Title: Mitochondria, sex and variation in routine metabolic rate
Abstract
Variation in the metabolic costs associated with organismal maintenance may play a key role in determining fitness, and thus these differences among individuals are likely to be subject to natural selection. Although the evolvability of maintenance metabolism depends on its underlying genetic architecture, relatively little is known about the nature of genetic variation that underlies this trait. To address this, we measured variation in routine metabolic rate (ṀO2routine), an index of maintenance metabolism, within and among three populations of Atlantic killifish,Fundulus heteroclitus, including a population from a region of genetic admixture between two subspecies. Polygenic association tests among individuals from the admixed population identified 54 single nucleotide polymorphisms (SNPs) that were associated withṀO2routine, and these SNPs accounted for 43% of interindividual variation in this trait. However, genetic associations withṀO2routineinvolved different SNPs if females and males were analysed separately, and there was a sex‐dependent effect of mitochondrial genotype on variation in routine metabolism. These results imply that there are sex‐specific genetic mechanisms, and potential mitonuclear interactions, that underlie variation inṀO2routine. Additionally, there was evidence for epistatic interactions between 17% of the possible pairs of trait‐associated SNPs, suggesting that epistatic effects onṀO2routineare common. These data demonstrate not only that phenotypic variation in this ecologically important trait has a polygenic basis with considerable epistasis among loci, but also that these underlying genetic mechanisms, and particularly the role of mitochondrial genotype, may be sex‐specific.
Genetic association studies that seek to explain the inheritance of complex traits typically fail to explain a majority of the heritability of the trait under study. Thus, we are left with a gap in the map from genotype to phenotype. Several approaches have been used to fill this gap, including those that attempt to map endophenotype such as the transcriptome, proteome or metabolome, that underlie complex traits. Here we used metabolomics to explore the nature of genetic variation for hydrogen peroxide (H2O2) resistance in the sequenced inbredDrosophilaGenetic Reference Panel (DGRP).
Results
We first studied genetic variation for H2O2resistance in 179 DGRP lines and along with identifying the insulin signaling modulatoru-shapedand several regulators of feeding behavior, we estimate that a substantial amount of phenotypic variation can be explained by a polygenic model of genetic variation. We then profiled a portion of the aqueous metabolome in subsets of eight ‘high resistance’ lines and eight ‘low resistance’ lines. We used these lines to represent collections of genotypes that were either resistant or sensitive to the stressor, effectively modeling a discrete trait. Across the range of genotypes in both populations, flies exhibited surprising consistency in their metabolomic signature of resistance. Importantly, the resistance phenotype of these flies was more easily distinguished by their metabolome profiles than by their genotypes. Furthermore, we found a metabolic response to H2O2in sensitive, but not in resistant genotypes. Metabolomic data further implicated at least two pathways, glycogen and folate metabolism, as determinants of sensitivity to H2O2. We also discovered a confounding effect of feeding behavior on assays involving supplemented food.
Conclusions
This work suggests that the metabolome can be a point of convergence for genetic variation influencing complex traits, and can efficiently elucidate mechanisms underlying trait variation.
Everman, Elizabeth R.; Macdonald, Stuart J.; Kelly, John K.(
, Frontiers in Genetics)
Introduction:Heavy metal pollutants can have long lasting negative impacts on ecosystem health and can shape the evolution of species. The persistent and ubiquitous nature of heavy metal pollution provides an opportunity to characterize the genetic mechanisms that contribute to metal resistance in natural populations.
Methods:We examined variation in resistance to copper, a common heavy metal contaminant, using wild collections of the model organismDrosophila melanogaster. Flies were collected from multiple sites that varied in copper contamination risk. We characterized phenotypic variation in copper resistance within and among populations using bulked segregant analysis to identify regions of the genome that contribute to copper resistance.
Results and Discussion:Copper resistance varied among wild populations with a clear correspondence between resistance level and historical exposure to copper. We identified 288 SNPs distributed across the genome associated with copper resistance. Many SNPs had population-specific effects, but some had consistent effects on copper resistance in all populations. Significant SNPs map to several novel candidate genes involved in refolding disrupted proteins, energy production, and mitochondrial function. We also identified one SNP with consistent effects on copper resistance in all populations nearCG11825, a gene involved in copper homeostasis and copper resistance. We compared the genetic signatures of copper resistance in the wild-derived populations to genetic control of copper resistance in theDrosophilaSynthetic Population Resource (DSPR) and theDrosophilaGenetic Reference Panel (DGRP), two copper-naïve laboratory populations. In addition toCG11825, which was identified as a candidate gene in the wild-derived populations and previously in the DSPR, there was modest overlap of copper-associated SNPs between the wild-derived populations and laboratory populations. Thirty-one SNPs associated with copper resistance in wild-derived populations fell within regions of the genome that were associated with copper resistance in the DSPR in a prior study. Collectively, our results demonstrate that the genetic control of copper resistance is highly polygenic, and that several loci can be clearly linked to genes involved in heavy metal toxicity response. The mixture of parallel and population-specific SNPs points to a complex interplay between genetic background and the selection regime that modifies the effects of genetic variation on copper resistance.
