An X-to-autosome-to-Y chromosome amplified retrogene family functions in spermatids

Mammalian Y chromosomes acquire lineage-specific gene families^1,2,3,4,5 with spermatogenic functions in male fertility,^1,2,6,7,8 a mechanism that counters Y chromosome decay. However, in most mammals, the mechanisms by which Y chromosomes acquire new gene families and the benefits they confer to males remain poorly understood. Here, we discover that deer mice (Peromyscus) acquired a lineage-specific, massively amplified Y-linked gene family, Phf8y. Phf8y arose via the transposition of autosomal Phf8l, which previously arose via retrotransposition from an X-linked gene, PHD-finger protein 8 (Phf8). Phf8y, Phf8l, and Phf8 are expressed in haploid spermatids, where their encoded proteins each bind FAM178B in Mus musculus and Peromyscus maniculatus, while PHF8 binds ZFP711 in both species, suggesting that PHF8L/PHF8Y have similar functions. By contrast, Mus musculus PHF8L and P. maniculatus PHF8 and PHF8Y bind ZFP318, distinct from PHF8 interactors. We deleted Phf8l in M. musculus and found that neither the loss of Phf8l alone nor the loss of Phf8l and Phf8 together resulted in overt spermatogenesis defects or male infertility. However, Phf8l preferentially represses X-linked genes, and Phf8l and Phf8 cooperatively repress long interspersed element 1 (LINE1) retrotransposons and 5S rRNA. The specific regulation of X-linked genes by Phf8l suggests that while Phf8l does not influence X-bearing versus Y-bearing sperm fitness in M. musculus, acquisition of Phf8y on the Peromyscus Y chromosome may influence sperm fitness. Peromyscus Phf8y resembles the Y-linked Ssty gene family in M. musculus, which is in an evolutionary arms race, suggesting acquired Y-amplified, spermatid-specific gene families are genetic signatures of sex chromosome evolutionary arms races.