7.","DOI":"10.3390\/insects7040058"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/s41586-018-0318-5","article-title":"Challenges and opportunities in controlling mosquito-borne infections","volume":"559","author":"Ferguson","year":"2018","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s40475-013-0007-2","article-title":"Novel genetic and molecular tools for the investigation and control of dengue virus transmission by mosquitoes","volume":"1","author":"Franz","year":"2014","journal-title":"Curr. Trop. Med. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Macias, V.M., Ohm, J.R., and Rasgon, J.L. (2017). Gene drive for mosquito control: Where did it come from and where are we headed?. Int. J. Environ. Res. Public Health, 14.","DOI":"10.3390\/ijerph14091006"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1126\/science.132.3443.1887","article-title":"An inherited male-producing factor in Aedes aegypti","volume":"23","author":"Craig","year":"1960","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/genetics\/53.6.1177","article-title":"Distortion of sex ratio in a mosquito Aedes aegypti","volume":"53","author":"Hickey","year":"1966","journal-title":"Genetics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1603\/0022-2585-41.6.1027","article-title":"Reinvestigation of an endogenous meiotic drive system in the mosquito Aedes aegypti (Diptera: Culicidae)","volume":"41","author":"Mori","year":"2004","journal-title":"J. Med. Entomol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4269\/ajtmh.2006.75.70","article-title":"Population dynamics of an endogenous meiotic drive system in Aedes aegypti in Trinidad","volume":"75","author":"Cha","year":"2006","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_9","first-page":"4","article-title":"Sex-linkage in Aedes aegypti","volume":"56","author":"McClelland","year":"1962","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1139\/g66-033","article-title":"Distortion of sex ratio in populations of Aedes aegypti","volume":"8","author":"Hickey","year":"1966","journal-title":"Can. J. Genet. Cytol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/BF00055473","article-title":"A cytogenetic analysis of meiotic drive in the mosquito, Aedes aegypti (L.)","volume":"46","author":"Newton","year":"1976","journal-title":"Genetica"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1017\/S0016672300017195","article-title":"Resistance to meiotic drive at the MD locus in an Indian wild population of Aedes aegypti","volume":"29","author":"Suguna","year":"1977","journal-title":"Genet. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1086\/285171","article-title":"Sex-ratio distortion caused by meiotic drive in mosquitoes","volume":"137","author":"Wood","year":"1991","journal-title":"Am. Nat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF00284986","article-title":"X and Y-chromosomes of Aedes aegypti (L.) distinguished by Giemsa C-banding","volume":"49","author":"Newton","year":"1974","journal-title":"Chromosoma"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1093\/jhered\/esr134","article-title":"Genetic mapping a meiotic driver that causes sex ratio distortion in the mosquito Aedes aegypti","volume":"103","author":"Shin","year":"2012","journal-title":"J. Hered."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/BF00126980","article-title":"The genetic basis of resistance and sensitivity to the meiotic drive gene D in the mosquito Aedes aegypti L.","volume":"72","author":"Wood","year":"1987","journal-title":"Genetica"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.jinsphys.2011.05.014","article-title":"Transcript profiling of the meiotic drive phenotype in testis of Aedes aegypti using suppressive subtractive hybridization","volume":"57","author":"Shin","year":"2011","journal-title":"J. Insect Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Clemons, A., Mori, A., Haugen, M., Severson, D.W., and Duman-Scheel, M. (2010). Culturing and egg collection of Aedes aegypti. Cold Spring Harb. Protoc.","DOI":"10.1101\/pdb.prot5507"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1126\/science.1138878","article-title":"Genome sequence of Aedes aegypti, a major arbovirus vector","volume":"316","author":"Nene","year":"2007","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Behura, S.K., Gomez-Machorro, C., Harker, B.W., deBruyn, B., Lovin, D.D., Hemme, R.R., Mori, A., Romero-Severson, J., and Severson, D.W. (2011). Global cross-talk of genes of the mosquito Aedes aegypti in response to dengue virus infection. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001385"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/biostatistics\/4.2.249","article-title":"Exploration, normalization, and summaries of high density oligonucleotide array probe level data","volume":"4","author":"Irizarry","year":"2003","journal-title":"Biostatistics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"ref_23","first-page":"768","article-title":"Cluster analysis of multivariate data: Efficiency versus interpretability of classifications","volume":"21","author":"Forgy","year":"1965","journal-title":"Biometrics"},{"key":"ref_24","unstructured":"(2011, February 05). VectorBase. Available online: https:\/\/www.vectorbase.org."},{"key":"ref_25","unstructured":"(2018, November 05). Graeber Lab. Available online: http:\/\/systems.crump.ucla.edu\/hypergeometric\/."},{"key":"ref_26","unstructured":"(2011, February 10). KEGG. Available online: http:\/\/www.genome.jp\/kegg-bin\/get_htext?aag00001.keg."},{"key":"ref_27","unstructured":"(2010, January 10). R-Project. Available online: www.r-project.org."