Contribution of a mutational hot spot to hemoglobin adaptation in high-altitude Andean house wrens

Abstract

A key question in evolutionary genetics is why certain mutations or certain types of mutation make disproportionate contributions to adaptive phenotypic evolution. In principle, the preferential fixation of particular mutations could stem directly from variation in the underlying rate of mutation to function-altering alleles. However, the influence of mutation bias on the genetic architecture of phenotypic evolution is difficult to evaluate because data on rates of mutation to function-altering alleles are seldom available. Here, we report the discovery that a single point mutation at a highly mutable site in the β A -globin gene has contributed to an evolutionary change in hemoglobin (Hb) function in high-altitude Andean house wrens (Troglodytes aedon). Results of experiments on native Hb variants and engineered, recombinant Hb mutants demonstrate that a nonsynonymous mutation at a CpG dinucleotide in the β A -globin gene is responsible for an evolved difference in Hb-O 2 affinity between high-and low-altitude house wren populations. Moreover, patterns of genomic differentiation between high-and low-altitude populations suggest that altitudinal differentiation in allele frequencies at the causal amino acid polymorphism reflects a history of spatially varying selection. The experimental results highlight the influence of mutation rate on the genetic basis of phenotypic evolution by demonstrating that a large-effect allele at a highly mutable CpG site has promoted physiological differentiation in blood O 2 transport capacity between house wren populations that are native to different elevations.biochemical adaptation | hemoglobin | high altitude | hypoxia | mutation bias

Mutation-biased adaptation in Andean house wrens

“…Surely there are other ways to adapt, and other ways to adapt by increasing affinity, given that previous studies (cited by Galen et al) found other hemoglobin mutations that increase affinity in high-altitude species; indeed, the authors themselves discovered a different affinity-increasing mutant at a low frequency in house wrens (see figure 4 in ref. 1). We see the Val-to-Ile change, not because it is the fittest alternative, but because it is so strongly favored by the "arrival of the fittest."…”

“…This influence is typically attributed to neutral evolution, presuming that mutation is a weak force easily overcome by selection, so that any noticeable effect of mutation must signal a lack of selection. However, in PNAS Galen et al (1) propose a case of mutation-biased adaptation, in which the course of evolution reflects both a bias in mutation and a fitness benefit. How important are mutational biases in shaping adaptation?…”

“…Galen et al (1) report detailed molecular and biogeographic evidence for an adaptation to altitude in Andean house wrens (Troglodytes aedon) involving hemoglobin, a protein with a central role in oxygen transport. In this species, site 55 of the β-chain of hemoglobin has either Val (valine), which is the ancestral amino acid, or Ile (isoleucine).…”

“…See companion article on page 13958. 1 To whom correspondence should be addressed. Email: arlin@ umd.edu.…”

Neutral and functionally important genes shed light on phylogeography and the history of high‐altitude colonization in a widespread New World duck

“…For example, estimates of gene flow between lowland and highland populations of Crested Ducks ( Lophonetta specularioides ) obtained based on hemoglobin alleles are much lower than those inferred from neutral markers; in light of biochemical properties of amino acid substitutions differing across elevations, such differences in hemoglobin gene flow are consistent with a role for selection structuring genetic and phenotypic variation (Bulgarella et al., 2012). Likewise, hemoglobin variants with increased affinity for oxygen occur at a greater frequency in high‐elevation populations of House Wrens ( Troglodytes aedon ) relative to those from lowland areas, and F st across elevations for a functionally important site in the βA‐globin gene is greater than F st values for most coding SNPs across the genome (Galen et al., 2015). Because the high‐elevation βA‐globin genotype is derived, colonization of high‐elevation environments by House Wrens presumably involved adaptive evolution in protein function.…”