Adaptive evolution of proteins secreted during sperm maturation: an analysis of the mouse epididymal transcriptome

Abstract

A common pattern observed in molecular evolution is that reproductive genes tend to evolve rapidly. However, most previous studies documenting this rapid evolution are based on genes expressed in just a few male reproductive organs. In mammals, sperm become motile and capable of fertilization only after leaving the testis, during their transit through the epididymis. Thus, genes expressed in the epididymis are expected to play important roles in male fertility. Here, we performed evolutionary genetic analyses on the epididymal transcriptome of mice. Overall, epididymis-expressed genes showed evidence of strong evolutionary constraint, a finding that contrasts with most previous analyses of genes expressed in other male reproductive organs. However, a subset of epididymis-specialized, secreted genes showed several signatures of adaptive evolution, including an increased rate of nonsynonymous evolution. Furthermore, this subset of genes was overrepresented on the X chromosome. Immunity and protein modification functions were significantly overrepresented among epididymis-specialized, secreted genes. These analyses identified a group of genes likely to be important in male reproductive success.

Fig. 1

An illustration of the epididymis (reprinted with permission from Biology of Reproduction) showing the 10 morphologically defined segments that were interrogated for patterns of gene expression.

Fig. 2

The distribution of the 16,312 genes included in this study with respect to expression definition. Epi-expressed: the number of genes expressed in the epididymis. Epi-selective: the number of genes that were mostly expressed in the epididymis compared with 22 other tissues. Epi-exclusive: the number of genes that were only expressed in the epididymis compared with 22 other tissues. Segmentally regulated: the number of genes that were mostly expressed in one or a few epididymal segments.

Fig. 3

The number of sperm membrane protein genes with transcripts detected in the epididymis and/or testis.

Fig. 4

Median pairwise estimates of d_N/d_S between mouse and rat one-to-one orthologs. Numbers within bars indicate the number of genes. Error bars represent 95% CI around the median, constructed from 10,000 bootstrap replicates.

Fig. 5

Rank order of d_N/d_S among tissue-specialized genes. Tissues were included if at least 20 genes were selectively expressed in them.