Abstract

Evolution of RNA bacteriophages of the family Leviviridae is governed by the high error rates of their RNA-dependent RNA polymerases. This fact, together with their large population sizes, leads to the generation of highly heterogeneous populations that adapt rapidly to most changes in the environment. Throughout adaptation, the different mutants that make up a viral population compete with each other in a non-trivial process in which their selective values change over time due to the generation of new mutations. In this work we have characterised the intra-population dynamics of a well-studied levivirus, Qβ, when it is propagated at a higher-than-optimal temperature. Our results show that adapting populations experienced rapid changes that involved the ascent of particular genotypes and the loss of some beneficial mutations of early generation. Artificially reconstructed populations, containing a fraction of the diversity present in actual populations, fixed mutations more rapidly, illustrating how population bottlenecks may guide the adaptive pathways. The conclusion is that, when the availability of beneficial mutations under a particular selective condition is elevated, the final outcome of adaptation depends more on the occasional occurrence of population bottlenecks and how mutations combine in genomes than on the selective value of particular mutations.

Highlights

  • Whereas the most relevant feature of DNA phage evolution is genetic mosaicism resulting from recombination between non-identical ancestors [1], RNA phage evolution of the family Leviviridae is governed by the high error rate of their RNA-dependent RNA polymerases (RdRp), in the order of 10−4 to 10−6 errors per nucleotide copied [2,3,4]

  • In this work we studied the process of internal competition among mutants that takes place during RNA bacteriophage adaptation, using Qβ as an experimental system and the increase in the replication temperature as the selective pressure

  • The two evolutionary lineages analysed showed a clear increase in their growth rate at 43 ◦ C after 25 transfers at this temperature, which is indicative of adaptation

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Summary

Introduction

Whereas the most relevant feature of DNA phage evolution is genetic mosaicism resulting from recombination between non-identical ancestors [1], RNA phage evolution of the family Leviviridae is governed by the high error rate of their RNA-dependent RNA polymerases (RdRp), in the order of 10−4 to 10−6 errors per nucleotide copied [2,3,4] As it happens in other RNA viruses, this fact, together with their short generation times and usually large population sizes, gives rise to highly heterogeneous populations, referred to as quasispecies [5,6,7], which are composed of a dynamic mutant spectrum that is responsible for a large part of their properties. This coexistence of mutants may have unexpected consequences, as we will detail below

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