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

Abstract

The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay. 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. 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, 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.

Figure 1

Comparison of rhesus, human and chimpanzee Y chromosomes. (a) Schematic representations, to scale. “Other” denotes single-copy, male-specific sequences that are neither X-degenerate nor X-transposed. (b) Sizes (in Mb) of euchromatic sequence classes in MSYs.

Figure 2

Inventories of genes, both ancestral and added, in rhesus, human, and chimpanzee MSYs. At top, ancestral genes grouped by stratum, 1 through 5; added genes listed below. In rhesus, human and chimpanzee, current status of each MSY gene is indicated by shading in one of three columns: i. present and intact, ii. inactivated pseudogene or iii. absent/deleted. Total numbers of MSY-intact genes, pseudogenes, and absent/deleted genes – both ancestral and added – are tallied for each species. At far right is indicated, for each MSY gene, whether the most closely related human homolog is located on the X chromosome.

Figure 3

Kinetics of ancestral gene loss during evolution of five human MSY strata. Gene numbers are plotted on a log scale on the Y axis, and time (in millions of years before present) is plotted on the X axis. Filled circles represent inferred or observed gene numbers in (from left to right): i. X-Y ancestral chromosome (at time of stratum formation), ii. rhesus-chimpanzee-human ancestral MSY (25 mya), iii. chimpanzee-human ancestral MSY (6 mya), and iv. modern human MSY. Dotted/dashed lines represent best-fit curves to data points using each of three decay models as indicated.