Trends in Genetics
Volume 25, Issue 6, June 2009, Pages 278-284
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Review
The different levels of genetic diversity in sex chromosomes and autosomes

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Sex chromosomes and autosomes differ in their effective population size, mutation and demography, all of which affect the relative level of genetic diversity within the genome. Moreover, natural selection acts differentially on the two chromosomal categories, for example, because recessive mutations are directly exposed to selection on the single X chromosome of males. Recent genome analyses reveal a heterogeneous picture of the sex-chromosome-to-autosome diversity ratio in different organisms. Reduced X chromosome diversity has been interpreted to reflect demographic features such as bottlenecks and male-biased dispersal, whereas more equal diversity in sex chromosomes and autosomes has been explained by polygynous mating systems.

Introduction

Genetic diversity within species constitutes the raw material for evolution by natural selection and by factors such as genetic drift, recombination and migration. Improved capacity for DNA sequencing over the past decade has provided us with new insight into the genetic variation of different species and populations. For example, we have learned that our closest living relative, the chimpanzee, is genetically more diverse than our own species, at least when the combined diversity of all populations of each species is considered [1]; in fact, human genetic diversity is at the lower end of the range of diversities so far observed among mammals, testifying to the small size of ancestral human populations (see later).

Population genetics theory stipulates that the amount of genetic diversity is dependent on the rate of mutation and the effective population size (Ne; see Glossary). This implies that within-genome levels of genetic diversity should not be expected to be uniform, for example, because mutation rates vary considerably among different types of DNA sequences and across the genome. Variation in the rate of point mutation is evident at several levels, including sequence context effects such as the highly unstable CpG dinucleotide, and local (kb-level) and regional (Mb-level) mutation rate variation [2]. There is firm empirical support for a close correlation between the local rates of mutation and polymorphism (genetic diversity) 3, 4. Ne also varies across the genome, most notably owing to the influence of natural selection and demography [5]. With low Ne, low diversity usually follows [6].

However, sex chromosomes differ from autosomes in several aspects of their molecular evolution and population genetics 7, 8, 9 and this also holds true when it comes to levels of genetic diversity. In general, the level of genetic diversity on the X chromosome (or the Z chromosome in systems with female heterogamety such as birds) is expected to be lower than on autosomes because of a lower effective population size for the X chromosomes (the default prediction is that Ne of the X = 75% the Ne of autosomes). However, the special mode of inheritance of sex chromosomes (mothers transmit an X chromosome to both sons and daughters, fathers only to daughters) makes the role of mutation, genetic drift, selection, migration, demography and mating system different from the standard situation of biparental inheritance of autosomes in diploid organisms. The combined effect of these evolutionary factors is complex because sometimes they act in opposite directions to levels of diversity and they can have different consequences in male and female heterogamety. The fact that X chromosomes and autosomes might respond differently to different evolutionary factors can help elucidate the relative importance of these factors to molecular evolution. There has been a recent burst of polymorphism datasets from genome re-sequencing studies of multiple populations of different species that now enable us to test empirical data on sequence polymorphism in autosomes and sex chromosomes against theoretical predictions for levels of genetic diversity under different evolutionary scenarios. Here, I review these recent findings to show how nucleotide diversity at neutral sites differs between sex chromosomes and autosomes. I focus on patterns of variation seen in the X and the Z chromosome of organisms with male and female heterogamety; for recent reviews on the evolution of genetic diversity in the uniparentally inherited Y and W chromosomes, which are affected by different evolutionary forces owing to their non-recombining nature, see Refs 10, 11.

Section snippets

The role of neutral factors on diversity levels

A starting point in any evolutionary study aimed at elucidating the role of natural selection on DNA sequence evolution is to define the neutral expectations. I therefore begin by discussing neutral factors affecting diversity levels on sex chromosomes and autosomes.

The role of natural selection on diversity levels

Background selection (purifying selection against deleterious alleles) [27] and selective sweeps (positive selection for beneficial variants) [28] both have the effect of reducing nucleotide diversity at linked sites. The strength of this effect is dependent on the rate of recombination between a selected locus and a neighbouring region; essentially, the effect becomes more pronounced with less recombination because of linkage disequilibrium between adjacent loci. Given that the sex chromosomes

Empirical observations

Most studies analysing the sex-chromosome–autosome diversity ratio have focused on humans and flies (Table 1). One immediate observation that can be made from a comparison of these studies is that there is pronounced variation in the estimated X:A ratio within species. For example, the estimated X:A diversity ratio in humans ranges between 0.60 and 1.05. There are several possible explanations for this heterogeneity. The amount of sequence analysed equals 1 and it is noteworthy that all recent

Concluding remarks

There is currently considerable interest in detecting signatures of adaptation in DNA sequence data, either using comparative genomic (interspecific comparisons) or population genetic (intraspecific comparisons) approaches, or a combination of both 50, 51, 52, 53. Comparing sex-linked and autosomal variation can be motivated by the same interest because we might expect selection to differentially affect genetic diversity in sex chromosomes and autosomes. On the one hand, making inferences about

Acknowledgements

Financial support was obtained from the Swedish Research Council. I thank Carina Mugal for help with Box 1, and Niclas Backström, Ammon Corl, Carina Mugal, Benoit Nabholz and Kiwoong Nam for useful discussion.

Glossary

Effective population size (Ne)
the number of breeding individuals in an idealized population that would show the same degree of genetic drift or inbreeding as the actual population.
Sexual selection
competition among individuals of one sex, usually males, for reproductive access to the other sex, usually females.
Sperm competition
when females mate with more than one male, there will be competition among sperm from the different males to succeed in fertilization.
Linkage disequilibrium
the non-random

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