Journal Article

High-Resolution Mapping of Evolutionary Trajectories in a Phage

Benjamin Dickins and Anton Nekrutenko

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 1, issue , pages 294-307
Published in print January 2009 |
Published online August 2009 | e-ISSN: 1759-6653 | DOI:

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  • Bioinformatics and Computational Biology
  • Evolutionary Biology
  • Genetics and Genomics


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Experimental evolution in rapidly reproducing viruses offers a robust means to infer substitution trajectories during evolution. But with conventional approaches, this inference is limited by how many individual genotypes can be sampled from the population at a time. Low-frequency changes are difficult to detect, potentially rendering early stages of adaptation unobservable. Here we circumvent this using short-read sequencing technology in a fine-grained analysis of polymorphism dynamics in the sentinel organism: a single-stranded DNA phage ΦX174. Nucleotide differences were educed from noise with binomial filtering methods that harnessed quality scores and separate data from brief phage amplifications. Remarkably, a significant degree of variation was observed in all samples including those grown in brief 2-h cultures. Sites previously reported as subject to high-frequency polymorphisms over a course of weeks exhibited monotonic increases in polymorphism frequency within hours in this study. Additionally, even with limitations imposed by the short length of sequencing reads, we were able to observe statistically significant linkage among polymorphic sites in evolved lineages. Additional parallels between replicate lineages were apparent in the sharing of polymorphic sites and in correlated polymorphism frequencies. Missense mutations were more likely to occur than silent mutations. This study offers the first glimpse into “real-time” substitution dynamics and offers a robust conceptual framework for future viral resequencing studies.

Keywords: experimental evolution; next-generation sequencing; substitution analysis

Journal Article.  7699 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

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