An Incompatibility between a Mitochondrial tRNA and Its Nuclear-Encoded tRNA Synthetase Compromises Development and Fitness in Drosophila

Colin D Meiklejohn, Marissa A. Holmbeck, Mohammad A. Siddiq, Dawn N. Abt, David M. Rand, Kristi L. Montooth

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

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 tRNATyr 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.

Original languageEnglish (US)
Article numbere1003238
JournalPLoS genetics
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

nuclear-cytoplasmic interactions
Amino Acyl-tRNA Synthetases
incompatibility
Transfer RNA
ligases
translation (genetics)
Drosophila
polymorphism
Tyrosine-tRNA Ligase
fitness
RNA, Transfer, Tyr
genome
genetic polymorphism
NADH dehydrogenase (ubiquinone)
epistasis
penetrance
Mitochondrial Diseases
Drosophila simulans
Mitochondrial Genome
Molecular Evolution

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

An Incompatibility between a Mitochondrial tRNA and Its Nuclear-Encoded tRNA Synthetase Compromises Development and Fitness in Drosophila. / Meiklejohn, Colin D; Holmbeck, Marissa A.; Siddiq, Mohammad A.; Abt, Dawn N.; Rand, David M.; Montooth, Kristi L.

In: PLoS genetics, Vol. 9, No. 1, e1003238, 01.01.2013.

Research output: Contribution to journalArticle

Meiklejohn, Colin D ; Holmbeck, Marissa A. ; Siddiq, Mohammad A. ; Abt, Dawn N. ; Rand, David M. ; Montooth, Kristi L. / An Incompatibility between a Mitochondrial tRNA and Its Nuclear-Encoded tRNA Synthetase Compromises Development and Fitness in Drosophila. In: PLoS genetics. 2013 ; Vol. 9, No. 1.
@article{80305d93a4f44d61a8eace109f493118,
title = "An Incompatibility between a Mitochondrial tRNA and Its Nuclear-Encoded tRNA Synthetase Compromises Development and Fitness in Drosophila",
abstract = "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 tRNATyr 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.",
author = "Meiklejohn, {Colin D} and Holmbeck, {Marissa A.} and Siddiq, {Mohammad A.} and Abt, {Dawn N.} and Rand, {David M.} and Montooth, {Kristi L.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1371/journal.pgen.1003238",
language = "English (US)",
volume = "9",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - An Incompatibility between a Mitochondrial tRNA and Its Nuclear-Encoded tRNA Synthetase Compromises Development and Fitness in Drosophila

AU - Meiklejohn, Colin D

AU - Holmbeck, Marissa A.

AU - Siddiq, Mohammad A.

AU - Abt, Dawn N.

AU - Rand, David M.

AU - Montooth, Kristi L.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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 tRNATyr 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.

AB - 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 tRNATyr 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.

UR - http://www.scopus.com/inward/record.url?scp=84873512878&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873512878&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1003238

DO - 10.1371/journal.pgen.1003238

M3 - Article

VL - 9

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 1

M1 - e1003238

ER -