balanced polymorphism - senecio7の日記

Hittinger CT, Gonçalves P, Sampaio JP, Dover J, Johnston M & Rokas A 2010 Remarkably ancient balanced polymorphisms in a multi-locus gene network. Nature 464:54-58.

local adaptations within species are often governed by several interacting genes scattered throughout the genome
single-locus models of selection cannot explain the maintenance of such complex variation because recombination separates co-adapted alleles

quantitative genetic analyses have revealed numerous instances where ecologically relevant traits are sculpted from variation at multiple loci
often through epistatic interactions between genes

here we report a previously unrecognized type of balanced polymorphism that we term a 'balanced unlinked gene network polymorphism' (BuGNP)
consisting of co-adapted alleles of several functionally related, unlinked genes with extremely elevated sequence divergence
the BuGNP we describe has persisted for nearly the entire history of the species
even as gene flow continued throughout the rest of the genome
BuGNPs can persist over vast periods without speciation
their interacting genes comprise alternative network states that are most effective at performing a coordinated task when their allelic states are matched

the key features of the GAL gene network are preserved among most members of the genus Saccharomyces sensu stricto (hereafter referred to as Saccharomyces) that includes S. cerevisiae and its close relative, S. kudriavzevii
the type strain of S. kudriavzevii and several more distantly related species have independently lost functional GAL genes, resulting in their inability to use galactose as a carbon source
the genomes of the S. kudriavzevii type strain and of three other strains isolated in Japan possess heavily degenerated GAL pseudogenes that are syntenic with the functional GAL genes of the other Saccharomyces species
in several Portuguese locations and substrates, 14 strains of S. kudriavzevii that can use galactose (Gal⁺ strains) as their sole carbon source

the coalescence of the GAL pseudogenes and functional GAL genes occurred near the time of divergence of S. kudriavzevii as a distinct lineage
the GAL pseudogenes are about 89% as old as the
this finding is remarkable, given the lack of any apparent pre-zygotic or post-zygotic barrier to crosses between Gal⁺ and Gal⁻ S. kudriavzevii strains in the laboratory

all strains share a recent common ancestor for nearly all genes, with coalescence at only 3% of the way back in the S. kudriavzevii lineage, except for the Gal⁻ Japanese strain IFO1803
this highly divergent strain is an outgroup to all other strains of S. kudriavzevii except at the GAL loci, where it is monophyletic with the other Japanese strains

in addition to the GAL loci, 48 other genes are significantly more divergent than the genome average and are thus good candidates for genes under balancing selection

we wondered whether some combinations of functional and pseudogene alleles might make cells unfit in environments that lack galactose
the absence of the Gal80 co-repressor in a Gal⁻ population is expected to lead to constitutive, deleterious expression of partial GAL gene networks in strains containing invading functional alleles of GAL4 and any GAL target genes
S. kudriavzevii gal80Δ mutants containing functional alleles of the rest of the GAL genes were at a significant disadvantage when grown without galactose
thus, in genetic backgrounds that cause partial gene networks to be expressed constitutively (that is, GAL4⁺ gal80Δ strains), functional GAL alleles (other than GAL80) would be strongly selected against
thereby imposing a moderate fitness cost when averaged across all genetic backgrounds that an allele might encounter in the absence of galactose