Impact of crowding on the diversity of expanding populations.
Impact of crowding on the diversity of expanding populations.
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拥挤对扩大人口多样性的影响。
DOI：
10.1073/pnas.2208361120
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发表时间：
2023-03-14
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
随着细胞的增殖和填充空间，生长的细胞群变得密集。拥挤阻止了个体的空间混合，极大地改变了混合良好的种群的进化结果。尽管空间种群和混合种群之间存在根本差异，但人们对拥挤对遗传多样性的影响知之甚少。对于平板上的微生物菌落，我们表明等位基因频谱在低频时具有幂律特征。利用基于细胞的模拟和微流体实验，我们在拥挤的细胞环境中确定了这种分布在体积排斥相互作用中的起源，使我们能够将这些发现扩展到广泛的密集人群。这项研究强调了细胞拥挤对罕见遗传变异出现的重要性。拥挤效应严重影响密集排列的细胞组合的自组织，如生物膜、实体肿瘤和发育中的组织。当细胞生长和分裂时，它们相互推开，重塑了种群的结构和范围。最近的研究表明，拥挤对自然选择的强度有很强的影响。然而，拥挤对中性过程的影响仍然不清楚，中性过程控制着新变异的命运，只要它们是罕见的。在这里，我们量化了扩大微生物菌落的遗传多样性，并揭示了站点频谱中拥挤的特征。通过结合luria - delbr<e:1> ck波动测试、新型微流体培养箱中的谱系追踪、基于细胞的模拟和理论建模，我们发现大多数突变发生在扩展的边界后面，导致克隆被前面增殖的细胞机械地“推出”生长区域。这些排除体积的相互作用导致克隆大小分布完全取决于相对于前面的突变首次出现的位置，并且以低频克隆的简单幂律为特征。我们的模型预测，这种分布取决于一个单一的参数——特征生长层厚度——因此可以估计各种拥挤的细胞群体中的突变率。结合以往对高频突变的研究，我们的发现提供了在整个频率范围内扩展种群的遗传多样性的统一图景，并提出了一种通过跨空间尺度的种群测序来评估生长动态的实用方法。
Growing cell populations become densely packed as cells proliferate and fill space. Crowding prevents spatial mixing of individuals, significantly altering the evolutionary outcome from established results for well-mixed populations. Despite the fundamental differences between spatial and well-mixed populations, little is known about the impact of crowding on genetic diversity. With microbial colonies on plates, we show that the allele frequency spectrum is characterized by a power law for low frequencies. Using cell-based simulations and microfluidic experiments, we identify the origin of this distribution in the volume-exclusion interactions within the crowded cellular environment, enabling us to extend these findings to a broad range of dense populations. This study highlights the importance of cellular crowding for the emergence of rare genetic variants. Crowding effects critically impact the self-organization of densely packed cellular assemblies, such as biofilms, solid tumors, and developing tissues. When cells grow and divide, they push each other apart, remodeling the structure and extent of the population’s range. Recent work has shown that crowding has a strong impact on the strength of natural selection. However, the impact of crowding on neutral processes, which controls the fate of new variants as long as they are rare, remains unclear. Here, we quantify the genetic diversity of expanding microbial colonies and uncover signatures of crowding in the site frequency spectrum. By combining Luria–Delbrück fluctuation tests, lineage tracing in a novel microfluidic incubator, cell-based simulations, and theoretical modeling, we find that the majority of mutations arise behind the expanding frontier, giving rise to clones that are mechanically “pushed out” of the growing region by the proliferating cells in front. These excluded-volume interactions result in a clone-size distribution that solely depends on where the mutation first arose relative to the front and is characterized by a simple power law for low-frequency clones. Our model predicts that the distribution depends on a single parameter—the characteristic growth layer thickness—and hence allows estimation of the mutation rate in a variety of crowded cellular populations. Combined with previous studies on high-frequency mutations, our finding provides a unified picture of the genetic diversity in expanding populations over the whole frequency range and suggests a practical method to assess growth dynamics by sequencing populations across spatial scales.
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影响因子：
19.6
作者：
通讯作者：
--
DOI：
10.1038/nrmicro3552
发表时间：
2016-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Donaldson GP;Lee SM;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
4.5
作者：
Lambert G;Kussell E
通讯作者：
Kussell E
DOI：
10.1073/pnas.37.3.146
发表时间：
1951-01-01
影响因子：
11.1
作者：
ATWOOD, KC;SCHNEIDER, LK;RYAN, FJ
通讯作者：
RYAN, FJ
DOI：
10.1073/pnas.0710150104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Hallatschek, Oskar;Hersen, Pascal;Nelson, David R.
通讯作者：
Nelson, David R.