Dietary stress remodels the genetic architecture of lifespan variation in outbred Drosophila

Luisa F. Pallares, Amanda J. Lea, Clair Han, Elena V. Filippova, Peter Andolfatto, Julien F. Ayroles

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Evolutionary theory suggests that lifespan-reducing alleles should be purged from the gene pool, and yet decades of genome-wide association and model organism studies have shown that they persist. One potential explanation is that alleles that regulate lifespan do so only in certain environmental contexts. We exposed outbred Drosophila to control and high-sugar diets and genotyped more than 10,000 adult flies to track allele frequency changes over the course of a single adult lifespan. We identified thousands of lifespan-associated alleles associated with early versus late-life trade-offs, late-onset effects and genotype-by-environment interactions. Remarkably, a third of lifespan-associated genetic variation had environmentally dependent effects on lifespan. We find that lifespan-reducing alleles are often recently derived, have stronger effects on a high-sugar diet and show signatures of selection in wild Drosophila populations, consistent with the evolutionary mismatch hypothesis. Our results provide insight into the highly polygenic and context-dependent genetic architecture of lifespan variation and the evolutionary processes that shape this key trait.

Original languageEnglish (US)
Pages (from-to)123-129
Number of pages7
JournalNature Genetics
Volume55
Issue number1
DOIs
StatePublished - Jan 2023

All Science Journal Classification (ASJC) codes

  • Genetics

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