Genome-Wide Analysis of Starvation-Selected Drosophila melanogaster-A Genetic Model of Obesity
Genome-Wide Analysis of Starvation-Selected Drosophila melanogaster-A Genetic Model of Obesity
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DOI：
10.1093/molbev/msx254
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发表时间：
2018-01-01
影响因子：
10.7
通讯作者：
Gibbs, Allen G.
中科院分区：
文献类型：
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作者：
Hardy, Christopher M.;Burke, Molly K.;Gibbs, Allen G.
实验进化为研究对压力环境的适应提供了机会。将实验进化与全基因组重测序相结合的研究提供了对适应动力学的深入了解，并为揭示与多基因性状相关的基因提供了新的工具。在这里，我们选择了超过80代的黑腹果蝇种群的饥饿抗性。作为回应，饥饿选择的品系出现了肥胖状况，它们储存的总脂质水平几乎是未选择的对照组的两倍。尽管这些脂肪提供了3倍的饥饿抵抗能力，但脂质稳态的不平衡导致了进化代价。其中一些权衡类似于哺乳动物的肥胖相关病理，包括代谢抑制、低活动水平、扩张性心肌病和睡眠模式中断。为了确定这些性状的遗传基础，我们对所选品系及其对照的基因组DNA进行了重新测序。我们发现了1,046,373个多态性位点，其中许多位点在不同的选择处理之间出现了分化。此外，我们发现所选系的重复之间存在广泛的遗传异质性，表明存在多种适应机制。在选择的种群中，全基因组杂合性较低，许多大片段的snp接近固定。我们使用一种算法来控制遗传漂变的影响，在选择下找到候选位点。这些基因座被定位到一组382个基因，这些基因与许多过程相关，包括营养反应、分解代谢和脂滴功能。我们的研究结果说明了肥胖的进化起源，并在一个独特的模型系统中为理解肥胖的多基因性质提供了新的目标。
Experimental evolution affords the opportunity to investigate adaptation to stressful environments. Studies combining experimental evolution with whole-genome resequencing have provided insight into the dynamics of adaptation and a new tool to uncover genes associated with polygenic traits. Here, we selected for starvation resistance in populations of Drosophila melanogaster for over 80 generations. In response, the starvation-selected lines developed an obese condition, storing nearly twice the level of total lipids than their unselected controls. Although these fats provide a similar to 3-fold increase in starvation resistance, the imbalance in lipid homeostasis incurs evolutionary cost. Some of these tradeoffs resemble obesity-associated pathologies in mammals including metabolic depression, low activity levels, dilated cardiomyopathy, and disrupted sleeping patterns. To determine the genetic basis of these traits, we resequenced genomic DNA from the selected lines and their controls. We found 1,046,373 polymorphic sites, many of which diverged between selection treatments. In addition, we found a wide range of genetic heterogeneity between the replicates of the selected lines, suggesting multiple mechanisms of adaptation. Genome-wide heterozygosity was low in the selected populations, with many large blocks of SNPs nearing fixation. We found candidate loci under selection by using an algorithm to control for the effects of genetic drift. These loci were mapped to a set of 382 genes, which associated with many processes including nutrient response, catabolic metabolism, and lipid droplet function. The results of our study speak to the evolutionary origins of obesity and provide new targets to understand the polygenic nature of obesity in a unique model system.