Pronounced Differences of Recombination Activity at the Sex Determination Locus of the Honeybee, a Locus Under Strong Balancing Selection

Abstract

Recombination decreases the association of linked nucleotide sites and can influence levels of polymorphism in natural populations. When coupled with selection, recombination may relax potential conflict among linked genes, a concept that has played a central role in research on the evolution of recombination. The sex determination locus (SDL) of the honeybee is an informative example for exploring the combined forces of recombination, selection, and linkage on sequence evolution. Balancing selection at SDL is very strong and homozygous individuals at SDL are eliminated by worker bees. The recombination rate is increased up to four times that of the genomewide average in the region surrounding SDL. Analysis of nucleotide diversity (p) reveals a sevenfold increase of polymorphism within the sex determination gene complementary sex determiner (csd) that rapidly declines within 45 kb to levels of genomewide estimates. Although no recombination was observed within SDL, which contains csd, analyses of heterogeneity, shared polymorphic sites, and linkage disequilibrium (LD) show that recombination has contributed to the evolution of the 59 part of some csd sequences. Gene conversion, however, has not obviously contributed to the evolution of csd sequences. The local control of recombination appears to be related to SDL function and mode of selection. The homogenizing force of recombination is reduced within SDL, which preserves allelic differences and specificity, while the increase of recombination activity around SDL relaxes conflict between SDL and linked genes.

Origin of a function by tandem gene duplication limits the evolutionary capability of its sister copy

“…Balancing selection at csd also increased the maintenance time of linked loci, resulting in an accumulation of more mutations, which we detected as an increase in polymorphism (16). The intron nucleotide diversity of fem in current A. mellifera populations is higher than the genome-wide average diversity (Table 3).…”

“…Within the genomic region of the sex determination locus (SDL), recombination is substantially reduced compared with the adjacent genomic regions, which, conversely, show a significant increase in recombinational exchange (up to 70 cM/Mb) compared with the genome-wide average (16). A decline in silent polymorphism when moving toward the 5′ part of the csd gene (16) indicates that meiotic recombination is operating; however, this reflects a process over prolonged evolutionary time due to extended maintenance times of alleles. These rare recombination events within the SDL explain the reduced association between fem and csd polymorphism over 12 kb.…”

“…We also studied the evolution of fem in today's honey bee population by analyzing nucleotide polymorphism. Balancing selection acting at the csd gene maintains 16 times more nucleotide diversity than the genome-wide average (13,16). Alleles of csd are seldom lost through the process of genetic drift and are maintained over extended periods, during which they accumulate numerous synonymous mutations (17).…”

“…Alleles of csd are seldom lost through the process of genetic drift and are maintained over extended periods, during which they accumulate numerous synonymous mutations (17). We have previously shown that the nucleotide diversity of neutral linked loci decreases gradually with physical distance of 1.5-45 kb to csd (16). We compared the nucleotide diversity (π) of fem, csd, and the genome-wide average in A. mellifera to examine whether genetic linkage to csd could elevate the level of nucleotide diversity of fem.…”

How closely does genetic diversity in finite populations conform to predictions of neutral theory? Large deficits in regions of low recombination

“…For example, loci near self-incompatibility loci (that are subject to frequency-dependent selection) in Arabidopsis lyrata, but not involved in self-incompatibility themselves, have elevated levels of genetic diversity compared with other loci in the genome (Kamau et al, 2007;Ruggiero et al, 2008). Similarly, the major histocompatibility complex in vertebrates and the complementary sex-determining locus in Hymenoptera are both subject to balancing selection, and flanking sequences that are not themselves subject to selection also show elevated levels of genetic diversity (O'hUigin et al, 2000;Hasselmann and Beye, 2006).…”