Evidence That the Human X Chromosome Is Enriched for Male-Specific but not Female-Specific Genes

Lercher, Martin J.

doi:10.1093/molbev/msg131

Cited by 117 publications

(96 citation statements)

References 17 publications

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“…The accumulation of both male-and female-biased genes on the X chromosome is consistent with the predictions of W. Rice 3 and previous reports on mice and humans [6][7][8] . We believe that the paucity of testis-enriched genes on the mouse X is mainly attributable to the effects of MSCI 19,20 .…”

supporting

confidence: 91%

“…One model predicts that genes with sexbiased expression should be enriched on the X chromosome [2][3][4][5] . In agreement with Rice's hypothesis 3 , spermatogonial genes are over-represented on the X chromosome of mice 6 and sex-and reproduction-related genes are over-represented on the human X chromosome 7,8 . Male-biased genes are under-represented on the X chromosome in worms and flies [9][10][11] , however.…”

supporting

confidence: 86%

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The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation

et al. 2004

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Sex chromosomes are subject to sex-specific selective evolutionary forces 1,2 . One model predicts that genes with sexbiased expression should be enriched on the X chromosome 2-5 . In agreement with Rice's hypothesis 3 , spermatogonial genes are over-represented on the X chromosome of mice 6 and sex-and reproduction-related genes are over-represented on the human X chromosome 7,8 . Male-biased genes are under-represented on the X chromosome in worms and flies 9-11 , however. Here we show that mouse spermatogenesis genes are relatively underrepresented on the X chromosome and female-biased genes are enriched on it. We used Spo11 -/-mice blocked in spermatogenesis early in meiosis 12 to evaluate the temporal pattern of gene expression in sperm development. Genes expressed before the Spo11 block are enriched on the X chromosome, whereas those expressed later in spermatogenesis are depleted. Inactivation of the X chromosome in male meiosis may be a universal driving force for X-chromosome demasculinization.To investigate the genomic distribution of mouse genes with patterns of sex-biased expression, we analyzed the chromosomal distribution of genes expressed in sexually dimorphic tissues. We consider genes that are preferentially expressed in such tissues as testis, ovary and placenta to be sex-biased genes. We used two approaches to define the tissue specificity of genes expressed in mice: analysis of large-scale microarray-based gene expression data and analysis of the distribution of expressed-sequence tags (ESTs) in different cDNA libraries. Instead of focusing on transcripts restricted to a single tissue, our analysis targeted the identification of tissue-enriched transcripts using a 'preferential expression measure' (PEM) 13 . As an uniform source of expression data, we used publicly available data sets of mouse RNA samples representing 49 tissues hybridized to Affymetrix mouse U74A microarrays (GNF data set) 14 and 20 tissues analyzed with RIKEN cDNA microarrays (RIKEN data set) 15 .In the GNF data set 14 , expression of 624 genes (∼7% of all analyzed) in testis was three times greater than the median expression in other tissues, and expression of 361 genes in testis was five times greater (PEM values >1.58 and >2.32, respectively). These genes are considered testis-enriched genes. The chromosomal distribution of testisenriched genes was significantly different from uniform (χ 2 = 30.8, P = 0.05; Fig. 1a and Supplementary Table 1 online). The most significant deviation from the average gene density was on the X chromosome, where testis-enriched genes were 2.5 times less dense (the ratio of the density of testis-enriched genes on the X chromosome to the average density on all chromosomes, ρ X , was 0.40; χ 2 = 7.7, P = 0.006). The depletion of testis-enriched genes on the X chromosome was independent of the cut-off (three or five times greater expression) used in the selection process (Table 1). In addition, genes that were expressed most highly in testis and all the genes detected in testis were underrepresen...

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supporting

confidence: 91%

supporting

confidence: 86%

The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation

et al. 2004

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“…Cold (Wang et al 2001;Lercher et al 2003) because of X inactivation during male meiosis. Preliminary studies in birds show the opposite pattern, with male-biased genes overrepresented on the chicken Z chromosome (Kaiser and Ellegren 2006;Storchova and Divinia 2006), possibly because of incomplete dosage compensation in birds (Itoh et al 2007).…”

Section: Genome Research 621mentioning

confidence: 99%

Fast-X on the Z: Rapid evolution of sex-linked genes in birds

Mank¹,

Axelsson²,

Ellegren³

2007

Genome Res.

