Sex Chromosome Degeneration by Regulatory Evolution

Abstract

In many species, the Y (or W) sex chromosome is degenerate. Current theory proposes that this degeneration follows the arrest of recombination and results from the accumulation of deleterious mutations due to selective interference-the inefficacy of natural selection on non-recombining genomic regions. This theory requires very few assumptions, but it does not robustly predict fast erosion of the Y (or W) in large populations or the stepwise degeneration of several small non-recombining strata. We propose a new mechanism for Y/W erosion that works over faster timescales, in large populations, and for small non-recombining regions (down to a single sex-linked gene). The mechanism is based on the instability and divergence of cis-regulatory sequences in non-recombining genome regions, which become selectively haploidized to mask deleterious mutations on coding sequences. This haploidization is asymmetric, because cis-regulators on the X cannot be silenced (otherwise there would be no expression in females). This process causes rapid Y/W degeneration and simultaneous evolution of dosage compensation, provided that autosomal trans-regulatory sequences with sex-limited effects are available to compensate for cis-regulatory divergence. Although this "degeneration by regulatory evolution" does not require selective interference, both processes may act in concert to further accelerate Y degeneration.