The Cause-Effect Model of Master Sex Determination Gene Acquisition and Evolution of Sex Chromosomes

The canonical model of vertebrate sex chromosome evolution predicts one way of trend toward degradation. However, most sex chromosomes in lower vertebrates are homomorphic. Recent progress in studies of sex determination resulted in the discovery of more than 30 master sex determination (MSD) genes, most of which were from teleost fish. Analysis of MSD gene acquisition, recombination suppression, and sex chromosome-specific sequences revealed correlation of the modes of MSD gene acquisition and evolution of sex chromosomes: Sex chromosomes remain homomorphic with MSD genes acquired by simple mutations, gene duplications, allelic variations or neofunctionalization; in contrast, they become heteromorphic with MSD genes acquired by chromosomal inversions, fusions and fissions. There is no recombination suppression with sex chromosomes carrying MSD genes gained through simple mutations. In contrast, there is extensive recombination suppression with sex chromosomes carrying MSD genes gained through chromosome inversion. There is limited recombination suppression with sex chromosomes carrying MSD genes gained through transpositions or translocations. We proposed the cause-effect model that predicts sex chromosomes evolution being consequential of the acquisition modes of MSD genes, which explains evolution of sex chromosomes in various vertebrates. A key factor determining the trend of sex chromosome evolution is if non-homologous regions are created during the acquisition of MSD genes. Chromosome inversion creates inversely homologous but directly non-homologous sequences which lead to recombination suppression but remain recombination potential. Over time, recurrent recombination in the inverted regions causes degradation of sex chromosomes. Depending on the nature of deletions in the inverted regions, sex chromosomes may evolve with dosage compensation or mechanisms to retain haploinsufficient genes.