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Title: Estimates of the Effect of Natural Selection on Protein-Coding Content
Authors: Yap, V.B. 
Lindsay, H.
Easteal, S.
Huttley, G.
Keywords: Codon substitution models
Maximum likelihood
Molecular evolution
Natural selection
Issue Date: Mar-2010
Citation: Yap, V.B., Lindsay, H., Easteal, S., Huttley, G. (2010-03). Estimates of the Effect of Natural Selection on Protein-Coding Content. Molecular Biology and Evolution 27 (3) : 726-734. ScholarBank@NUS Repository.
Abstract: Analysis of natural selection is key to understanding many core biological processes, including the emergence of competition, cooperation, and complexity, and has important applications in the targeted development of vaccines. Selection is hard to observe directly but can be inferred from molecular sequence variation. For protein-coding nucleotide sequences, the ratio of nonsynonymous to synonymous substitutions (ω) distinguishes neutrally evolving sequences (ω = 1) from those subjected to purifying (ω < 1) or positive Darwinian (ω > 1) selection. We show that current models used to estimate ω are substantially biased by naturally occurring sequence compositions. We present a novel model that weights substitutions by conditional nucleotide frequencies and which escapes these artifacts. Applying it to the genomes of pathogens causing malaria, leprosy, tuberculosis, and Lyme disease gave significant discrepancies in estimates with ∼10-30% of genes affected. Our work has substantial implications for how vaccine targets are chosen and for studying the molecular basis of adaptive evolution.
Source Title: Molecular Biology and Evolution
ISSN: 07374038
DOI: 10.1093/molbev/msp232
Appears in Collections:Staff Publications

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