PT - JOURNAL ARTICLE AU - Lenormand, Thomas AU - Roze, Denis TI - A single theory for the evolution of sex chromosomes and the two rules of speciation AID - 10.1101/2024.03.18.585601 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.03.18.585601 4099 - http://biorxiv.org/content/early/2024/11/20/2024.03.18.585601.short 4100 - http://biorxiv.org/content/early/2024/11/20/2024.03.18.585601.full AB - Three major empirical patterns involving sex chromosomes have been observed in higher eukaryotes: Y (or W) chromosomes are often non-recombining and degenerate; when two species hybridize, but one sex is sterile or inviable among hybrid offspring, it is most often the heterogametic sex (XY or ZW)—the so-called Haldane’s rule; and the X (or Z) plays a disproportionately large effect on reproductive isolation compared to autosomes—the so-called large X effect. Each observation has generally received its own tailored explanation involving multiple genetic and evolutionary causes1–3. Here, we show that these empirical patterns all emerge from a single theory for sex chromosome evolution incorporating the co-evolution of cis and trans-acting regulators of gene expression, and leading to systematic and rapid misexpression of dosage-compensated genes in the heterogametic F1 hybrids, for young or old sex-chromosomes. This theory links the evolution of sex chromosomes to the patterns of post-zygotic isolation observed in hybrids.Competing Interest StatementThe authors have declared no competing interest.