Mutation-Driven Parallel Evolution during Viral Adaptation

Abstract

Convergent evolution has been demonstrated across all levels of biological organization, from parallel nucleotide substitutions to convergent evolution of complex phenotypes, but whether instances of convergence are the result of selection repeatedly finding the same optimal solution to a recurring problem or are the product of mutational biases remains unsettled. We generated 20 replicate lineages allowed to fix a single mutation from each of four bacteriophage genotypes under identical selective regimes to test for parallel changes within and across genotypes at the levels of mutational effect distributions and gene, protein, amino acid, and nucleotide changes. All four genotypes shared a distribution of beneficial mutational effects best approximated by a distribution with a finite upper bound. Parallel adaptation was high at the protein, gene, amino acid, and nucleotide levels, both within and among phage genotypes, with the most common first-step mutation in each background fixing on an average in 7 of 20 replicates and half of the substitutions in two of the four genotypes occurring at shared sites. Remarkably, the mutation of largest beneficial effect that fixed for each genotype was never the most common, as would be expected if parallelism were driven by selection. In fact, the mutation of smallest benefit for each genotype fixed in a total of 7 of 80 lineages, equally as often as the mutation of largest benefit, leading us to conclude that adaptation was largely mutation-driven, such that mutational biases led to frequent parallel fixation of mutations of suboptimal effect.

Gene Birth Contributes to Structural Disorder Encoded by Overlapping Genes

“…This means that differences in the beneficial mutation rate are just as important as differences in the selection coefficient in determining which path adaptive evolution takes (Yampolsky and Stoltzfus 2001). The influence of mutational bias has previously been observed for beneficial mutations to single amino acids in the laboratory McCandlish 2015, 2017;Sackman et al 2017) and in the wild (Stoltzfus and McCandlish 2017;Zhu et al 2018). Here, we demonstrate it for more radical mutations, namely the de novo birth of entire protein-coding genes.…”

The phylogenomics of evolving virus virulence

“…The greater the fitness of a virulence determinant, the more rapidly it will spread through the virus population and the deeper it will fall on a virus phylogeny (that is, closer to the root of the tree), including on the branch linking reservoir and novel hosts. Of particular importance are repeated occurrences of the same mutation falling on deep branches across multiple outbreaks, or multiple cross-species transmission events, as both parallel evolution and convergent evolution can be signatures of adaptive evolution 8,[54][55][56][57] (FIg. 1).…”

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

“…Note that many but not all of these argue on the basis 445 of transition : transversion ratio [15,9,12,39]. According to a selection-driven model, in which each mutation is equally likely to be beneficial, adaptive point mutations should have a 1 transition : 2 transversion ratio.…”

“…This phenomenon now has substantial empirical support [10]. Evidence for adaptation aligned with mutation bias has been found during 60 the experimental evolution of microvirid bacteriophage [11,12], Escherichia coli [13], and Pseudomonas aeruginosa [14,15]. Studies of parallel adaptation in natural populations also reveal patterns suggestive of mutation bias, e.g.…”

“…For this reason, previous theoretical arguments in favor of mutation-biased adaptation have been restricted to the parameter regime U N log(N s) 1, and the phenomenon has been criticized on this basis [3]. However, clonal interference may occur in at least some of empir-100 ically documented cases of mutation-biased adaptation [14, 21,12]. There is therefore a need for theory to understand how mutation-biased adaptation might be possible in the presence of clonal interference.…”