Experimental evolution and genome sequencing reveal variation in levels of clonal interference in large populations of bacteriophage φX174

Kim M Pepin,Holly A Wichman

doi:10.1186/1471-2148-8-85

Abstract

BackgroundIn large asexual populations where beneficial mutations may co-occur and recombination is absent, the fate of beneficial mutations can be significantly affected by competition (i.e., clonal interference). Theoretical models predict that clonal interference (CI) can slow adaptation, alter the distribution of fixed beneficial mutations, and affect disease progression by impacting within-host evolution of pathogens. While phenotypic data support that CI is a significant determinant of adaptive outcome, genetic data are needed to verify the patterns and to inform evolutionary models. We adapted replicate populations of the bacteriophage φX174 under two levels of CaCl2 to create benign and harsh environments. Genomic sequences of multiple individuals from evolved populations were used to detect competing beneficial mutations.ResultsThere were several competing genotypes in most of the populations where CaCl2 was abundant, but no evidence of CI where CaCl2 was scarce, even though rates of adaptation and population sizes among the treatments were similar. The sequence data revealed that observed mutations were limited to a single portion of one gene in the harsh treatment, but spanned a different and larger region of the genome under the benign treatments, suggesting that there were more adaptive solutions to the benign treatment.ConclusionBeneficial mutations with relatively large selection coefficients can be excluded by CI. CI may commonly determine the fate of beneficial mutations in large microbial populations, but its occurrence depends on selective conditions. CI was more frequent in benign selective conditions possibly due to a greater number of adaptive targets under this treatment. Additionally, the genomic sequence data showed that selection can target different types and numbers of phenotypes in environments that differ by only a single continuous variable.

Highlights

In large asexual populations where beneficial mutations may co-occur and recombination is absent, the fate of beneficial mutations can be significantly affected by competition
We verified with sequence data that clonal interference (CI) occurs in large virus populations and that several genotypes may cooccur at very high frequencies
While our data showed that CI was more frequent in benign treatments, this difference was not attributed to weaker selection

Summary

Introduction

In large asexual populations where beneficial mutations may co-occur and recombination is absent, the fate of beneficial mutations can be significantly affected by competition (i.e., clonal interference). Theoretical models predict that clonal interference (CI) can slow adaptation, alter the distribution of fixed beneficial mutations, and affect disease progression by impacting within-host evolution of pathogens. A less severe version of this type of interference, that can decrease the efficacy of selection in sexual organisms, occurs when a locus under weak selection is tightly linked to a more strongly selected locus (i.e., Hill-Robertson Effect; [5,6]) Both levels of interference can significantly impact adaptive outcome by decreasing the rate of adaptation, altering levels of standing genetic variation, and favoring the evolution of sex [3,7,8,9,10,11,12,13]. A better understanding of the effects of interference on the fate of beneficial mutations is important in advancing our knowledge of evolutionary processes; it has great practical relevance in monitoring and predicting disease progression in hosts with chronic infections [14]

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