Academic journal article Genetics

Altitudinal Variation at Duplicated [Beta]-Globin Genes in Deer Mice: Effects of Selection, Recombination, and Gene Conversion

Academic journal article Genetics

Altitudinal Variation at Duplicated [Beta]-Globin Genes in Deer Mice: Effects of Selection, Recombination, and Gene Conversion

Article excerpt

ABSTRACT Spatially varying selection on a given polymorphism is expected to produce a localized peak in the between-population component of nucleotide diversity, and theory suggests that the chromosomal extent of elevated differentiation may be enhanced in cases where tandemly linked genes contribute to fitness variation. An intriguing example is provided by the tandemly duplicated b-globin genes of deer mice (Peromyscus maniculatus), which contribute to adaptive differentiation in blood-oxygen affinity between high- and low-altitude populations. Remarkably, the two b-globin genes segregate the same pair of functionally distinct alleles due to a history of interparalog gene conversion and alleles of the same functional type are in perfect coupling-phase linkage disequilibrium (LD). Here we report a multilocus analysis of nucleotide polymorphism and LD in highland and lowland mice with different genetic backgrounds at the b-globin genes. The analysis of haplotype structure revealed a paradoxical pattern whereby perfect LD between the two b-globin paralogs (which are separated by 16.2 kb) is maintained in spite of the fact that LD within both paralogs decays to background levels over physical distances of less than 1 kb. The survey of nucleotide polymorphism revealed that elevated levels of altitudinal differentiation at each of the b-globin genes drop away quite rapidly in the external flanking regions (upstream of the 59 paralog and downstream of the 39 paralog), but the level of differentiation remains unexpectedly high across the intergenic region. Observed patterns of diversity and haplotype structure are difficult to reconcile with expectations of a two-locus selection model with multiplicative fitness.

WHEN functionally distinct alleles are maintained as a balanced polymorphism, each of the associated genetic backgrounds accumulates its own set of neutral mutations. The partitioning of nucleotide variation between alternative allele classes results in elevated levels of diversity and linkage disequilibrium (LD), and this characteristic signature provides a possible means of identifying balanced polymorphisms in genomic survey data (Charlesworth 2006). The chromosomal extent of the elevated diversity and haplotype structure is jointly determined by the age of the selected polymorphism and the frequency of crossing over, as recombination provides a conduit for genetic exchange between alternative allele classes (Strobeck 1983; Hudson and Kaplan 1988; Kaplan et al. 1988; Schierup et al. 2000; Charlesworth et al. 2003; Nordborg and Innan 2003; Wiuf et al. 2004). In the case of spatially varying selection, alternative alleles will be present at different frequencies in locally adapted populations. This increases between- population components of diversity and LD relative to within-population components. Consequently, spatially varying selection on a given polymorphism is expected to produce a localized peak of between-population diversity, and the elevated differentiation at linked sites will decline as a function of genetic map distance from the selected site (Charlesworth et al. 1997; Feder and Nosil 2010).

Over a broad range of population sizes and migration rates, recombination is expected to limit the peak of differentiation to a relatively narrow window spanning the selected polymorphism (Feder and Nosil 2010). The signature of selection may be further eroded by gene conversion, which provides a second conduit for genetic exchange between selectively maintained allele classes. Peaks of differentiation may be most readily detectable in cases where epistatic selection maintains coadapted combinations of alleles at linked genes. This is because the selective elimination of recombinant chromosomes reduces the effective rate of crossing over between the selected loci (Ishii and Charlesworth 1977). In cases in which two or more linked genes jointly contribute to fitness variation, theoretical results suggest that it may be possible to detect the effects of epistatic selection by analyzing patterns of silent-site diversity in the intergenic region and in the external flanking regions (Kelly 2000; Kelly and Wade 2000; Barton and Navarro 2002; Navarro and Barton 2002; Chevin et al. …

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