Abstract
Natural selection acts to maximize reproductive fitness. However, antagonism between life span and reproductive success frequently poses a dilemma pitting the cost of fecundity against longevity. Here, we show that natural populations of Drosophila melanogaster harbor a Hoppel transposon insertion variant in the longevity gene Indy (I'm not dead yet), which confers both increased reproduction and longevity through metabolic changes. Heterozygosity for this natural long-lived variant has been maintained in isolates despite long-term inbreeding under laboratory conditions and advantageously confers increased fecundity. DNA sequences of variant chromosome isolates show evidence of selective sweep acting on the advantageous allele, suggesting that natural selection acts to maintain this variant. The transposon insertion also regulates Indy expression level, which has experimentally been shown to affect life span and fecundity. Thus, in the wild, evolution reaffirms that the mechanism of heterozygote advantage has acted upon the Indy gene to assure increased reproductive fitness and, coincidentally, longer life span through regulatory transposon mutagenesis.
Highlights
The genetic basis of longevity in species ranging from yeast to mammals has been investigated primarily through experimental alteration of expression in individual genes
We found that Drosophila isolates from around the world vary with respect to a naturally occurring polymorphism caused by the insertion of a transposable element, Hoppel
Hoppel polymorphism is found in Drosophila isolates from around the world In the course of our molecular analyses of Indy gene structure in different Drosophila isolates from around the globe, we found a natural polymorphism present in numerous independent populations
Summary
The genetic basis of longevity in species ranging from yeast to mammals has been investigated primarily through experimental alteration of expression in individual genes. Fewer studies have investigated the genetic architecture of longevity in natural populations at the level of molecular function [1]. It has been proposed that Indy mutations act to regulate the levels of tricarboxylic acid cycle (TCA) intermediates (e.g. citrate, succinate) via effects on transport, effectively inducing a genetic form of caloric restriction (CR) [4, 6], an intervention known to extend life span. We found that Drosophila isolates from around the world vary with respect to a naturally occurring polymorphism caused by the insertion of a transposable element, Hoppel. This mobile element has inserted into the first intron of the Indy gene, and we show that it is often maintained in a heterozygous state. We provide evidence for a selective sweep in the region where Hoppel has inserted, a molecular signature of recent positive selection acting on DNA sequences at the population level
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