Molecular specificity, convergence and constraint shape adaptive evolution in nutrient-poor environments.

Molecular specificity, convergence and constraint shape adaptive evolution in nutrient-poor environments.
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DOI:
10.1371/journal.pgen.1004041
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发表时间:
2014-01
期刊:
影响因子:
4.5
通讯作者:
Gresham D
Gresham D
中科院分区:
生物学2区
文献类型:
--
作者:
Hong J;Gresham D

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进化生物学的中心目标之一是解释和预测适应性进化的分子基础。我们研究了在不同氮限制条件下繁殖了 200 多代的酿酒酵母(芽殖酵母)群体的遗传网络进化。我们发现,贫氮环境中的快速适应性进化主要是拷贝数变异(CNV)的从头生成和选择,其中很大一部分包含编码特定氮转运蛋白(包括 PUT4、DUR3 和 DAL4)的基因。即使在具有多种氮源的环境中,与这些等位基因相关的适应性大幅增加也限制了适应群体的遗传异质性。对个体谱系和整个群体中获得性点突变的完整鉴定,确定了基因位点水平上的异质性,但功能模块水平上的共同主题,包括控制磷脂酰肌醇-3-磷酸代谢和液泡生物发生的基因。与其他营养有限环境共享的适应性策略表明,TORC1 和 Ras/PKA 信号通路中遗传变异的选择是营养有限环境中改善生长的一般机制。在单个群体中,我们观察到由功能相关基因 GAT1、MEP2 和 LST4 组成的多位点基因型的重复独立选择。通过研究个体等位基因的适应性及其组合,以及进化群体的进化历史,我们发现这些突变获得的顺序受到上位性的限制。功能相关基因座上重复选择的变异的识别表明,基因网络多态性(GNP)可能是适应性进化的常见结果。我们的结果提供了对细胞适应营养有限环境的机制基础的深入了解,并表明对选择性环境和对该环境中生长和生存很重要的调节机制的了解极大地增加了适应性进化的可预测性。我们通过在恒化器中长期选择无性繁殖的酿酒酵母种群,研究了不同氮限制环境中的适应性进化。利用下一代测序和 DNA 微阵列,我们在个体谱系和整个种群中鉴定出了与适应性增强相关的所有获得性遗传变异。我们发现,包括特定于环境中存在的氮分子形式的营养转运蛋白基因的扩增等位基因是增加适应性的常见机制。此外,我们还确定了适应氮限制环境的一般策略,该策略需要重塑产生重要细胞成分(包括液泡和自噬体)所需的磷脂生物发生。适应营养有限环境的更通用策略指出了信号通路重新布线的作用,以协调细胞生长与营养可用性。我们重建了在铵限制条件下进化的种群的进化动力学,发现多位点基因型在种群内被反复选择并受到上位性的限制。我们提出,这种基因型构成了“基因网络多态性(GNP)”,这可能是适应性进化的常见结果。我们的研究表明,当了解选择压力时,可以以合理的精度预测大型微生物种群适应性进化的分子基础。
One of the central goals of evolutionary biology is to explain and predict the molecular basis of adaptive evolution. We studied the evolution of genetic networks in Saccharomyces cerevisiae (budding yeast) populations propagated for more than 200 generations in different nitrogen-limiting conditions. We find that rapid adaptive evolution in nitrogen-poor environments is dominated by the de novo generation and selection of copy number variants (CNVs), a large fraction of which contain genes encoding specific nitrogen transporters including PUT4, DUR3 and DAL4. The large fitness increases associated with these alleles limits the genetic heterogeneity of adapting populations even in environments with multiple nitrogen sources. Complete identification of acquired point mutations, in individual lineages and entire populations, identified heterogeneity at the level of genetic loci but common themes at the level of functional modules, including genes controlling phosphatidylinositol-3-phosphate metabolism and vacuole biogenesis. Adaptive strategies shared with other nutrient-limited environments point to selection of genetic variation in the TORC1 and Ras/PKA signaling pathways as a general mechanism underlying improved growth in nutrient-limited environments. Within a single population we observed the repeated independent selection of a multi-locus genotype, comprised of the functionally related genes GAT1, MEP2 and LST4. By studying the fitness of individual alleles, and their combination, as well as the evolutionary history of the evolving population, we find that the order in which these mutations are acquired is constrained by epistasis. The identification of repeatedly selected variation at functionally related loci that interact epistatically suggests that gene network polymorphisms (GNPs) may be a frequent outcome of adaptive evolution. Our results provide insight into the mechanistic basis by which cells adapt to nutrient-limited environments and suggest that knowledge of the selective environment and the regulatory mechanisms important for growth and survival in that environment greatly increase the predictability of adaptive evolution. We studied adaptive evolution in different nitrogen-limited environments using long-term selection of asexually reproducing Saccharomyces cerevisiae populations in chemostats. Using next generation sequencing and DNA microarrays, we identified all acquired genetic variation associated with increased fitness, in both individual lineages and entire populations. We find that amplification alleles that include nutrient transporter genes specific to the molecular form of the nitrogen present in the environment are a common mechanism underlying increased fitness. In addition, we identified a general strategy for adaptation to nitrogen-limited environments that entails remodeling of phospholipid biogenesis required for producing important cellular components including vacuoles and autophagosomes. More general strategies for adaptation to nutrient-limited environments point to a role for re-wiring of signaling pathways that coordinate cell growth with nutrient availability. We reconstructed the evolutionary dynamics of a population evolving in ammonium-limited conditions and find that a multi-locus genotype is repeatedly selected within the population and constrained by epistasis. We propose that this genotype constitutes a “gene network polymorphism (GNP),” which may be a common outcome of adaptive evolution. Our study suggests that when the selective pressure is understood the molecular basis of adaptive evolution in large microbial populations may be predicted with reasonable precision.
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发表时间: 2007-01-01
期刊: NATURE PROTOCOLS
影响因子: 14.8
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期刊: YEAST
影响因子: 2.6
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