Fig 2. Sex chromosomes and DC.

(Top left) Sex chromosomes are highly dynamic and show recurrent turnovers illustrated by gray arrows. They typically evolve from a pair of regular autosomes after acquisition of a sex-determining locus. Recombination starts to be repressed and the future Y (in the case of a male heterogametic species) or W (in the case of a female heterogametic species) acquire more and more protein truncating mutations. This process results in gradual functional heterozygosity of the X or Z chromosome (pink). In some organisms, the sex chromosomes then become fully degenerated and are sometimes even entirely lost, but there are also many species, where sex chromosomes do not decay [37]. Despite degeneration, some genes can be retained [41] or even become expanded on the degenerating Y/W [108]. (Top right) Evolutionary tree showing multiple species across the animal and plant kingdom, where DC has been studied. XY and ZW sex chromosome systems are colored in blue and orange, respectively, and the presence of chromosome-wide versus gene by gene/absence of DC are illustrated with black and gray boxes. Pictograms (images: phylopic.org) are only shown for illustrative purposes and do not depict the actual species in the tree; also see references and comments in S1 File. (Bottom) Comparison of the 3 known molecular mechanisms achieving DC by up-regulation of the X in males (Drosophila), inactivation of the X in females (mammals) or dampening of the 2 X by half in hermaphrodites (nematodes) are compared in the table. In Drosophila, both X-to-autosome as well as male-to-female DC is reached. Mammalian females undergo X chromosome inactivation, where besides selection to correct for dosage imbalance, sexual antagonism has been proposed as an alternative mechanism shaping X inactivation during evolution [109]. Whether the remaining, active X and the single male X are globally up-regulated by 2-fold remains ambiguous to date. While transcriptional mechanisms have been broadly investigated [110–112], a recent study comparing different vertebrates suggests that this second level of compensation according to Ohno’s hypothesis is achieved via translational regulation [113]. DC, dosage compensation.