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1093\/genetics\/158.3.1125","article-title":"Identification of a polymorphic mucin-like gene expressed in the midgut of the mosquito, Aedes aegypti, using an integrated bulked segregant and differential display analysis","volume":"158","author":"Morlais","year":"2001","journal-title":"Genetics"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Chauhan, C., Behura, S.K., de Bruyn, B., Lovin, D.D., Harker, B.W., Gomez-Machorro, C., Mori, A., Romero-Severson, J., and Severson, D.W. (2012). Comparative expression profiles of midgut genes in dengue virus refractory and susceptible Aedes aegypti across critical period for virus infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047350"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Harker, B.W., Behura, S.K., deBruyn, B., Lovin, D.D., Mori, A., Romero-Severson, J., and Severson, D.W. (2013). Stage-specific transcription during development of Aedes aegypti. BMC Dev. Biol., 13.","DOI":"10.1186\/1471-213X-13-29"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/biot.200700169","article-title":"Statistical methods for efficiency adjusted real-time PCR quantification","volume":"3","author":"Yuan","year":"2008","journal-title":"Biotechnol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u2206\u2206CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_33","unstructured":"(2013, January 16). NCBI-GEO, Available online: https:\/\/www.ncbi.nlm.nih.gov\/geo\/."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/hdy.1997.172","article-title":"Selected lines of Aedes aegypti with persistently distorted sex ratios","volume":"79","author":"Wood","year":"1997","journal-title":"Heredity"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1126\/science.283.5408.1742","article-title":"Truncated RanGAP encoded by the Segregation Distorter locus of Drosophila","volume":"283","author":"Merrill","year":"1999","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1017\/S0016672300031189","article-title":"Meiotic drive on aberrant chromosome 1 in the mouse is determined by a linked distorter","volume":"61","author":"Agulnik","year":"1993","journal-title":"Genet. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S1534-5807(01)00042-9","article-title":"Nuclear mislocalization of enzymatically active RanGAP causes segregation distortion in Drosophila","volume":"1","author":"Kusano","year":"2001","journal-title":"Dev. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1534\/genetics.112.141390","article-title":"The selfish Segregation Distorter gene complex of Drosophila melanogaster","volume":"192","author":"Larracuente","year":"2012","journal-title":"Genetics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1080\/10425170600805540","article-title":"Isolation and characterization of the RanGAP gene in the mosquito Aedes aegypti","volume":"17","author":"Cha","year":"2006","journal-title":"DNA Seq."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/ng1617","article-title":"The t complex-encoded GTPase activating protein Tagap1 acts as a transmission ratio distorter in mice","volume":"37","author":"Bauer","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4269\/ajtmh.2006.74.62","article-title":"Cage trials using an endogenous meiotic drive gene in the mosquito, Aedes aegypti, to promote population replacement","volume":"74","author":"Cha","year":"2006","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.ibmb.2007.06.002","article-title":"Introducing transgenes into insect populations using combined gene-drive strategies: Modeling and analysis","volume":"37","author":"Huang","year":"2007","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.devcel.2004.05.011","article-title":"GPI-anchor synthesis: Ras takes charge","volume":"6","author":"Hancock","year":"2004","journal-title":"Dev. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.molcel.2012.05.007","article-title":"Cooperative activation of PI3K by Ras and Rho family small GTPases","volume":"47","author":"Yang","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.cell.2013.04.031","article-title":"RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms","volume":"153","author":"Fritsch","year":"2013","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0968-0004(03)00087-2","article-title":"Does Rap1 deserve a bad Rap?","volume":"28","author":"Stork","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1089\/ars.2010.3401","article-title":"Reative oxygen species-dependent cell signaling regulates the mosquito immune response to Plasmodium falciparum","volume":"14","author":"Surachetpong","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1128\/IAI.00024-12","article-title":"Ingested human insulin inhibits the mosquito NF-kB-dependent response to Plasmodium falciparum","volume":"80","author":"Pakpour","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ibmb.2010.10.001","article-title":"The small GTPase Rheb is a key component linking amino acid signaling and TOR in the nutritional pathway that controls mosquito egg development","volume":"41","author":"Roy","year":"2011","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1096\/fj.11-189969","article-title":"Nutritional and hormonal regulation of the TOR effector 4E-binding protein (4E-BP) in the mosquito Aedes aegypti","volume":"26","author":"Roy","year":"2012","journal-title":"FASEB J."}],"container-title":["Insects"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4450\/10\/1\/25\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:24:50Z","timestamp":1760185490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4450\/10\/1\/25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,10]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["insects10010025"],"URL":"https:\/\/doi.org\/10.3390\/insects10010025","relation":{},"ISSN":["2075-4450"],"issn-type":[{"value":"2075-4450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,10]]}}}