To investigate mutation-rate variation between autosomes and sex chromosomes in the avian genome, we have analyzed divergence between chicken (Gallus gallus) and turkey (Meleagris galopavo) sequences from 33 autosomal, 28 Z-linked, and 14 W-linked introns with a total ungapped alignment length of approximately 43,000 bp. There are pronounced differences in the mean divergence among autosomes and sex chromosomes (autosomes [A] = 10.08%, Z chromosome = 10.99%, and W chromosome = 5.74%), and we use these data to estimate the male-to-female mutation-rate ratio (alpha(m)) from Z/A, Z/W, and A/W comparisons at 1.71, 2.37, and 2.52, respectively. Because the alpha(m) estimates of the three comparisons do not differ significantly, we find no statistical support for a specific reduction in the Z chromosome mutation rate (Z reduction estimated at 4.89%, P = 0.286). The idea of mutation-rate reduction in the sex chromosome hemizygous in one sex (i.e., X in mammals, Z in birds) has been suggested on the basis of theory on adaptive mutation-rate evolution. If it exists in birds, the effect would, thus, seem to be weak; a preliminary power analysis suggests that it is significantly less than 18%. Because divergence may vary within chromosomal classes as a result of variation in mutation and/or selection, we developed a novel double-bootstrapping method, bootstrapping both by introns and sites from concatenated alignments, to estimate confidence intervals for chromosomal class rates and for alpha(m). The narrowest interval for the alpha(m) estimate is 1.88 to 2.97 from the Z/W comparison. We also estimated alpha(m) using maximum likelihood on data from all three chromosome classes; this method yielded alpha(m) = 2.47 and approximate 95% confidence intervals of 2.27 to 2.68. Our data are broadly consistent with the idea that mutation-rate differences between chromosomal classes can be explained by the male mutation bias alone.

Understanding the population genetic factors that shape genome variability is pivotal to the design and interpretation of studies using large-scale polymorphism data. We analyzed patterns of polymorphism and divergence at Z-linked and autosomal loci in the domestic chicken (Gallus gallus) to study the influence of mutation, effective population size, selection, and demography on levels of genetic diversity. A total of 14 autosomal introns (8316 bp) and 13 Z-linked introns (6856 bp) were sequenced in 50 chicken chromosomes from 10 highly divergent breeds. Genetic variation was significantly lower at Z-linked than at autosomal loci, with one segregating site every 39 bp at autosomal loci ( W ϭ 5.8 Ϯ 0.8 ϫ 10 Ϫ3 ) and one every 156 bp on the Z chromosome ( W ϭ 1.4 Ϯ 0.4 ϫ 10 Ϫ3). This difference may in part be due to a low male effective population size arising from skewed reproductive success among males, evident both in the wild ancestor-the red jungle fowl-and in poultry breeding. However, this effect cannot entirely explain the observed three-to fourfold reduction in Z chromosome diversity. Selection, in particular selective sweeps, may therefore have had an impact on reducing variation on the Z chromosome, a hypothesis supported by the observation of heterogeneity in diversity levels among loci on the Z chromosome and the lower recombination rate on Z than on autosomes. Selection on sex-linked genes may be particularly important in organisms with female heterogamety since the heritability of sex-linked sexually antagonistic alleles advantageous to males is improved when fathers pass a Z chromosome to their sons. S INGLE-NUCLEOTIDE polymorphisms (SNPs) conWithin-genome variation in SNP frequency is likely stitute a primary source of the variability that underto occur at several different scales. To name but one lies differences in the genetic make-up of individuals reason, hot-spot sites for mutation as well as mutation within species. Currently, the application of SNPs to rate variation at larger scales imply heterogeneity in the genomics and population genetics is rapidly expanding distribution of SNPs (Ebersberger et al. 2002; Internaand evidence of significant variation in the density of SNPs 2003). Population genetics theory stipulates that the along chromosomes. There is also the potential of variadegree and character of genetic variability are governed tion in SNP frequency between chromosomes and this by factors such as mutation, selection, and effective popapplies in particular to differences between autosomes ulation size. Understanding the role of these factors in and sex chromosomes (Begun and Whitley 2000; Inshaping patterns of polymorphism within genomes is ternational SNP Map Working Group 2001). These key to the interpretation of SNP data in, for example, chromosome classes differ with respect to several of association studies and for the quantification of linkage the factors thought to affect nucleotide diversity and disequilibrium (LD) through analysis of haplotype dicontrasting the...

The rate of mutation for nucleotide substitution is generally higher among males than among females, likely owing to the larger number of DNA replications in spermatogenesis than in oogenesis. For insertion and deletion (indel) mutations, data from a few human genetic disease loci indicate that the two sexes may mutate at similar rates, possibly because such mutations arise in connection with meiotic crossing over. To address origin- and sex-specific rates of indel mutation we have conducted the first large-scale molecular evolutionary analysis of indels in noncoding DNA sequences from sex chromosomes. The rates are similar on the X and Y chromosomes of primates but about twice as high on the avian Z chromosome as on the W chromosome. The fact that indels are not uncommon on the nonrecombining Y and W chromosomes excludes meiotic crossing over as the main cause of indel mutation. On the other hand, the similar rates on X and Y indicate that the number of DNA replications (higher for Y than for X) is also not the main factor. Our observations are therefore consistent with a role of both DNA replication and recombination in the generation of short insertion and deletion mutations. A significant excess of deletion compared to insertion events is observed on the avian W chromosome, consistent with gradual DNA loss on a nonrecombining chromosome.