title: Nucleotide diversity inflation as a genome-wide response to experimental lifespan extension in Drosophila melanogaster.
abstract: Evolutionary theory predicts that antagonistically selected alleles, such as those with divergent pleiotropic effects in early and late life, may often reach intermediate population frequencies due to balancing selection, an elusive process when sought out empirically. Alternatively, genetic diversity may increase as a result of positive frequency-dependent selection and genetic purging in bottlenecked populations.
  
  
  
  While experimental evolution systems with directional phenotypic selection typically result in at least local heterozygosity loss, we report that selection for increased lifespan in Drosophila melanogaster leads to an extensive genome-wide increase of nucleotide diversity in the selected lines compared to replicate control lines, pronounced in regions with no or low recombination, such as chromosome 4 and centromere neighborhoods. These changes, particularly in coding sequences, are most consistent with the operation of balancing selection and the antagonistic pleiotropy theory of aging and life history traits that tend to be intercorrelated. Genes involved in antioxidant defenses, along with multiple lncRNAs, were among those most affected by balancing selection. Despite the overwhelming genetic diversification and the paucity of selective sweep regions, two genes with functions important for central nervous system and memory, Ptp10D and Ank2, evolved under positive selection in the longevity lines.
  
  
  
  Overall, the 'evolve-and-resequence' experimental approach proves successful in providing unique insights into the complex evolutionary dynamics of genomic regions responsible for longevity.
authors.affiliation: Biocomplexity Institute, Virginia Tech, 1015 Life Science Circle, Blacksburg, VA, 24061, USA. pawel@vbi.vt.edu.
authors.forename: Pawel
authors.initials: P
authors.lastname: Michalak
authors.affiliation: Biocomplexity Institute, Virginia Tech, 1015 Life Science Circle, Blacksburg, VA, 24061, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Bioscience, Aarhus University, Ny Munkegade 114-116, Aarhus, DK-8000, Denmark.
authors.forename: Pernille M
authors.initials: PM
authors.lastname: Sarup
authors.affiliation: Department of Bioscience, Aarhus University, Ny Munkegade 114-116, Aarhus, DK-8000, Denmark.
authors.forename: Mads F
authors.initials: MF
authors.lastname: Schou
authors.affiliation: Department of Bioscience, Aarhus University, Ny Munkegade 114-116, Aarhus, DK-8000, Denmark. volker@bios.au.dk.
authors.forename: Volker
authors.initials: V
authors.lastname: Loeschcke
mesh_terms: D000483:Alleles; D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D049750:Genome, Insect; D023281:Genomics / Q000379:methods; D006579:Heterozygote; D008136:Longevity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide