Excess of mutational jackpot events in expanding populations revealed by spatial Luria-Delbrück experiments.
Excess of mutational jackpot events in expanding populations revealed by spatial Luria-Delbrück experiments.
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DOI：
10.1038/ncomms12760
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发表时间：
2016-10-03
影响因子：
16.6
通讯作者：
Hallatschek O
中科院分区：
文献类型：
--
作者：
Fusco D;Gralka M;Kayser J;Anderson A;Hallatschek O
生长中的细胞群体（例如生物膜、实体瘤或发育中的胚胎）的遗传多样性被认为是由罕见的、异常大的突变克隆主导的。然而，这些突变大奖事件的出现只有在混合良好的群体中才能被理解，它们源于最初几次细胞分裂期间出现的突变。为了研究空间结构群体中的头奖事件，我们使用荧光显微镜和群体测序来追踪微生物群体中的突变克隆。人们发现，与充分摇匀的液体培养物相比，微生物菌落中的高频突变大量富集，这是由于晚期发生的突变在范围扩展的边缘冲浪的结果。因此，不仅当突变早期出现时，而且当突变发生在有利的位置时，也会产生大奖事件，这加剧了它们在适应和疾病中的作用。特别是，由于与野生型的空间竞争使大多数突变克隆处于静止状态，杀死野生型的强大选择压力会促进耐药性。 生长中的细胞群中早期突变产生的大型突变克隆促进微生物和肿瘤的短期进化。在这里，作者分析了空间扩张的菌落，并表明，当它们在扩张的前沿冲浪时，大型突变克隆也可能出现较晚。
The genetic diversity of growing cellular populations, such as biofilms, solid tumours or developing embryos, is thought to be dominated by rare, exceptionally large mutant clones. Yet, the emergence of these mutational jackpot events is only understood in well-mixed populations, where they stem from mutations that arise during the first few cell divisions. To study jackpot events in spatially structured populations, we track mutant clones in microbial populations using fluorescence microscopy and population sequencing. High-frequency mutations are found to be massively enriched in microbial colonies compared with well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. Thus, jackpot events can be generated not only when mutations arise early but also when they occur at favourable locations, which exacerbates their role in adaptation and disease. In particular, because spatial competition with the wild type keeps most mutant clones in a quiescent state, strong selection pressures that kill the wild type promote drug resistance. Large mutant clones arising from early mutations in growing cell populations facilitate short-term evolution in microbes and in tumours. Here the authors analyse spatially expanding colonies, and show that large mutant clones can also arise late when they surf at expanding frontiers.
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影响因子：
17.1
作者：
Enriquez-Navas PM;Kam Y;Das T;Hassan S;Silva A;Foroutan P;Ruiz E;Martinez G;Minton S;Gillies RJ;Gatenby RA
通讯作者：
Gatenby RA
影响因子：
8.6
作者：
KARDAR, M;PARISI, G;ZHANG, YC
通讯作者：
ZHANG, YC
影响因子：
3.3
作者：
Haeno, Hiroshi;Iwasa, Yoh;Michor, Franziska
通讯作者：
Michor, Franziska
影响因子：
64.8
作者：
Frank, SA;Nowak, MA
通讯作者：
Nowak, MA
影响因子：
1.4
作者：
Lavrentovich, Maxim O.;Nelson, David R.
通讯作者：
Nelson, David R.