What makes the Y chromosome, with its confounding repeats, polymorphisms, and degenerating regions, such an interesting study object for male infertility?

The answer lies in the evolutionary history of the X and Y chromosomes. Over the course of the past 240-320 million years of mammalian evolution, the X and Y chromosomes have evolved from what was originally a pair of ordinary autosomes (Figure 5). During that evolution, just as most of the ancestral X genes were decaying on the Y because of the lack of meiotic recombination, genes which control spermatogenesis arrived on the Y from autosomes. Once on the Y, these formerly autosomal genes amplified into multiple copies, and achieved greater prominence through a process called “gene conversion.” Spermatogenesis genes that arrived on the Y, but came originally from autosomes, include the DAZ (from autosome 3) and CDY (from autosome 6) genes that are among the seven gene families located in AZFc (Figure 6). Other spermatogenesis genes on the Y, such as RBMY, have persisted in their original position as on the X. The ancestral gene that remained on the X chromosome (RBMX) retained its widespread cellular functions, whereas RBMY, which persisted on the receding Y chromosome, evolved a male-specific function in spermatogenesis. Male benefit genes have thus arrived and accumulated on the evolving Y chromosome over many millions of years.

This evolution of the modern X and Y chromosomes was initiated by the emergence of a male sex-determining gene (now known as SRY) on what was originally an ordinary pair of autosomes (Figure 5). Genes associated with the non-recombining SRY region that were specifically beneficial for male function or antagonistic to female function, flourished on the evolving Y chromosome despite the deterioration of more generalized genes which lacked the DNA repair benefits of meiosis.