The Adaptive Significance of Natural Genetic Variation in the DNA Damage Response of Drosophila melanogaster.
The Adaptive Significance of Natural Genetic Variation in the DNA Damage Response of Drosophila melanogaster.
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DOI：
10.1371/journal.pgen.1005869
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发表时间：
2016-03
期刊：
影响因子：
4.5
通讯作者：
Begun DJ
中科院分区：
文献类型：
--
作者：
Svetec N;Cridland JM;Zhao L;Begun DJ
尽管经过了几十年的工作，我们对自然种群中分离遗传变异的适应性效应分布的理解仍然很不完整。可以维持遗传变异的一种选择形式是空间变化选择，例如导致纬度倾斜的选择。虽然引入群体基因组学方法来理解空间变化的选择已经引起了很大的兴奋，但很少有成功的努力致力于从基因组扫描选择到相关生物学的实验分析和关于选择因素的实验动机假设的发展;关于绝大多数人口基因组工作是否会导致令人满意的生物学见解，这仍然是一个有趣的问题。在这里，人口基因组结果的动机，我们调查如何在空间上不同的选择在遗传模型系统，果蝇，导致了遗传差异的几个组成部分的DNA损伤反应的人口。UVB辐射率与纬度呈负相关，是DNA损伤的重要因素。我们发现早期胚胎对UVB照射的敏感性与纬度密切相关，低纬度人群对UVB的敏感性要低得多。然后，我们表明，具有较低胚胎UVB敏感性的品系也表现出卵母细胞修复受损精子DNA的能力增加。高纬度和低纬度胚胎的早期胚胎转录组的比较提供了证据，表明种群之间适应性DNA修复差异的一种机制是低纬度雌性卵子中DNA修复转录本的丰度更高。最后，我们使用高纬度和低纬度样本的人口基因组比较，揭示证据表明，DNA损伤反应的多个组成部分和编码和非编码变异可能有助于适应性差异的DNA修复种群之间。了解遗传和表型多样性是如何在自然种群中产生和维持的是生物学的一个中心问题。D.黑腹果蝇是研究当地适应的生物学和种群遗传学基础的模型系统。群体基因组学领域最近的技术和统计进展为研究空间变化选择所维持的自然分离变异的程度和性质开辟了新的机会。在这里，我们测试的假设产生的人口基因组方法表明，DNA修复的影响，空间变化的选择在D。黑腹菌我们假设，UVB，这会导致DNA损伤，并随纬度而变化，可能与基因组复制应力在早期胚胎发生，导致空间变化的选择在这个物种的DNA修复。在这里，我们结合联合收割机表型，遗传，转录组学和人口基因组分析支持这一假设。
Despite decades of work, our understanding of the distribution of fitness effects of segregating genetic variants in natural populations remains largely incomplete. One form of selection that can maintain genetic variation is spatially varying selection, such as that leading to latitudinal clines. While the introduction of population genomic approaches to understanding spatially varying selection has generated much excitement, little successful effort has been devoted to moving beyond genome scans for selection to experimental analysis of the relevant biology and the development of experimentally motivated hypotheses regarding the agents of selection; it remains an interesting question as to whether the vast majority of population genomic work will lead to satisfying biological insights. Here, motivated by population genomic results, we investigate how spatially varying selection in the genetic model system, Drosophila melanogaster, has led to genetic differences between populations in several components of the DNA damage response. UVB incidence, which is negatively correlated with latitude, is an important agent of DNA damage. We show that sensitivity of early embryos to UVB exposure is strongly correlated with latitude such that low latitude populations show much lower sensitivity to UVB. We then show that lines with lower embryo UVB sensitivity also exhibit increased capacity for repair of damaged sperm DNA by the oocyte. A comparison of the early embryo transcriptome in high and low latitude embryos provides evidence that one mechanism of adaptive DNA repair differences between populations is the greater abundance of DNA repair transcripts in the eggs of low latitude females. Finally, we use population genomic comparisons of high and low latitude samples to reveal evidence that multiple components of the DNA damage response and both coding and non-coding variation likely contribute to adaptive differences in DNA repair between populations. Understanding how genetic and phenotypic diversity are generated and maintained in natural populations is a central question in biology. Latitudinal clines in D. melanogaster represent a model system for investigating the biological and population genetic basis for local adaptation. Recent technological and statistical advances in population genomics have opened up new opportunities for investigating the extent and nature of naturally segregating variation maintained by spatially varying selection. Here, we test hypotheses generated from population genomic approaches suggesting that DNA repair is influenced by spatially varying selection in D. melanogaster. We hypothesized that UVB, which causes DNA damage and varies with latitude, could interact with genome replication stress during early embryogenesis, leading to spatially varying selection on DNA repair in this species. Here, we combine phenotypic, genetic, transcriptomic, and population genomic analyses supporting this hypothesis.