155

132

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Theoretical work predicts natural selection to be more efficient in the fixation of beneficial mutations in X-linked genes than in autosomal genes. This "fast-X effect" should be evident by an increased ratio of nonsynonymous to synonymous substitutions (d N /d S ) for sex-linked genes; however, recent studies have produced mixed support for this expectation. To make an independent test of the idea of fast-X evolution, we focused on birds, which have female heterogamety (males ZZ, females ZW), where analogous arguments would predict a fast-Z effect. We aligned 2.8 Mb of orthologous protein-coding sequence of zebra finch and chicken from 172 Z-linked and 4848 autosomal genes. Zebra finch data were in the form of EST sequences from brain cDNA libraries, while chicken genes were from the draft genome sequence. The d N /d S ratio was significantly higher for Z-linked (0.110) than for all autosomal genes (0.085; P = 0.002), as well as for genes linked to similarly sized autosomes 1-10 (0.0948; P = 0.04). This pattern of fast-Z was evident even after we accounted for the nonrandom distribution of male-biased genes. We also examined the nature of standing variation in the chicken protein-coding regions. The ratio of nonsynonymous to synonymous polymorphism (p N /p S ) did not differ significantly between genes on the Z chromosome (0.104) and on the autosomes (0.0908). In conjunction, these results suggest that evolution proceeds more quickly on the Z chromosome, where hemizygous exposure of beneficial nondominant mutations increases the rate of fixation.[Supplemental material is available online at www.genome.org and http://www.egs.uu.se/evbiol/Research/Data/fast-Z/.] Sex chromosomes can exhibit several unusual properties, including inheritance pattern, reduced recombination, and hemizygosity, which influence the mechanisms of natural selection (Rice 1984; Vicoso and Charlesworth 2006). These differences often make evolutionary comparisons between sex chromosomes and autosomes particularly revealing, as they help answer fundamental questions regarding the signature and pattern of mutation and natural selection, as well as how these forces vary across the genome. For instance, consider new autosomal mutations, which are initially low in frequency and primarily present in heterozygotes. If these mutations are either wholly or partially recessive, they will be obscured by the ancestral allele, and will only rarely be exposed directly to selective forces. In contrast, novel recessive and otherwise nondominant mutations on sex chromosomes are directly exposed to selection in the hemizygous sex. Selection would therefore be expected to act faster on sex chromosomes to fix some types of beneficial mutations (Charlesworth et al. 1987), a situation referred to as fast-X evolution.The fast-X (or fast-Z in the case of female heterogamety) effect could potentially explain several evolutionary phenomena. For instance, it has been invoked to explain Haldane's Rule (Haldane 1922), which states that the heterogametic sex suffers highe...

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“…Previous studies indicate that the mammalian X chromosome has an over-representation of premeiotic sperm-expressed genes (Wang et al, 2001;Khil et al, 2004), prostate expressed genes (Lercher et al, 2003), genes involved in cognitive ability (Zechner et al, 2001), brain expressed (Qiu et al, 2002), skeletal muscle expressed (Bortoluzzi et al, 1998), and possibly even tissue-specific expressed genes in general (Lercher et al, 2003). Our data suggest that the X chromosome harbors a higher proportion of positively selected genes, which may offer a more general explanation for the unusually biased gene content of the mammalian X chromosome.…”

Section: Dg Torgerson and Rs Singhmentioning

confidence: 99%

Enhanced adaptive evolution of sperm-expressed genes on the mammalian X chromosome

Torgerson

Singh

2005

Heredity

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Genes on the mammalian X chromosome may be under unique evolutionary pressure due to their hemizygous expression in males. Since any recessive deleterious mutation would immediately be expressed in males and, therefore, efficiently removed from the population, selective constraint could be more pronounced in X-linked genes. Conversely, if a recessive mutation were beneficial, its immediate exposure to selection would be advantageous, and would facilitate adaptive evolution. We tested for positive selection in a total of 86 genes using a maximum likelihood approach, including 40 sperm-expressed and 46 non-sperm, tissue-specific genes. We find evidence to suggest that Xlinkage enhances the effects of positive selection in spermexpressed genes in terms of the number of codons affected, and report a general trend for positively selected genes to reside on the X chromosome rather than on the autosomes. Our data suggest that hemizygous expression in males makes the X chromosome a preferred location for positively selected sperm genes that do not require postmeiotic transcription.

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Evidence That the Human X Chromosome Is Enriched for Male-Specific but not Female-Specific Genes

Cited by 117 publications

References 17 publications

The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation

The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation

Fast-X on the Z: Rapid evolution of sex-linked genes in birds

Enhanced adaptive evolution of sperm-expressed genes on the mammalian X chromosome

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