Department of Biology, McMaster University, Hamilton, Ontario, Canada
Correspondence: E-mail: torgerdg{at}mcmaster.ca.
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key Words: Faster X evolution human-mouse orthologous genes sperm proteins selection X chromosome
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In the first scenario, there are greater selective constraints on X-linked genes compared with autosomal genes, as any recessive deleterious mutations will be expressed in males and may be subject to stronger purifying selection. Two studies in mammals support this theory and have found X-linked genes to have a significantly lower nonsynonymous substitution rate (Wolfe and Sharp 1993; McVean and Hurst 1997). However, the latter study suggests nonsynonymous substitution rates may in fact be higher than expected on the X chromosome after controlling for a reduced mutation rate (McVean and Hurst 1997).
Alternatively, there are certain conditions where genes on the X chromosome can evolve faster than those on autosomes. If the majority of new mutations are beneficial and are at least partially recessive, haploid expression in the heterogametic sex will result in higher rates of sequence divergence (Charlesworth, Coyne, and Barton 1987). Two studies support the second scenario of faster X evolution due to an increased likelihood of positive selection or a selective sweep of beneficial recessive mutations on the X chromosome. First, reduced polymorphism on the X chromosome has been reported in Drosophila simulans, suggesting that a form of positive selection may be acting on sex chromosomes (Begun and Whitley 2000). Second, gene duplications on the X chromosome in D. melanogaster are highly diverged due to relaxed selective constraint and likely positive selection acting on duplicate copies (Thornton and Long 2002). However, Betancourt, Presgraves, and Swanson (2002) found no evidence for faster X evolution in male-specific genes in Drosophila, but this has not been tested in mammals.
There is little evidence in mammals to suggest a higher divergence of X-linked genes in general; however, there have been no attempts to identify candidate X-linked genes that may be under rapid evolution due to selection on beneficial alleles. The faster evolution of the X chromosome is expected to be enhanced for genes with male-specific expression, as they are always haploid expressed, allowing advantageous recessive mutations to be selected for. The majority of deleterious mutations are thought to be recessive (Crow and Temin 1964; Mukai et al. 1972); however, for male-specific haploid expressed genes, it is not known whether most mutations are deleterious. Previous reports show that many mammalian sperm proteins are evolving rapidly under positive selection (Torgerson, Kulathinal, and Singh 2002; Swanson, Nielsen, and Yang 2003), suggesting that mutations in these genes may often be nondeleterious or even beneficial to rapidly adapting sperm proteins. Moreover, there is a disproportionately high number of sperm proteins found on the mammalian X chromosome (Wang et al. 2001), which may suggest adaptive advantages for sperm proteins to be located on the X chromosome. With the combined evidence of positive selection acting on many sperm proteins and a higher abundance of mammalian sperm proteins on the X chromosome, we hypothesized that sperm proteins on the X chromosome are evolving faster than sperm proteins on the autosomes due to selection acting on beneficial alleles. We provide evidence here that sperm proteins are significantly more diverged on the mammalian X chromosome than sperm proteins located on the autosomes and discuss why this might be so.
![]() |
Materials and Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The expected numbers of substitutions per site at synonymous sites (Ks) and at nonsynonymous sites (Ka) were calculated using Li's method (1993). Estimates of Ka and Ks for other tissue-specific human/mouse orthologs were kindly provided by Laurent Duret at the Université Claude Bernard, France (http://pbil.univ-Lyon1.fr/datasets/Duret_Mouchiroud_1999/data.html), which were also calculated using the method of Li (1993). Only genes expressed exclusively in a single adult tissue were selected for analysis, and any genes expressed in the sperm were excluded. Using a random sample, recalculated divergence estimates were equal to estimates of Ka and Ks from the original data set. Chromosomal location was retrieved from UniGene at NCBI (http://www.ncbi.nlm.nih.gov/UniGene/). An analysis of variance was used to compare the estimates of Ka, Ks, and Ka/Ks between tissue-specific genes on the X chromosome versus autosomes, as well as to compare values of Ks among autosomes.
