Quantifying bacterial evolution in the wild: a birthday problem for Campylobacter lineages

Measuring molecular evolution in
bacteria typically requires estimation of the rate at which mutations
accumulate in strains sampled at different times that share a common ancestor. This
approach has been useful for dating ecological and evolutionary events that
coincide with the emergence of important lineages, such as outbreak strains and
obligate human pathogens. However, in multi-host (niche) transmission
scenarios, where the pathogen is essentially an opportunistic environmental
organism, sampling is often sporadic and rarely reflects the overall
population, particularly when concentrated on clinical isolates. This means
that approaches that assume recent common ancestry are not applicable. Here we
present a new approach to estimate the molecular clock rate in Campylobacter
that draws on the popular probability conundrum known as the ‘birthday
problem’. Using large genomic datasets and comparative genomic approaches, we
identify isolate pairs where common ancestry is inferred within the sample
time-frame – analogous to a shared birthday. Identifying synonymous and
non-synonymous substitutions, both within and outside of recombinant regions of
the genome, we quantify clock-like diversification to estimate mutation rates
for the common pathogenic species Campylobacter coli (2.4 x 10-6
s/s/y) and Campylobacter jejuni (3.4
x 10-6 s/s/y). Finally, using estimated mutation rates we assess the
rate of turnover of lineages in our sample set over short evolutionary
timescales. This provides a generalisable approach to calibrating mutation
rates in populations of environmental bacteria and shows that multiple lineages
are maintained, implying that large-scale clonal sweeps may take hundreds of
years or more in these species.