Department of Physics, Harvard University, Cambridge, MA 02138;
Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138.
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11448-11453. doi: 10.1073/pnas.1809587115. Epub 2018 Oct 23.
Microbial populations often assemble in dense populations in which proliferating individuals exert mechanical forces on the nearby cells. Here, we use yeast strains whose doubling times depend differently on temperature to show that physical interactions among cells affect the competition between different genotypes in growing yeast colonies. Our experiments demonstrate that these physical interactions have two related effects: they cause the prolonged survival of slower-growing strains at the actively-growing frontier of the colony and cause faster-growing strains to increase their frequency more slowly than expected in the absence of physical interactions. These effects also promote the survival of slower-growing strains and the maintenance of genetic diversity in colonies grown in time-varying environments. A continuum model inspired by overdamped hydrodynamics reproduces the experiments and predicts that the strength of natural selection depends on the width of the actively growing layer at the colony frontier. We verify these predictions experimentally. The reduced power of natural selection observed here may favor the maintenance of drug-resistant cells in microbial populations and could explain the apparent neutrality of interclone competition within tumors.
微生物种群通常在密集的种群中聚集,在这些种群中,增殖的个体对附近的细胞施加机械力。在这里,我们使用酵母菌株,其倍增时间随温度的变化而不同,以表明细胞之间的物理相互作用会影响生长中的酵母菌落中不同基因型之间的竞争。我们的实验表明,这些物理相互作用有两个相关的影响:它们导致在菌落的活跃生长前沿,生长较慢的菌株的存活时间延长,并且导致生长较快的菌株在没有物理相互作用的情况下,其频率增加的速度比预期的慢。这些效应还促进了生长较慢的菌株的存活和在时变环境中生长的菌落中遗传多样性的维持。受过阻尼流体动力学启发的连续统模型再现了实验,并预测自然选择的强度取决于菌落前沿活跃生长层的宽度。我们通过实验验证了这些预测。这里观察到的自然选择能力的降低可能有利于微生物种群中耐药细胞的维持,并可以解释肿瘤内克隆间竞争的明显中性。