![]() |
Results and Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
Rapid evolution, including positive selection, has been reported to act on genes involved in the immune response (Hughes, Ota, and Nei 1990; Zhang and Nei 2000) and is particularly widespread in genes involved in sex and reproduction (Singh and Kulathinal 2000; Swanson and Vacquier 2002). To determine why sperm proteins on the X chromosome are evolving faster than sperm proteins on autosomes, a look at the functions of X-linked sperm proteins may give more insight. First, meiotic drive or sexually antagonistic genes may be preferentially located on the X chromosome and may explain why there is a high abundance of sperm proteins on the X chromosome (discussed in Wang et al. 2001). If either meiotic drive or sexually antagonistic genes are evolving rapidly, it may explain a higher rate of amino acid substitution on the X chromosome for these sperm-expressed proteins. Alternatively, rapidly evolving sperm proteins not restricted to meiotic drive or sexually antagonistic genes may have adaptive advantages to being located on the X chromosome to allow for more rapid changes in amino acid composition. Our previous findings show sperm proteins of diverse functional classes are rapidly evolving (Torgerson, Kulathinal, and Singh 2002); therefore, highly diverged sperm proteins on the X chromosome may not be limited to sexually antagonistic or meiotic drive genes.
The functions of X-linked sperm proteins are variable (table 2); however, their past or current involvement in sexual antagonism or in meiotic drive is for the most part unknown. Two of these genes, cylicin I and actin-related protein T1, may be important in sperm head structure, which may affect a sperm's ability to fertilize the egg. The contribution of sperm-egg coevolution in driving the rapid evolution of male traits has been shown previously (see Swanson and Vacquier 2002); however, we find the majority of genes that are involved in direct sperm-egg interactions to be autosomal. It is therefore becoming more apparent that diverse and complex forces of natural and sexual selection are influencing the rapid evolution of male-expressed genes, including chromosomal location.
|
![]() |
Acknowledgements |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Footnotes |
---|
![]() |
Literature Cited |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Baker, R. T., J. W. Tobias, and A. Varshavsky. 1992. Ubiquitin-specific proteases of Saccharomyces cerevisiae: cloning of UBP2 and UBP3, and functional analysis of the UBP gene family. J. Biol. Chem. 267:23364-23375.
Bauer, V. L., and C. F. Aquadro. 1997. Rates of DNA sequence evolution are not sex-biased in Drosophila melanogaster and D. simulans. Mol. Biol. Evol. 14:1252-1257.[Abstract]
Begun, D. J., and P. Whitley. 2000. Reduced X-linked nucleotide polymorphism in Drosophila simulans. Proc. Natl. Acad. Sci. USA 97:5960-5965.
Betancourt, A. J., D. C. Presgraves, and W. J. Swanson. 2002. A test for faster X evolution in Drosophila. Mol. Biol. Evol. 19:1816-1819.
Charlesworth, B., J. A. Coyne, and N. Barton. 1987. The relative rates of evolution of sex chromosomes and autosomes. Am. Nat. 140:126-148.[CrossRef]
Chiang, C. M., and R. G. Roeder. 1995. Cloning of an intrinsic human TFIID subunit that interacts with multiple transcriptional activators. Science 267:531-536.[ISI][Medline]
Civetta, A., and R. S. Singh. 1999. Broad-sense sexual selection, sex gene pool evolution, and speciation. Genome 42:1033-1041.[CrossRef][ISI][Medline]
Crow, J. F., and R. G. Temin. 1964. Evidence for the partial dominance of recessive lethal genes in natural populations of Drosophila. Am. Nat. 98:21-33.[CrossRef][ISI]
de La Casa-Esperon, E., J. C. Loredo-Osti, F. Pardo-Manuel de Villena, T. L. Briscoe, J. M. Malette, J. E. Vaughan, K. Morgan, and C. Sapienza. 2002. X chromosome effect on maternal recombination and meiotic drive in the mouse. Genetics 161:1651-1659.
Gibson, J. R., A. K. Chippindale, and W. R. Rice. 2002. The X chromosome is a hot spot for sexually antagonistic fitness variation. Proc. R. Soc. Lond. B Biol. Sci. 269:499-505.[CrossRef][ISI][Medline]
Gruter, P., C. Tabernero, C. von Kobbe, C. Schmitt, C. Saavedra, A. Bachi, M. Wilm, B. K. Felber, and E. Izaurralde. 1998. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol. Cell 1:649-569.[ISI][Medline]
Heid, H. W., U. Figge, S. Winter, C. Kuhn, R. Zimbelmann, and W. W. Franke. 2002. Novel actin-related proteins Arp-T1 and Arp-T2 as components of the cytoskeletal calyx of the mammalian sperm head. Exp. Cell Res. 279:177-187.[CrossRef][ISI][Medline]
Herold, A., M. Suyama, J. P. Rodrigues, I. C. Braun, U. Kutay, M. Carmo-Fonseca, P. Bork, and E. Izaurralde. 2000. TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved molecular architecture. Mol. Cell. Biol. 20:8996-9008.
