Playing Hide-and-Seek in Beta-Globin Genes: Gene Conversion Transferring a Beneficial Mutation between Differentially Expressed Gene Duplicates

Increasing evidence suggests that adaptation to diverse environments often involves selection on existing variation rather than new mutations. A previous study identified a nonsynonymous single nucleotide polymorphism (SNP) in exon 2 of two paralogous β-globin genes of the bank vole (Clethrionomys glareolus) in Britain in which the ancestral serine (Ser) and the derived cysteine (Cys) allele represent geographically partitioned functional variation affecting the erythrocyte antioxidative capacity. Here we studied the geographical pattern of the two-locus Ser/Cys polymorphism throughout Europe and tested for the geographic correlation between environmental variables and allele frequency, expected if the polymorphism was under spatially heterogeneous environment-related selection. Although bank vole population history clearly is important in shaping the dispersal of the oxidative stress protective Cys allele, analyses correcting for population structure suggest the Europe-wide pattern is affected by geographical variation in environmental conditions. The β-globin phenotype is encoded by the major paralog HBB-T1 but we found evidence of bidirectional gene conversion of exon 2 with the low-expression paralog HBB-T2. Our data support the model where gene conversion reshuffling genotypes between high- and low- expressed paralogs enables tuning of erythrocyte thiol levels, which may help maintain intracellular redox balance under fluctuating environmental conditions. Therefore, our study suggests a possible role for gene conversion between differentially expressed gene duplicates as a mechanism of physiological adaptation of populations to new or changing environments.