Genome-wide DNA divergence between O and B lines.

<p>The 95% quantiles of <i>t</i>-statistics within sliding windows of size 0.5Mb (by a sliding size of 0.1Mb) are plotted along the chromosome arms. The <i>t</i>-statistics are capped at 20 to enhance visualization of smaller differences.</p

The Genomic Basis of Postponed Senescence in <i>Drosophila melanogaster</i>

<div><p>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 <i>Drosophila melanogaster</i> 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 <i>X</i> 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 < 0.05) effects on gene expression with age, population and the age by population interaction, separately for each sex. We identified transcripts that exhibited the transcriptional signature of postponed senescence and integrated the gene expression and genetic divergence data to identify 98 (175) top candidate genes in females (males) affecting postponed senescence and increased lifespan. While several of these genes have been previously associated with <i>Drosophila</i> lifespan, most are novel and constitute a rich resource for future functional validation.</p></div

Numbers of significant (FDR < 0.05) annotated genes for each term in the ANOVA models of gene expression.

<p>W1: Week 1; W5: Week 5.</p><p>* These numbers do not sum to the total numbers in both sexes because of differences in the directionality of effects across sexes.</p><p>3,085 genes have a significant age effect in both the male and female dataset but only 2660 have an effect in the same direction. The remaining 425 genes are up-regulated in one sex and down-regulated in the other. Likewise, 5 genes have opposite effects in the B and O populations.</p><p>Numbers of significant (FDR < 0.05) annotated genes for each term in the ANOVA models of gene expression.</p