High-resolution mapping of evolutionary trajectories in a phage

Dickins, B. ORCID: 0000-0002-0866-6232 and Nekrutenko, A., 2009. High-resolution mapping of evolutionary trajectories in a phage. Genome Biology and Evolution, 1, pp. 294-307. ISSN 1759-6653

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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 ɸX174. 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.

Item Type: Journal article
Publication Title: Genome Biology and Evolution
Creators: Dickins, B. and Nekrutenko, A.
Publisher: Oxford University Press
Place of Publication: Oxford
Date: 2009
Volume: 1
ISSN: 1759-6653
Divisions: Schools > School of Science and Technology
Record created by: EPrints Services
Date Added: 09 Oct 2015 10:52
Last Modified: 09 Jun 2017 13:43
URI: https://irep.ntu.ac.uk/id/eprint/19453

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