Chromosomal gene movements reflect the recent origin and biology of therian sex chromosomes

Abstract

Mammalian sex chromosomes stem from ancestral autosomes and have substantially differentiated. It was shown that X-linked genes have generated duplicate intronless gene copies (retrogenes) on autosomes due to this differentiation. However, the precise driving forces for this out-of-X gene "movement" and its evolutionary onset are not known. Based on expression analyses of male germ-cell populations, we here substantiate and extend the hypothesis that autosomal retrogenes functionally compensate for the silencing of their X-linked housekeeping parental genes during, but also after, male meiotic sex chromosome inactivation (MSCI). Thus, sexually antagonistic forces have not played a major role for the selective fixation of X-derived gene copies in mammals. Our dating analyses reveal that although retrogenes were produced ever since the common mammalian ancestor, selectively driven retrogene export from the X only started later, on the placental mammal (eutherian) and marsupial (metatherian) lineages, respectively. Together, these observations suggest that chromosome-wide MSCI emerged close to the eutherian-marsupial split approximately 180 million years ago. Given that MSCI probably reflects the spread of the recombination barrier between the X and Y, crucial for their differentiation, our data imply that these chromosomes became more widely differentiated only late in the therian ancestor, well after the divergence of the monotreme lineage. Thus, our study also provides strong independent support for the recent notion that our sex chromosomes emerged, not in the common ancestor of all mammals, but rather in the therian ancestor, and therefore are much younger than previously thought.

Figure 1. Expression Pattern of Mouse Parental Genes and Retrogenes in Somatic and Germline Tissues (A), and during Spermatogenesis (B)

Log2 expression signals are represented according to the plotted scale. The two heat maps show signal values for both parental genes (left side) and their respective retrogenes (right side), or only for one of the two, when data are not available for the other. Upper and lower parts of the panels contain pairs with parental genes located on the X chromosome and the autosomes, respectively. Line numbers in the middle of the heat maps correspond to mouse retrogene identifiers in Tables S2 and S5.

Figure 2. Age of Retrogenes

Branches are labeled A to H. “X” refers to the number of X-linked parental genes (in the X conserved region) that produced autosomal retrogenes. “A” refers to the number of autosomal parental genes that generated an autosomal retrogene. The numbers of parental genes producing retrogenes on the lineage leading to humans are indicated by blue arrows; those generating retrogenes on the other lineages are indicated by red arrows. Null expectations for the out-of-X movement (based on the number of genes on the X) are in parentheses, and the significances of resampling tests for observed excesses are indicated (an asterisk [*] indicates p < 0.01). The set of opossum-specific retrogenes is separated into two subsets based on d _S smaller or larger than 0.5, which corresponds to the age of the split of the human–dog lineage (see Materials and Methods). The right side of the figure indicates current knowledge of XCI (female somatic X chromosome inactivation) and MSCI for the major lineages in the tree (see main text for references).