Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden
Correspondence: E-mail: hans.ellegren{at}ebc.uu.se.
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Abstract |
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Key Words: sex chromosomes effective population size male mutation bias selective sweeps background selection
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Introduction |
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A number of studies have shown that levels of nucleotide diversity on the human Y chromosome are lower than in the rest of the genome (Malaspina et al. 1990; Dorit, Akashi, and Gilbert 1995; Hammer 1995; Whitfield, Sulston, and Goodfellow 1995; Nachman 1998; Anagnostopoulos et al. 1999; Jaruzelska, Zietkiewicz, and Labuda 1999; Shen et al. 2000; The International SNP Map Working Group 2001). This lower incidence of nucleotide diversity may be related to human biologye.g., sex differences in patterns of migration or biased matingbut may also reflect a general feature of mammalian Y chromosomes or, even more generally, of species with male heterogamety. To address the generality of low Y chromosome variability, we initiated screening for single-nucleotide poplymorphisms (SNPs) in noncoding sequence from the Y chromosome of five mammalian species: lynx (Lynx lynx), wolf (Canis lupus), reindeer (Rangifer tarandus), cattle (Bos taurus), and field vole (Microtus agrestis). Taxonomically, these species are spread in the mammalian phylogenetic tree, and they also differ in terms of population history and mating system. To be able to compare Y chromosome variability with a measure of nucleotide diversity in other parts of the genome from each of the species, which are poorly characterized in terms of intraspecific levels of polymorphism, we also screened for SNPs in noncoding X chromosome DNA sequences. Here we show that lower than expected levels of Y-linked nucleotide diversity are found in all five species, indicating that reduced levels of Y chromosome polymorphism may be a generalized feature of mammalian genomes.
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Materials and Methods |
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Results and Discussion |
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Although differences in effective population size should thus be expected to lead to low levels of Y chromosome variability, differences in chromosome-specific mutation rates should have the opposite effect, given that µY is typically higher than µX as a result of male-biased mutation (Hurst and Ellegren 1998; Li, Yi, and Makova 2002), and perhaps other factors affecting chromosome-specific mutation rates (Lercher, Williams, and Hurst 2001). Species-specific estimates of the male-to-female mutation rate ratio (m) are not available for the species presented here, but some indication is given by data from other mammals. The most recent estimate of human
m is at a factor of 5 (Makova and Li 2002). In Felidaei.e., including the lynxPecon-Slattery and O'Brien (1998) estimated
m at 4. For rodents,
m is estimated at about 2 (Chang et al. 1994; Chang and Li 1995). The extent of the male bias is likely to be positively correlated with generation time (Chang et al. 1994; Li et al. 1996; Bartosch-Härlid et al. 2003), and available data would thus suggest that mammalian
m ranges approximately from 2 (short-lived species like most rodents) to 5 (humans). Here, we assume
m
4 in wolf, cattle, lynx, and reindeer, and
2 in field vole. The corresponding µY/µX ratios are 2.0 and 1.5, respectively [note that µY/µX =
m/(1/3
m + 2/3)]. Now, combining the effects of differences in effective population size and mutation rate (
X/
Y = 3µX/µY), we should expect 1.5 times higher nucleotide diversity on X than on Y for wolf, cattle, lynx, and reindeer, and 2.0 times higher for field vole.
Any deviation from the expected difference in nucleotide diversity between X and Y would suggest that other factors are differentially affecting polymorphism levels on the two sex chromosomes. Figure 1 shows the adjusted levels of nucleotide diversity on X when differences in effective population size and mutation rate have been accounted for (i.e., when X is divided by 1.5 for wolf, cattle, lynx, and reindeer, and by 2.0 for field vole). The three species monomorphic for Ylynx, cattle, and reindeerobviously remain less variable on Y than on X; for these species the lower 95% confidence interval for
X does not include 0. Unfortunately, the absence of observed polymorphism on Y prevents statistical analysis of Y chromosome data. For the two species with observed polymorphism on Ywolf and field volenucleotide diversity also remains lower on Y than on X after compensating for differences in effective population size and mutation rate (fig. 1), although there is overlap in the 95% confidence intervals for
X and
Y. In summary, our data reveal a general trend of lower than expected levels of nucleotide diversity in mammalian Y chromosomes.
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The effective population size of Y will be lowered by a high variance in male reproductive success (relative to that of females) (Caballero 1995; Nagylaki 1995; Charlesworth 1996). This may occur in polygynous species (Greenwood 1980), where a few males father a disproportionably large fraction of all offspring. One particular situation when this should apply is in the case of domestic animals; for most of these species, a limited number of males is typically used in breeding programs. The low levels of Y chromosome variability that we found in cattle could be attributed, at least in part, to a strong sex bias in breeding. Another mechanism that has been suggested to lower the effective population size of males is deleterious mutations in mitochondrial DNA (mtDNA) (Gemmel and Sin 2002). Because energy demand for spermatogenesis and sperm motility is very high, much higher than for oogenesis, and because the main function of mitochondrion is to produce ATP through oxidative phosphorylation, sperm may be particularly sensitive to mutations in mtDNA. Such sensitivity could lead to impaired sperm function and thereby lowered male reproductive success.
The nucleotide diversity of the human Y chromosome is about 20% of that found in autosomes (Shen et al. 2000; The International SNP Map Working Group 2001). This is less than expected when differences in effective population size and mutation rate are taken into account. [The International SNP Map Working Group (2001) predicts that Y would have a diversity 31% that of the autosomes; however, they use an m estimate of 1.7 based on Bohossian, Skaletsky, and Page (2000), while a more recent study has estimated
m at 5 (Makova and Li 2002). Using the latter estimate we should expect nucleotide diversity on Y be 42% that of the autosomes, thus strengthening the interpretation of lower than expected variability on human Y.] Together with the extensive data available from the human genome, and reports of comparatively low levels of Y chromosome variability in apes (Hammer 1995; Burrows amd Ryder 1997; Stone et al. 2002), our data thus indicate that the mammalian Y chromosome may generally have reduced levels of genetic variability. Moreover, similar observations have been made for Y chromosomes of Drosophila (McAllister and Charlesworth 1999; Bachtrog and Charlesworth 2000) and even of plants (Filatov et al. 2000, 2001). Furthermore, in birds, which have a reversed sex chromosome organization characterized by female heterogamety (females ZW, males ZZ), the W chromosome is very low in nucleotide diversity (Montell, Fridolfsson, and Ellegren 2001; Berlin and Ellegren 2001). These combined data would suggest that a reduced level of genetic variability is a common feature of the sex-limited chromosome (Ellegren 2003), in turn suggesting a common mechanism underlying this phenomenon. Of the potential causative factors listed above, we note that selection is the only one that is broadly applicable irrespective of mode of reproduction or whether there is male or female heterogamety. [High variance in male reproductive success cannot explain the low levels of variability in the female-specific W chromosomes of birds, and lowered male effective population size due to mutations in mtDNA is not applicable to avian and plant systems.] We therefore favor the idea that selection is a key factor in the evolution of nucleotide diversity on the sex-limited chromosome. Unravelling the relative importance of, on the one hand, background selection and, on the other, selective sweeps in shaping genetic variability on the sex-limited chromosome will be an important question for future research in this area.
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Acknowledgements |
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Footnotes |
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