The role of mutation bias in adaptive molecular evolution: insights from convergent changes in protein function

Abstract

An underexplored question in evolutionary genetics concerns the extent to which mutational bias in the production of genetic variation influences outcomes and pathways of adaptive molecular evolution. In the genomes of at least some vertebrate taxa, an important form of mutation bias involves changes at CpG dinucleotides: if the DNA nucleotide cytosine (C) is immediately 5′ to guanine (G) on the same coding strand, then—depending on methylation status—point mutations at both sites occur at an elevated rate relative to mutations at non-CpG sites. Here, we examine experimental data from case studies in which it has been possible to identify the causative substitutions that are responsible for adaptive changes in the functional properties of vertebrate haemoglobin (Hb). Specifically, we examine the molecular basis of convergent increases in Hb–O 2 affinity in high-altitude birds. Using a dataset of experimentally verified, affinity-enhancing mutations in the Hbs of highland avian taxa, we tested whether causative changes are enriched for mutations at CpG dinucleotides relative to the frequency of CpG mutations among all possible missense mutations. The tests revealed that a disproportionate number of causative amino acid replacements were attributable to CpG mutations, suggesting that mutation bias can influence outcomes of molecular adaptation. This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.

Mutation bias can shape adaptation in large asexual populations experiencing clonal interference

“…The first two entries in Table 1 are expected to lie in the origin-fixation regime, albeit for different reasons. N is likely reasonably small for the natural bird popu-455 lations studied by Storz et al [16]. While N is much larger for the natural viral populations studied by Willis and Masel [40], the rate U of the beneficial de novo birth of new overlapping genes is likely so low that U N 1.…”

“…Studies of parallel adaptation in natural populations also reveal patterns suggestive of mutation bias, e.g. in sodium pump ATPα1 adaptations enabling 65 the consumption of glycosine toxins by insects [15], antibiotic resistance in Mycobacterium tuberculosis [9], and hemoglobin adaptations for high altitude in birds [16].…”

Mutation bias interacts with composition bias to influence adaptive evolution

“…Because mutation provides the raw material of evolution, mutation bias may influence adaptive evolutionary change [12][13][14]. Indeed, transition bias has influenced the adaptive evolution of phenotypes as different as antibiotic resistance in Mycobacterium tuberculosis [15] and increased hemoglobin-oxygen affinity in highaltitude birds [16].…”

The perils of intralocus recombination for inferences of molecular convergence

“…Whole-genome comparisons have revealed high levels of molecular convergence in multiple clades [7][8][9][10][11][12][13][14][15][16]. Although a large fraction of this convergence is undoubtedly due to non-adaptive processes [17][18][19], patterns of molecular convergence hold the promise of revealing general mechanisms of protein evolution [20,21].…”