title: Evolved genetic and phenotypic differences due to mitochondrial-nuclear interactions.
abstract: The oxidative phosphorylation (OxPhos) pathway is responsible for most aerobic ATP production and is the only pathway with both nuclear and mitochondrial encoded proteins. The importance of the interactions between these two genomes has recently received more attention because of their potential evolutionary effects and how they may affect human health and disease. In many different organisms, healthy nuclear and mitochondrial genome hybrids between species or among distant populations within a species affect fitness and OxPhos functions. However, what is less understood is whether these interactions impact individuals within a single natural population. The significance of this impact depends on the strength of selection for mito-nuclear interactions. We examined whether mito-nuclear interactions alter allele frequencies for ~11,000 nuclear SNPs within a single, natural Fundulus heteroclitus population containing two divergent mitochondrial haplotypes (mt-haplotypes). Between the two mt-haplotypes, there are significant nuclear allele frequency differences for 349 SNPs with a p-value of 1% (236 with 10% FDR). Unlike the rest of the genome, these 349 outlier SNPs form two groups associated with each mt-haplotype, with a minority of individuals having mixed ancestry. We use this mixed ancestry in combination with mt-haplotype as a polygenic factor to explain a significant fraction of the individual OxPhos variation. These data suggest that mito-nuclear interactions affect cardiac OxPhos function. The 349 outlier SNPs occur in genes involved in regulating metabolic processes but are not directly associated with the 79 nuclear OxPhos proteins. Therefore, we postulate that the evolution of mito-nuclear interactions affects OxPhos function by acting upstream of OxPhos.
authors.affiliation: Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, Rickenbacker Causeway, Miami, FL, United States of America.
authors.forename: Tara Z
authors.initials: TZ
authors.lastname: Baris
authors.affiliation: Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, Rickenbacker Causeway, Miami, FL, United States of America.
authors.forename: Dominique N
authors.initials: DN
authors.lastname: Wagner
authors.affiliation: Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, Rickenbacker Causeway, Miami, FL, United States of America.
authors.forename: David I
authors.initials: DI
authors.lastname: Dayan
authors.affiliation: Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, Rickenbacker Causeway, Miami, FL, United States of America.
authors.forename: Xiao
authors.initials: X
authors.lastname: Du
authors.affiliation: Dept de Biologie, Université du Québec à Rimouski, 300 Allée des Ursulines, Rimouski, Quebec, Canada.
authors.forename: Pierre U
authors.initials: PU
authors.lastname: Blier
authors.affiliation: Dept de Biologie, Université du Québec à Rimouski, 300 Allée des Ursulines, Rimouski, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pichaud
authors.affiliation: Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, Rickenbacker Causeway, Miami, FL, United States of America.
authors.forename: Marjorie F
authors.initials: MF
authors.lastname: Oleksiak
authors.affiliation: Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, Rickenbacker Causeway, Miami, FL, United States of America.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Crawford
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D023781:Fundulidae / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D015810:Linkage Disequilibrium; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D004272:DNA, Mitochondrial; D029941:Fish Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins