Genetics. Published Articles Ahead of Print: October 11, 2005, Copyright © 2005
doi:10.1534/genetics.105.046698


A more recent version of this article appeared on January 1, 2006.

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Nuclear-mitochondrial epistasis and Drosophila aging: Introgression of D. simulans mtDNA modifies longevity in D. melanogaster nuclear backgrounds

David M Rand 1*, Adam J Fry 2 and Lea A Sheldahl 3

1 Brown University
2 University of Connecticut
3 Tufts University

* To whom correspondence should be addressed. E-mail: david_rand{at}brown.edu.

Submitted on June 9, 2005
Revised on September 4, 2005
Accepted on 28 September 2005


Abstract

Under the mitochondrial theory of aging, physiological decline with age results from the accumulated cellular damage produced by reactive oxygen species generated during electron transport in the mitochondrion. A large body of literature has documented age specific declines in mitochondrial function that are consistent with this theory, but relatively few studies have been able to distinguish cause from consequence in the association between mitochondrial function and aging. Since mitochondrial function is jointly encoded by mitochondrial (mtDNA) and nuclear genes, the mitochondrial genetics of aging should be controlled by variation in: 1) mtDNA, 2) nuclear genes, or 3) nuclear-mtDNA interactions. The goal of this study was to assess the relative contributions of these factors in causing variation in Drosophila longevity. We compared strains of flies carrying mtDNAs with varying levels of divergence: two strains from Zimbabwe (< 20 bp substitutions between mtDNAs), strains from Crete and USA (~20-40 bp substitutions between mtDNAs) and introgression strains of D. melanogaster carrying mtDNA from D. simulans in a D. melanogaster Oregon R chromosomal background (> 500 silent and 80 amino acid substitutions between these mtDNAs). Longevity was studied in reciprocal cross genotypes between pairs of these strains to test for cytoplasmic (mtDNA) factors affecting aging. The intrapopulation crosses between Zimbabwe strains show no difference in longevity between mtDNAs; the interpopulation crosses between Crete and USA show subtle but significant differences in longevity; and the interspecific introgression lines showed very significant differences between mtDNAs. However, the genotypes carrying the D. simulans mtDNA were not consistently short-lived, as might be predicted from the disruption of nuclear-mitochondrial coadaptation. Rather, the interspecific mtDNA strains showed a wide range of variation that flanked the longevities seen between intraspecific mtDNAs, resulting in very significant nuclear x mtDNA epistatic interaction effects. These results suggest that even 'defective' mtDNA haplotypes could extend longevity in different nuclear allelic backgrounds, which could account for the variable effects attributable to mtDNA haplogroups in human aging.

Key Words: aging, coadaptation, cytonuclear, epistasis, mitonuclear




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