Abstract
The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution.
Highlights
IntroductionThe dynamics of adaptive evolution are more intricate than a simple sum of mutation and selection due to the entanglement of several evolutionary events [1], which include rare adaptive mutations [2,3,4,5,6,7,8], epistasis [9,10,11] and hitchhiking [12,13,14] at the genome level and clonal interference [15], frequency-dependent selection [16] and genetic drift [17] at the population level
The fixation of neutral mutations in populations has been attributed to genetic drift in fitness-steady evolutionary processes or hitchhiking in adaptive evolution
We examined the fitness-increasing evolution of Escherichia coli for thermal adaptation to observe the fixation dynamics of genome-wide mutations
Summary
The dynamics of adaptive evolution are more intricate than a simple sum of mutation and selection due to the entanglement of several evolutionary events [1], which include rare adaptive mutations [2,3,4,5,6,7,8], epistasis [9,10,11] and hitchhiking [12,13,14] at the genome level and clonal interference [15], frequency-dependent selection [16] and genetic drift [17] at the population level. Recent genomic sequencing analyses of yeast evolution experiment have confirmed that the rise and fall of adaptive genotypes are complicated due to the concurrence of hitchhiking and clonal interference [14]. Despite these recently uncovered complicated dynamics, a constant mutation fixation rate in a population is considered a simple rule in phylogenetic analysis. The constancy of the mutation fixation rate may vary to some extent, the molecular clock has become a simple tool for evolutionary researchers to convert mutational differences into phylogenetic trees to trace past evolutionary events [19,22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
