I previously described where in a genome we would expect to find sexually antagonistic genes. Briefly, depending on whether a gene is male-biased or female-biased and whether beneficial mutations are dominant or recessive, we can predict whether these sexually antagonistic genes will be on X chromosomes or autosomes. As I mentioned in that post, the theoretical results can only be translated into realistic predictions if we have reliable estimates of the relevant parameters. We do not have such estimates, but we can study the distribution of sex-biased genes throughout genomes. The results of such experiments can then be used to infer how selection acts upon sexually antagonistic genes.

With the publication of complete genome sequences from multiple different animals, gene content on X chromosomes on autosomes could be compared. Manyuan Long’s research group performed some of these early studies, including one where they looked at duplicated genes in the Drosophila melanogaster genome [Retroposed New Genes Out of the X in Drosophila]. The found an excess of duplicated genes with an ancestral copy on the X chromosome and a derived copy on an autosome. When they examined the expression patterns of these genes, they found that many of the autosomal copies of genes duplicated from the X chromosome were transcribed in the testes. It appeared that male-biased genes were accumulating on the autosomes and selected against on the X chromosome.

However, to explain the pattern, Long and colleagues did not invoke sexual antagonism. Instead, they pointed out that the X chromosome is inactivated during spermatogenesis. Therefore, testes expressed genes will be selected against if they are located on the X chromosome because they won’t be transcribed during some stages of spermatogenesis. But not everyone agreed with them. Chung-I Wu and Eugene Xu argued that selection against male-biased genes may have driven the testes expressed genes off the X, which then allowed for the evolution of X inactivation [Sexual antagonism and X inactivation -- the SAXI hypothesis].

We’ll get back to the conflict between X inactivation and sexual antagonism in a little bit. But first we’ll take a look at where the male genes are in other organisms. Manyuan Long’s lab also looked at duplicated genes in the human and mouse genomes [Extensive Gene Traffic on the Mammalian X Chromosome]. Just like in Drosophila, they found lots of genes duplicated from the X chromosome to the autosomes, and the autosomal copies were expressed in the testes. But they also found an excess of genes duplicated onto the X chromosome. One model of sexual antagonism predicts that the X-linked copies will be female-biased. Long and colleagues did not find an excess of ovary expressed genes on the X chromosome, so it was unclear why an excess of genes were duplicated onto the X chromosome.

What happens when we explicitly look for male-specific genes? David Page and colleagues did that with mouse transcripts, and they found that genes expressed only in spermatogenesis tend to be found on the X chromosome [An abundance of X-linked genes expressed in spermatogonia]. While the studies on duplicated genes found that male genes accumulate on autosomes, this study discovered that the X chromosome is a disproportionate source of male genes . . . in mice.

But the same pattern does not hold in Drosophila. Brian Oliver’s group compared gene expression in male and female flies and found an underrepresentation of male-biased genes on the X chromosome [Paucity of Genes on the Drosophila X Chromosome Showing Male-Biased Expression]. This is consistent with the studies of duplicated genes. There are two different explanations for this pattern: either sexual antagonism drives male-biased genes off the X chromosome or X inactivation during spermatogenesis prevents testis-expressed genes from accumulating on the X chromosome.

Oliver and colleagues came up with a clever way to compare those hypotheses [Demasculinization of X chromosomes in the Drosophila genus]. They collected gene expression data from males and females of six additional Drosophila species — which was possible thanks to the sequencing of the genomes of those species. Just like in D. melanogaster, all species showed a paucity of X-linked male-biased genes. That can be seen in the first panel of the figure below.

a, Percentage of genes with female-biased (red), non-biased (grey) and male-biased (blue) expression on chromosome arms. Muller’s elements and arms are indicated (X chromosomes in bold). Significant under-representation from a random distribution of genes in an expression class (chi-squared test) is noted (*P < 10-4). The top 20% of differentially expressed genes (by ranked P values) are assigned a sex-biased expression class. b, Box plots of average hybridization intensities for males by chromosome arm. Twenty-fifth to seventy fifth percentiles (boxes), medians (lines in boxes) and ranges (whiskers) are indicated. c, As in a, but with genes with predicted testis-biased expression removed. D. melanogaster, D. mel; D. simulans, D. sim, D. yakuba, D. yak; D. ananassae, D. ana; D. pseudoobscura, D. pse; D. virilis, D. vir; D. mojavensis, D. moj.
[Click to enlarge.]

They then did something clever with the data; they excluded the testis-biased genes (that is genes expressed in testes significantly more than somatic tissue). If X-inactivation drove the male-biased genes off the X chromosome, excluding testis-biased genes should eliminate the discrepancy between the X chromosome and autosomes. If, however, selection against male-biased genes on the X chromosome drives the demasculinization of the X chromosome, removing testis-biased genes from the dataset should have no effect on the discrepancy. It turns out that removing the testis-biased genes does not eliminate the deficiency of male-biased genes on the X chromosome. Oliver and colleagues conclude that natural selection drives male-biased genes off the X chromosome independently of the effects of X inactivation during spermatogenesis.

What are we left with? Well, there is evidence that male-biased genes are selected against on the X chromosome. This supports the hypothesis that beneficial mutations in male-biased genes are dominant. However, this does not hold across all taxa — see the mouse study where testis-specific genes were found on the X chromosome. Could it be that we can’t generalize the dominance of beneficial mutations for different classes of genes (perhaps the testis specific genes have recessive beneficial mutations)? Or maybe the dominance of beneficial mutations varies across taxa.

Betran E, Thornton K, Long M. 2002. Retroposed New Genes Out of the X in Drosophila. Genome Res 12: 1854-1859 doi:10.1101/gr.6049

Emerson JJ, Kaessmann H, Betran E, Long M. 2004. Extensive Gene Traffic on the Mammalian X Chromosome. Science 303: 537-540 doi:10.1126/science.1090042

Parisi M, Nuttall R, Naiman D, Bouffard G, Malley J, et al. 2003. Paucity of Genes on the Drosophila X Chromosome Showing Male-Biased Expression. Science 299: 697-700. doi:10.1126/science.1079190

Sturgill D, Zhang Y, Parisi M, Oliver B. 2007. Demasculinization of X chromosomes in the Drosophila genus. Nature 450: 238-241 doi:10.1038/nature06330

Wang PJ, McCarrey JR, Yang F, Page DC. 2001.An abundance of X-linked genes expressed in spermatogonia. Nat Genet 27: 422-426 doi:10.1038/86927

Wu C-I, Xu EY. 2003. Sexual antagonism and X inactivation — the SAXI hypothesis. Trends Genet 19: 243-247 doi:10.1016/S0168-9525(03)00058-1