The Genomic Basis of Postponed Senescence in Drosophila melanogaster

Natural populations harbor considerable genetic variation for lifespan. While evolutionary theory provides general explanations for the existence of this variation, our knowledge of the genes harboring naturally occurring polymorphisms affecting lifespan is limited. Here, we assessed the genetic divergence between five Drosophila melanogaster lines selected for postponed senescence for over 170 generations (O lines) and five lines from the same base population maintained at a two week generation interval for over 850 generations (B lines). On average, O lines live 70% longer than B lines, are more productive at all ages, and have delayed senescence for other traits than reproduction. We performed population sequencing of pools of individuals from all B and O lines and identified 6,394 genetically divergent variants in or near 1,928 genes at a false discovery rate of 0.068. A 2.6 Mb region at the tip of the X chromosome contained many variants fixed for alternative alleles in the two populations, suggestive of a hard selective sweep. We also assessed genome wide gene expression of O and B lines at one and five weeks of age using RNA sequencing and identified genes with significant (false discovery rate Drosophila lifespan, most are novel and constitute a rich resource for future functional validation.

自然种群中蕴藏着大量与寿命相关的遗传变异。尽管演化理论已对这类变异的存在给出了一般性解释，但我们对携带影响寿命的自然多态性的基因仍所知有限。本研究针对170余代持续选育以延缓衰老的5个黑腹果蝇（Drosophila melanogaster）品系（O品系），以及来自同一基础种群、以两周为繁殖间隔传代850余代的5个对照品系（B品系）之间的遗传分化展开分析。平均而言，O品系的寿命较B品系延长70%，各年龄段的繁殖能力更强，且除繁殖性状外的其他衰老相关表型也出现延缓。我们对所有B、O品系的混合个体开展群体测序，在1928个基因及其侧翼区域中鉴定出6394个遗传分化变异，假发现率（false discovery rate）为0.068。X染色体末端的2.6 Mb区域存在大量在两个种群中固定为不同等位基因的变异，提示发生了一次硬选择性清扫（hard selective sweep）。我们还利用RNA测序（RNA sequencing）技术，对1周龄和5周龄的O、B品系进行全基因组基因表达分析，鉴定出与黑腹果蝇寿命相关的显著差异表达基因（原文此处假发现率标注存在缺失）；其中绝大多数为新发现的基因，可为后续功能验证提供丰富的研究资源。