Compatibility between mitochondrial and nuclear genomes correlates with the quantitative trait of lifespan in Caenorhabditis elegans.

Zuobin Zhu,Fangfang Zeng,Junjing Wang,Qing Lu,Shi Huang

doi:10.1038/srep17303

Abstract

Mutations in mitochondrial genome have epistatic effects on organisms depending on the nuclear background, but a role for the compatibility of mitochondrial-nuclear genomes (mit-n) in the quantitative nature of a complex trait remains unexplored. We studied a panel of recombinant inbred advanced intercrossed lines (RIAILs) of C. elegans that were established from a cross between the N2 and HW strains. We determined the HW nuclear genome content and the mitochondrial type (HW or N2) of each RIAIL strain. We found that the degree of mit-n compatibility was correlated with the lifespans but not the foraging behaviors of RIAILs. Several known aging-associated QTLs individually showed no relationship with mitotypes but collectively a weak trend consistent with a role in mit-n compatibility. By association mapping, we identified 293 SNPs that showed linkage with lifespan and a relationship with mitotypes consistent with a role in mit-n compatibility. We further found an association between mit-n compatibility and several functional characteristics of mitochondria as well as the expressions of genes involved in the respiratory oxidation pathway. The results provide the first evidence implicating mit-n compatibility in the quantitative nature of a complex trait, and may be informative to certain evolutionary puzzles on hybrids.

Highlights

Are almost 900 genes with an eQTL, of which almost half were found to have a genotype-by-age effect[17]
We determined the lifespans of recombinant inbred advanced intercross lines (RIAILs) strains and found a positive correlation between HW allele content (HAC) and the lifespan of C. elegans in the HW mitochondria background (Fig. 1a, Supplementary Table S1)
We further found that there were no relationships between HAC and lifespan when ignoring the mitotype background (Fig. 1c)

Summary

Introduction

Are almost 900 genes with an eQTL, of which almost half were found to have a genotype-by-age effect[17]. A hybrid strain of C. elegans with the HW mitochondria in the N2 nuclear background had reduced median lifespan relative to the HW strain CB485626 While this result may be related to nuclear–mtDNA mismatch, it remains unknown whether this mismatch involves mainly certain specific loci such as the p.A12S amino acid or the whole set of mitochondrial and nuclear genome. We studied the quantitative variations in mit-n compatibility and the lifespan of a panel of RIAILs where difference in longevity among individual strains was a quantitative trait. These RIAILs differ from each other in many loci and a set of 1454 SNP markers spanning 98.6% of the physical length of the chromosomes had been previously genotyped[31]. We here present experimental evidence for the novel hypothesis that the quantitative trait of aging may be in part explained by the quantitative variations in the mit-n compatibility on a genome-wide scale

Methods

Results

Conclusion