Origins of New Male Germ-line Functions from X-Derived Autosomal Retrogenes in the Mouse

Recent literature demonstrates that retrogenes tend to leave the X chromosome and integrate onto the autosomes and evolve male-biased expression patterns. Several selection-based evolutionary mechanisms have been proposed to explain this observation. Testing these selection-based models requires examining the evolutionary history and functional properties of new retrogenes, particularly those that show evidence of directional movement between the X and the autosomes (X-related retrogenes). This includes autosomal retrogenes with parental paralogs on the X chromosome (X-derived autosomal retrogenes) and those retrogenes integrated onto the X chromosomes (X-linked retrogenes). In order to understand why retrogenes tend to move nonrandomly in genomes, we examined the expression patterns and evolutionary mechanisms concerning gene pairs having young retrogenes-originating less than 20 MYA (after mouse-rat split). We demonstrate that these X-derived autosomal retrogenes evolved a more restricted male-biased expression pattern: they are expressed exclusively or predominantly in the testis, in particular, during the late stages of spermatogenesis. In contrast, the parental counterparts have relatively broad expression patterns in various tissues and spermatogenetic stages. We further observed that positive selection is targeting these X-derived autosomal retrogenes with novel male-biased expression patterns. This suggests that such retrogenes evolved new male germ-line functions that may be complementary to the functions of the parental paralogs, which themselves contribute little during spermatogenesis. Such evolutionary changes may be beneficial to the populations. Furthermore, most identified X-related retrogenes have recruited novel adjacent sequences as their untranslated regions (UTRs), suggesting that these UTRs, acquired de novo, may play an important role in establishing new regulatory mechanisms to carry out the new male germ-line functions.