X-Chromosome Target Specificity Diverged Between Dosage Compensation Mechanisms of Two Closely RelatedCaenorhabditisSpecies

Abstract

AbstractAn evolutionary perspective enhances our understanding of biological mechanisms. Comparison of sex determination and X-chromosome dosage compensation mechanisms between the closely related nematode speciesC. briggsae(Cbr) andC. elegans(Cel) revealed that the genetic regulatory hierarchy controlling both processes is conserved, but the X-chromosome target specificity and mode of binding for the specialized condensin dosage compensation complex (DCC) controlling X expression have diverged. We identified two motifs withinCbrDCC recruitment sites that are highly enriched on X: 13-bp MEX and 30-bp MEX II. Mutating either MEX or MEX II in an endogenous recruitment site with multiple copies of one or both motifs reduced binding, but only removing all motifs eliminated bindingin vivo. Hence, DCC binding toCbrrecruitment sites appears additive. In contrast, DCC binding toCelrecruitment sites is synergistic: mutating even one motifin vivoeliminated binding. Although all X-chromosome motifs share the sequence CAGGG, they have otherwise diverged so that a motif from one species cannot function in the other. Functional divergence was demonstratedin vivoandin vitro. A single nucleotide position inCbrMEX can determine whetherCelDCC binds. This rapid divergence of DCC target specificity could have been an important factor in establishing reproductive isolation between nematode species and contrasts dramatically with conservation of target specificity for X-chromosome dosage compensation acrossDrosophilaspecies and for transcription factors controlling developmental processes such as body-plan specification from fruit flies to mice.