PT - JOURNAL ARTICLE AU - Yang, Qiming AU - Lo, Te-Wen AU - Brejc, KatjuĊĦa AU - Schartner, Caitlin AU - Ralston, Edward J. AU - Lapidus, Denise M. AU - Meyer, Barbara J. TI - X-Chromosome Target Specificity Diverged Between Dosage Compensation Mechanisms of Two Closely Related <em>Caenorhabditis</em> Species AID - 10.1101/2022.12.05.519163 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.12.05.519163 4099 - http://biorxiv.org/content/early/2022/12/07/2022.12.05.519163.short 4100 - http://biorxiv.org/content/early/2022/12/07/2022.12.05.519163.full AB - An evolutionary perspective enhances our understanding of biological mechanisms. Comparison of sex determination and X-chromosome dosage compensation mechanisms between the closely related nematode species C. briggsae (Cbr) and C. elegans (Cel) revealed that the genetic regulatory hierarchy controlling these processes is conserved, but both the X-chromosome target specificity and mode of binding for the specialized condensin dosage compensation complex (DCC) controlling X gene expression have diverged. We identified two motifs within Cbr DCC 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 binding in vivo. Hence, DCC binding to Cbr recruitment sites appears additive. In contrast, DCC binding to Cel recruitment sites is synergistic: mutating even one motif in vivo eliminated 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. This functional divergence was demonstrated in vivo and in vitro. A single nucleotide position in Cbr MEX can act as a critical determinant for whether Cel DCC binds. The rapid divergence of DCC target specificity could have contributed to nematode speciation and contrasts dramatically with the conservation of target specificity for transcription factors that control developmental processes such as body-plan specification from fruit flies to mice.Competing Interest StatementThe authors have declared no competing interest.