RESUMEN
Mitochondrial transcription, translation, and respiration require interactions between genes encoded in two distinct genomes, generating the potential for mutations in nuclear and mitochondrial genomes to interact epistatically and cause incompatibilities that decrease fitness. Mitochondrial-nuclear epistasis for fitness has been documented within and between populations and species of diverse taxa, but rarely has the genetic or mechanistic basis of these mitochondrial-nuclear interactions been elucidated, limiting our understanding of which genes harbor variants causing mitochondrial-nuclear disruption and of the pathways and processes that are impacted by mitochondrial-nuclear coevolution. Here we identify an amino acid polymorphism in the Drosophila melanogaster nuclear-encoded mitochondrial tyrosyl-tRNA synthetase that interacts epistatically with a polymorphism in the D. simulans mitochondrial-encoded tRNA(Tyr) to significantly delay development, compromise bristle formation, and decrease fecundity. The incompatible genotype specifically decreases the activities of oxidative phosphorylation complexes I, III, and IV that contain mitochondrial-encoded subunits. Combined with the identity of the interacting alleles, this pattern indicates that mitochondrial protein translation is affected by this interaction. Our findings suggest that interactions between mitochondrial tRNAs and their nuclear-encoded tRNA synthetases may be targets of compensatory molecular evolution. Human mitochondrial diseases are often genetically complex and variable in penetrance, and the mitochondrial-nuclear interaction we document provides a plausible mechanism to explain this complexity.
Asunto(s)
Aminoacil-ARNt Sintetasas , Drosophila , Fosforilación Oxidativa , ARN de Transferencia , Aminoácidos , Aminoacil-ARNt Sintetasas/genética , Aminoacil-ARNt Sintetasas/metabolismo , Animales , Núcleo Celular/genética , Núcleo Celular/metabolismo , Drosophila/genética , Drosophila/crecimiento & desarrollo , Drosophila/fisiología , Epistasis Genética , Evolución Molecular , Aptitud Genética , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Enfermedades Mitocondriales , Datos de Secuencia Molecular , Polimorfismo Genético , ARN de Transferencia/genética , Tirosina-ARNt Ligasa/metabolismoRESUMEN
Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
Asunto(s)
Drosophila/clasificación , Drosophila/genética , Evolución Molecular , Genes de Insecto/genética , Genoma de los Insectos/genética , Genómica , Filogenia , Animales , Codón/genética , Elementos Transponibles de ADN/genética , Drosophila/inmunología , Drosophila/metabolismo , Proteínas de Drosophila/genética , Orden Génico/genética , Genoma Mitocondrial/genética , Inmunidad/genética , Familia de Multigenes/genética , ARN no Traducido/genética , Reproducción/genética , Alineación de Secuencia , Análisis de Secuencia de ADN , Sintenía/genéticaRESUMEN
To gain insight on mitochondrial DNA (mtDNA) evolution, we assembled and analyzed the mitochondrial genomes of Drosophila erecta, D. ananassae, D. persimilis, D. willistoni, D. mojavensis, D. virilis and D. grimshawi together with the sequenced mtDNAs of the melanogaster subgroup. Genomic comparisons across the well-defined Drosophila phylogeny impart power for detecting conserved mtDNA regions that maintain metabolic function and regions that evolve uniquely on lineages. Evolutionary rate varies across intergenic regions of the mtDNA. Rapidly evolving intergenic regions harbor the majority of mitochondrial indel divergence. In contrast, patterns of nearly perfect conservation within intergenic regions reveal a refined set of nucleotides underlying the binding of transcription termination factors. Sequencing of 5' cDNA ends indicates that cytochrome C oxidase I (CoI) has a novel (T/C)CG start codon and that perfectly conserved regions upstream of two NADH dehydrogenase (ND) genes are transcribed and likely extend these protein sequences. Substitutions at synonymous sites in the Drosophila mitochondrial proteomes reflect a mutation process that is biased toward A and T nucleotides and differs between mtDNA strands. Differences in codon usage bias across genes reveal that weak selection at silent sites may offset the mutation bias. The mutation-selection balance at synonymous sites has also diverged between the Drosophila and Sophophora lineages. Rates of evolution are highly heterogeneous across the mitochondrial proteome, with ND accumulating many more amino acid substitutions than CO. These oxidative phosphorylation complex-specific rates of evolution vary across lineages and may reflect physiological and ecological change across the Drosophila phylogeny.
Asunto(s)
ADN Mitocondrial/genética , Drosophila/genética , Evolución Molecular , Genoma Mitocondrial , Genómica/métodos , Secuencia de Aminoácidos , Animales , Composición de Base , Secuencia de Bases , Teorema de Bayes , Secuencia Conservada , ADN Intergénico , Proteínas del Complejo de Cadena de Transporte de Electrón/genética , Proteínas Mitocondriales/genética , Modelos Genéticos , Datos de Secuencia Molecular , Mutación , Filogenia , ARN de Transferencia/genética , Selección Genética , Alineación de Secuencia , Transcripción GenéticaRESUMEN
Efficient mitochondrial function requires physical interactions between the proteins encoded by the mitochondrial and nuclear genomes. Coevolution between these genomes may result in the accumulation of incompatibilities between divergent lineages. We test whether mitochondrial-nuclear incompatibilities have accumulated within the Drosophila melanogaster species subgroup by combining divergent mitochondrial and nuclear lineages and quantifying the effects on relative fitness. Precise placement of nine mtDNAs from D. melanogaster, D. simulans, and D. mauritiana into two D. melanogaster nuclear genetic backgrounds reveals significant mitochondrial-nuclear epistasis affecting fitness in females. Combining the mitochondrial genomes with three different D. melanogaster X chromosomes reveals significant epistasis for male fitness between X-linked and mitochondrial variation. However, we find no evidence that the more than 500 fixed differences between the mitochondrial genomes of D. melanogaster and the D. simulans species complex are incompatible with the D. melanogaster nuclear genome. Rather, the interactions of largest effect occur between mitochondrial and nuclear polymorphisms that segregate within species of the D. melanogaster species subgroup. We propose that a low mitochondrial substitution rate, resulting from a low mutation rate and/or efficient purifying selection, precludes the accumulation of mitochondrial-nuclear incompatibilities among these Drosophila species.