Figure 1. The X chromosome and autosomes of Drosophila melanogaster differ in retrogene and male-biased gene content. (A) Relative proportions of retrogenes that have moved from the X chromosome to the autosomes (XRA), the autosomes to the X chromosome (ARX), or from one autosome to another (ARA). The dashed line indicates the expected (random) proportion. Data are from [2]. (B) The proportion of X- linked genes (relative to the random expectation; dashed line) for male-biased genes of five categories, including those expressed in whole adult males, testes, somatic male tissues, accessory glands (AG), and sperm. Data are from [3,11,18]. (C) Complementary expression of X-linked parental genes (black) and their autosomal retroposed copies (red) during the mitosis and meiosis stages of spermatogenesis. Data are from [4]. doi:10.1371/journal.pgen.1000724.g001 cases, they found that the new autosomal copies had higher expression at the meiosis stage than at the mitosis stage, while their X-linked parental genes showed the oppo- site pattern (Figure 1C). Such complemen- tary gene expression would be expected if selection favored genes that moved from the X chromosome to the autosomes in order to escape MSCI and increase their expression during the later stages of spermatogenesis. It is likely that this effect of MSCI is relevant not only to Drosophila, but also to other taxa with XY sex determination, as a similar excess of retrogene movement from the X chromosome to the autosomes has been observed in mammals [9,10]. References 1. Vicoso B, Charlesworth B (2006) Evolution on the X chromosome: unusual patterns and processes. Nat Rev Genet 7: 645–653. 2. Betra´n E, Thornton K, Long M (2002) Retro- posed new genes out of the X in Drosophila. Genome Res 12: 1854–1859. 3. 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. 4. Vibranovski MD, Lopes HF, Karr TL, Long M (2002) Stage-specific expression profiling of Dro- sophila spermatogenesis suggests that meiotic sex chromosome inactivation drives genomic reloca- tion of testis expressed genes. PLoS Genet 5(11): e1000731. doi:10.1371/journal.pgen.1000731. 5. Lifschytz E, Lindsley DL (1972) The role of X- chromosome inactivation during spermatogene- sis. Proc Natl Acad Sci U S A 69: 182–186. 6. Namekawa SH, Lee JT (2009) XY and ZW: Is meiotic sex chromosome inactivation the rule in evolution? PLoS Genet 5(5): e1000493. doi:10.1371/journal.pgen.1000493. Can MSCI explain the genomic distri- bution of genes with male-biased expres- sion? Here, the answer is not so clear. The strongest argument against MSCI as a major factor shaping the genomic distribu- tion of male-biased genes in Drosophila is that genes with male-biased expression in somatic tissues also are under-represented on the X chromosome (Figure 1B) [3,7,11]. An alternative hypothesis involving the differential accumulation of sexually antag- onistic mutations (those that are beneficial to one sex but detrimental to the other) on the X chromosome and autosomes may better explain the genomic distribution of male-biased genes [12–14]. However, crit- 7. Sturgill D, Zhang Y, Parisi M, Oliver B (2007) Demasculinization of X chromosomes in the Drosophila genus. Nature 8: 238–224. 8. Hense W, Baines JF, Parsch J (2007) X chromo- some inactivation during Drosophila spermatogen- esis. PLoS Biol 5(10): e273. doi:10.1371/ journal.pbio.0050273. 9. Emerson JJ, Kaessmann H, Betra´n E, Long M (2004) Extensive gene traffic on the mammalian X chromosome. Science 303: 537–540. 10. 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Future studies are needed to determine the relative contributions of MSCI and sexual antago- nism (or other factors) to differences in gene content between the X chromosome and the autosomes. 13. Charlesworth B, Coyne JA, Barton NH (1987) The relative rates of evolution of sex chromo- somes and autosomes. Am Nat 130: 113–146. 14. Ellegren H, Parsch J (2007) The evolution of sex- biased genes and sex-biased gene expression. Nat Rev Genet 8: 689–698. 15. Khil PP, Smirnova NA, Romanienko PJ, Camer- ini-Otero RD (2004) The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation. Nat Genet 36: 642–646. 16. Lercher MJ, Urrutia AO, Hurst LD (2003) Evidence that the human X chromosome is enriched for male-specific but not female-specific genes. Mol Biol Evol 20: 1113–1116. 17. Dean MD, Good JM, Nachman MW (2008) Adaptive evolution of proteins secreted during sperm maturation: an analysis of the mouse epididymal transcriptome. Mol Biol Evol 25: 383–392. 18. Dorus S, Busby SA, Gerike U, Shabanowitz J, Hunt DF, Karr TL (2006) Genomic and functional evolution of the Drosophila melanogaster sperm proteome. Nat Genet 38: 1440–1445. PLoS Genetics | www.plosgenetics.org 2 November 2009 | Volume 5 | Issue 11 | e1000724