title: Remarkably ancient balanced polymorphisms in a multi-locus gene network.
abstract: 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. Here we report a previously unrecognized type of intraspecific multi-locus genetic variation that has been maintained over a vast period. The galactose (GAL) utilization gene network of Saccharomyces kudriavzevii, a relative of brewer's yeast, exists in two distinct states: a functional gene network in Portuguese strains and, in Japanese strains, a non-functional gene network of allelic pseudogenes. Genome sequencing of all available S. kudriavzevii strains revealed that none of the functional GAL genes were acquired from other species. Rather, these polymorphisms have been maintained for nearly the entire history of the species, despite more recent gene flow genome-wide. Experimental evidence suggests that inactivation of the GAL3 and GAL80 regulatory genes facilitated the origin and long-term maintenance of the two gene network states. This striking example of a balanced unlinked gene network polymorphism introduces a remarkable type of intraspecific variation that may be widespread.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Chris Todd
authors.initials: CT
authors.lastname: Hittinger
authors.forename: Paula
authors.initials: P
authors.lastname: Gonçalves
authors.forename: José Paulo
authors.initials: JP
authors.lastname: Sampaio
authors.forename: Jim
authors.initials: J
authors.lastname: Dover
authors.forename: Mark
authors.initials: M
authors.lastname: Johnston
authors.forename: Antonis
authors.initials: A
authors.lastname: Rokas
mesh_terms: D000483:Alleles; D019143:Evolution, Molecular; D005690:Galactose / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics*; D016681:Genome, Fungal; D007564:Japan; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic / Q000235:genetics*; D011174:Portugal; D011544:Pseudogenes / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012440:Saccharomyces / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D005690:Galactose