A Genetic Basis for a Postmeiotic X Versus Y Chromosome Intragenomic Conflict in the Mouse 英文参考文献.docVIP

AGeneticBasisforaPostmeioticXVersusY ChromosomeIntragenomicConflictintheMouse JulieCocquet1,2,3*,PeterJ.I.Ellis4,ShanthaK.Mahadevaiah5,NabeelA.Affara4,DanielVaiman1,2,3, PaulS.Burgoyne5 1Inserm,U1016,InstitutCochin,Paris,France,2CNRS,UMR8104,Paris,France,3Universite′ParisDescartes,SorbonneParisCite′,Paris,France,4DepartmentofPathology, MammalianMolecularGeneticsGroup,UniversityofCambridge,Cambridge,UnitedKingdom,5DivisionofStemCellBiologyandDevelopmentalGenetics,MRCNational InstituteforMedicalResearch,London,UnitedKingdom Abstract Intragenomicconflictsarisewhenageneticelementfavoursitsowntransmissiontothedetrimentofothers.Conflictsover sexchromosometransmissionareexpectedtohaveinfluencedgenomestructure,generegulation,andspeciation.Inthe mouse,theexistenceofanintragenomicconflictbetweenX-andY-linkedmulticopygeneshaslongbeensuggestedbut never demonstrated. The Y-encoded multicopy gene Sly has been shown to have a predominant role in the epigenetic repression of post meiotic sex chromatin (PMSC) and, as such, represses X and Y genes, among which are its X-linked homologsSlxandSlxl1.Here,weproducedmicethataredeficientforbothSlyandSlx/Slxl1andobservedthatSlx/Slxl1has anoppositeroletothatofSly,inthatitstimulatesXYgeneexpressioninspermatids.Slx/Slxl1deficiencyrescuesthesperm differentiationdefectsandnearsterilitycausedbySlydeficiencyandviceversa.Slx/Slxl1deficiencyalsocausesasexratio distortiontowardstheproductionofmaleoffspringthatiscorrectedbySlydeficiency.Allinall,ourdatashowthatSlx/Slxl1 andSlyhaveantagonisticeffectsduringspermdifferentiationandareinvolvedinapostmeioticintragenomicconflictthat causes segregation distortion and male sterility. This is undoubtedly what drove the massive gene amplification on the mouseXandYchromosomes.ItmayalsobeatthebasisofcasesofF1malehybridsterilitywherethebalancebetweenSlx/ Slxl1 and Sly copy number, and therefore expression, is disrupted. To the best of our knowledge, our work is the first demonstrationofacompetitionoccurringbetwee