Quantitative evolutionary dynamics using high-resolution lineage tracking

摘要

Evolution of large asexual cell populations underlies ～30% of deaths worldwide, including those caused by bacteria, fungi, parasites, and cancer. However, the dynamics underlying these evolutionary processes remain poorly understood because they involve many competing beneficial lineages, most of which never rise above extremely low frequencies in the population. To observe these normally hidden evolutionary dynamics, we constructed a sequencing-based ultra high-resolution lineage tracking system in Saccharomyces cerevisiae that allowed us to monitor the relative frequencies of ～500,000 lineages simultaneously. In contrast to some expectations, we found that the spectrum of fitness effects of beneficial mutations is neither exponential nor monotonic. Early adaptation is a predictable consequence of this spectrum and is strikingly reproducible, but the initial small-effect mutations are soon outcompeted by rarer large-effect mutations that result in variability between replicates. These results suggest that early evolutionary dynamics may be deterministic for a period of time before stochastic effects become important.%细菌、真菌、寄生虫和癌症等大型无性细胞群的演化动态仍不是很清楚，因为它们涉及很多竞争的世系。为了研究这些动态，Sasha Levy等人在酿酒酵母中建立了一个基于测序的超高分辨率世系追踪系统，并用它来同时监测大约50万个世系的相对频率。他们发现，虽然单一突变是随机出现的，但细胞群作为一个整体的早期动态却是群大小和突变速度对每个适应性效应(fitness effect)的分布的一个可预测的结果，而且具有非常强的可重现性。