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Estimating the distribution of selection coefficients from phylogenetic data using sitewise mutation-selection

Asif U Tamuri¹, Mario dos Reis, Richard A Goldstein

¹Medical Research Council National Institute for Medical Research, London, NW7 1AA, United Kingdom.

|January 3, 2012

Summary

This study reveals a bimodal distribution for novel mutations in mammalian mitochondrial and influenza proteins, indicating most are deleterious. Substitutions, however, show a unimodal distribution, suggesting evolutionary adaptation.

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Area of Science:

Molecular Evolution
Phylogenetics
Population Genetics

Background:

Estimating selection coefficient distributions is crucial in molecular evolution.
Previous phylogenetic models often suggested unimodal distributions for mutations.
Novel and fixed mutations (substitutions) require distinct analytical approaches.

Purpose of the Study:

To estimate selection coefficient distributions for novel and fixed mutations using a phylogenetic model.
To analyze mammalian mitochondrial genomes and influenza PB2 proteins.
To investigate the impact of host shifts on mutation selection coefficients.

Main Methods:

Employed a sitewise mutation-selection phylogenetic model.
Analyzed 244 mammalian mitochondrial genomes.
Analyzed 401 PB2 protein sequences from influenza.

Main Results:

A bimodal distribution of selection coefficients was found for novel mutations in both datasets.
Most novel mutations were strongly deleterious, with a smaller proportion being mildly deleterious to neutral.
Substitutions showed a unimodal, near-neutral distribution at adaptive equilibrium.
Advantageous mutations constituted ~0.5% of nonsynonymous mutations and 14% of substitutions in mitochondrial proteins.
Advantageous mutations constituted ~0.5% of nonsynonymous mutations and 24% of substitutions in influenza proteins.
Influenza PB2 novel mutations exhibited a trimodal distribution after a host shift to humans, including advantageous mutations.

Conclusions:

Novel mutations are predominantly deleterious, while substitutions tend towards neutrality.
Influenza evolution shows a significant proportion of advantageous mutations, especially after host shifts.
The study provides a more nuanced view of selection pressures acting on molecular evolution.