Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes

TLDR: An empirical reconstruction of human MSY evolution is presented, in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.

Abstract: This evolutionary decay was driven by a series of five ‘stratification’ events. Each event suppressed X–Y crossing over within a chromosome segment or ‘stratum’, incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over 2,6 . The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome 7–10 , remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1–4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection. The human Y chromosome no longer engages in crossing over with its once-identical partner, the X chromosome, except in its pseudoautosomal regions. During evolution, X–Y crossing over was suppressed in five different chromosomal regions at five different times, each probably resulting from an inversion in the Y chromosome 2,3 . Each of these regions of the Y chromosome then began its own individual course of degeneration, experiencing deletions and gene loss. Comparison of the present-day X and Y chromosomes enables identification of these five evolutionary ‘strata’ in the MSY (and X chromosome); their distinctive degrees of X–Y differentiation indicate their evolutionary ages 2,3 . The oldest stratum (stratum 1) dates back over 240 million years (Myr) 2 and is the most highly differentiated, and the youngest stratum (stratum 5) originated only 30 Myr ago and displays the highest X–Y nucleotide sequence similarity within the MSY 3 . The five strata and their respective decay processes, over tens to hundreds of millions of years of mammalian evolution, offer replicate experiments of nature from which to reconstruct the trajectories and kinetics of gene loss in the MSY. Only the human and chimpanzee MSYs had been sequenced before the present study, and they are separated by just 6 Myr of evolution. We decided to examine the MSY of a much more distant relative, the rhesus macaque (Macaca mulatta), to enable us to reconstruct gene loss and conservation in the MSY during the past 25 Myr. We sequenced the rhesus MSY using bacterial artificial chromosome (BAC) clones and the SHIMS (single-haplotype iterative mapping and sequencing) strategy that has previously been used in the human and chimpanzee MSYs 4,11–13 as well as in the chicken Z chromosome 5 . The resulting sequence is comprised of 11.0 megabases (Mb), is complete aside from three small gaps and has an error rate of about one nucleotide per Mb. We ordered and oriented the finished sequence contigs by fluorescence in situ hybridization and radiation hybrid mapping (Supplementary Figs 1–6, Supplementary Table 1, Supplemen