Hess, H., H. Heid, R. Zimbelmann, and W. W. Franke. 1995. The protein complexity of the cytoskeleton of bovine and human sperm heads: the identification and characterization of cylicin II. Exp. Cell Res. 218:174-182.[CrossRef][ISI][Medline]
Hughes, A. L., T. Ota, and M. Nei. 1990. Positive Darwinian selection promotes charge profile diversity in the antigen-binding cleft of class I major-histocompatibility-complex molecules. Mol. Biol. Evol. 7:515-524.[Abstract]
Kang, Y., and B. R. Cullen. 1999. The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences. Genes Dev. 13:1126-1139.
Lawson, D. M., P. J. Artymiuk, and S. J. Yewdall, et al. (13 co-authors). 1991. Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. Nature 349:541-544.[CrossRef][ISI][Medline]
Lercher, M. J., E. J. B. Williams, and L. D. Hurst. 2001. Local similarity in evolutionary rates extends over whole chromosomes in human-rodent and mouse-rat comparisons: implications for understanding the mechanistic basis of the male mutation bias. Mol. Biol. Evol. 18:2032-2039.
Li, W. 1993. Unbiased estimation of the rates of synonymous and nonsynonymous substitution. J. Mol. Evol. 26:96-99.
McVean, G. T., and L. D. Hurst. 1997. Evidence for a selectively favourable reduction in the mutation rate of the X chromosome. Nature 386:388-392.[CrossRef][ISI][Medline]
Mukai, T., S. I. Chigusa, L. E. Mettler, and J. F. Crow. 1972. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics 72:335-355.
Nagai, K. 2001. Molecular evolution of Sry and Sox gene. Gene 270:161-169.[CrossRef][ISI][Medline]
Pask, A., and J. A. Graves. 1999. Sex chromosomes and sex-determining genes: insights from marsupials and monotremes. Cell Mol. Life Sci. 55:864-875.[CrossRef][ISI][Medline]
Segref, A., K. Sharma, V. Doye, A. Hellwig, J. Huber, R. Luhrmann, and E. Hurt. 1997. Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores. Embo. J. 16:3256-3271.
Singh, R. S., and R. J. Kulathinal. 2000. Sex gene pool evolution and speciation: a new paradigm. Genes Genet. Syst. 75:119-130.[CrossRef][ISI][Medline]
Swanson, W. J., R. Nielsen, and Q. Yang. 2003. Pervasive adaptive evolution in mammalian fertilization proteins. Mol. Biol. Evol. 20:18-20.
Swanson, W. J., and V. D. Vacquier. 2002. The rapid evolution of reproductive proteins. Nat. Rev. Genet. 3:137-144.[CrossRef][ISI][Medline]
Thornton, K., and M. Long. 2002. Rapid divergence of gene duplicates on the Drosophila melanogaster X chromosome. Mol. Biol. Evol. 10:918-925.
Torgerson, D. G., R. J. Kulathinal, and R. S. Singh. 2002. Mammalian sperm proteins are rapidly evolving: evidence of positive selection in functionally diverse genes. Mol. Biol. Evol. 19:1973-1980.
Turelli, M., and D. J. Begun. 1997. Haldane's rule and X-chromosome size in Drosophila. Genetics 147:1799-1815.
Turner, R. M., L. R. Johnson, L. Haig-Ladewig, G. L. Gerton, and S. B. Moss. 1998. An X-linked gene encodes a major human sperm fibrous sheath protein, hAKAP82: genomic organization, protein kinase A-RII binding, and distribution of the precursor in the sperm tail. J. Biol. Chem. 273:32135-32141.
Wang, P. J., J. R. McCarrey, F. Yang, and D. C. Page. 2001. An abundance of X-linked genes expressed in spermatogonia. Nat. Genet. 27:422-426.[CrossRef][ISI][Medline]
Wolfe, K. H., and P. M. Sharp. 1993. Mammalian gene evolution: nucleotide sequence divergence between mouse and rat. J. Mol. Evol. 37:441-456.[ISI][Medline]
Zeng, L. W., and R. S. Singh. 1993. The genetic basis of Haldane's rule and the nature of asymmetric hybrid male sterility among Drosophila simulans, Drosophila mauritiana, and Drosophila sechellia. Genetics 134:251-260.
Zhang, J., and M. Nei. 2000. Positive selection in the evolution of mammalian interleukin-2 genes. Mol. Biol. Evol. 17:1413-1416.