title: The Genomic Basis of Postponed Senescence in Drosophila melanogaster.
abstract: 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 < 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 Drosophila lifespan, most are novel and constitute a rich resource for future functional validation.
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Megan Ulmer
authors.initials: MU
authors.lastname: Carnes
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Terry
authors.initials: T
authors.lastname: Campbell
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America; Program in Genetics, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Butler
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America; Program in Genetics, North Carolina State University, Raleigh, North Carolina, 27695, United States of America; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Mary Anna
authors.initials: MA
authors.lastname: Carbone
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Duncan
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Sasha V
authors.initials: SV
authors.lastname: Harbajan
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Edward M
authors.initials: EM
authors.lastname: King
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Kara R
authors.initials: KR
authors.lastname: Peterson
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Weitzel
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America; Program in Genetics, North Carolina State University, Raleigh, North Carolina, 27695, United States of America; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, 27695, United States of America; Program in Genetics, North Carolina State University, Raleigh, North Carolina, 27695, United States of America; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, North Carolina, 27695, United States of America.
authors.forename: Trudy F C
authors.initials: TF
authors.lastname: Mackay
mesh_terms: D000375:Aging / Q000235:genetics*; D000483:Alleles; D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D017344:Genes, Insect / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D023281:Genomics / Q000379:methods; D008136:Longevity / Q000235:genetics; D008297:Male