Horizontal gene transfer may explain variation in {\theta}s

TL;DR

This study investigates the causes of variation in synonymous diversity ({ heta}s) among E. coli genes, finding that horizontal gene transfer (HGT) history, rather than mutation rate differences, explains the observed patterns.

Contribution

It demonstrates that HGT events, not mutation rate variation, primarily account for { heta}s differences across genes in E. coli genomes.

Findings

No significant variation in synonymous substitution rates among genes.

{ heta}s correlates with HGT events, not mutation rates.

HGT history explains { heta}s variation better than mutation rate differences.

Abstract

Martincorena et al. estimated synonymous diversity ({\theta}s = 2N{\mu}) across 2,930 orthologous gene alignments from 34 Escherichia coli genomes, and found substantial variation among genes in the density of synonymous polymorphisms. They argue that this pattern reflects variation in the mutation rate per nucleotide ({\mu}) among genes. However, the effective population size (N) is not necessarily constant across the genome. In particular, different genes may have different histories of horizontal gene transfer (HGT), whereas Martincorena et al. used a model with random recombination to calculate {\theta}s. They did filter alignments in an effort to minimize the effects of HGT, but we doubt that any procedure can completely eliminate HGT among closely related genomes, such as E. coli living in the complex gut community. Here we show that there is no significant variation among genes in rates of synonymous substitutions in a long-term evolution experiment with E. coli and that the per-gene rates are not correlated with {\theta}s estimates from genome comparisons. However, there is a significant association between {\theta}s and HGT events. Together, these findings imply that {\theta}s variation reflects different histories of HGT, not local optimization of mutation rates to reduce the risk of deleterious mutations as proposed by Martincorena et al.