Turner, Kathryn G.; Ostevik, Kate L.; Grassa, Christopher J.; Rieseberg, Loren H.(
, Frontiers in Ecology and Evolution)
null
(Ed.)
Invasive species represent excellent opportunities to study the evolutionary potential of traits important to success in novel environments. Although some ecologically important traits have been identified in invasive species, little is typically known about the genetic mechanisms that underlie invasion success in non-model species. Here, we use a genome-wide association (GWAS) approach to identify the genetic basis of trait variation in the non-model, invasive, diffuse knapweed [ Centaurea diffusa Lam. (Asteraceae)]. To assist with this analysis, we have assembled the first draft genome reference and fully annotated plastome assembly for this species, and one of the first from this large, weedy, genus, which is of major ecological and economic importance. We collected phenotype data from 372 individuals from four native and four invasive populations of C. diffusa grown in a common environment. Using these individuals, we produced reduced-representation genotype-by-sequencing (GBS) libraries and identified 7,058 SNPs. We identify two SNPs associated with leaf width in these populations, a trait which significantly varies between native and invasive populations. In this rosette forming species, increased leaf width is a major component of increased biomass, a common trait in invasive plants correlated with increased fitness. Finally, we use annotations from Arabidopsis thaliana to identify 98 candidate genes that are near the associated SNPs and highlight several good candidates for leaf width variation.
Crawford, D. L.
Schulte(
, Comprehensive physiology)
By investigating evolutionary adaptations that change physiological functions, we can enhance our understanding of how organisms work, the importance of physiological traits, and the genes that influence these traits. This approach of investigating the evolution of physiological adaptation has been used with the teleost fish Fundulus heteroclitus and has produced insights into (i) how protein polymorphisms enhance swimming and development; (ii) the role of equilibrium enzymes in modulating metabolic flux; (iii) how variation in DNA sequences and mRNA expression patterns mitigate changes in temperature, pollution, and salinity; and (iv) the importance of nuclear-mitochondrial genome interactions for energy metabolism. Fundulus heteroclitus provides so many examples of adaptive evolution because their local population sizes are large, they have significant standing genetic variation, and they experience large ranges of environmental conditions that enhance the likelihood that adaptive evolution will occur. Thus, F. heteroclitus research takes advantage of evolutionary changes associated with exposure to diverse environments, both across the North American Atlantic coast and within local habitats, to contrast neutral versus adaptive divergence. Based on evolutionary analyses contrasting neutral and adaptive evolution in F. heteroclitus populations, we conclude that adaptive evolution can occur readily and rapidly, at least in part because it depends on large amounts of standing genetic variation among many genes that can alter physiological traits. These observations of polygenic adaptation enhance our understanding of how evolution and physiological adaptation progresses, thus informing both biological and medical scientists about genotype-phenotype relationships
Abstract The genetic basis of traits shapes and constrains how adaptation proceeds in nature; rapid adaptation can proceed using stores of polygenic standing genetic variation or hard selective sweeps, and increasing polygenicity fuels genetic redundancy, reducing gene re-use (genetic convergence). Guppy life history traits evolve rapidly and convergently among natural high- and low-predation environments in northern Trinidad. This system has been studied extensively at the phenotypic level, but little is known about the underlying genetic architecture. Here, we use four independent F2 QTL crosses to examine the genetic basis of seven (five female, two male) guppy life history phenotypes and discuss how these genetic architectures may facilitate or constrain rapid adaptation and convergence. We use RAD-sequencing data (16,539 SNPs) from 370 male and 267 female F2 individuals. We perform linkage mapping, estimates of genome-wide and per-chromosome heritability (multi-locus associations), and QTL mapping (single-locus associations). Our results are consistent with architectures of many loci of small-effect for male age and size at maturity and female interbrood period. Male trait associations are clustered on specific chromosomes, but female interbrood period exhibits a weak genome-wide signal suggesting a potentially highly polygenic component. Offspring weight and female size at maturity are also associated with a single significant QTL each. These results suggest rapid, repeatable phenotypic evolution of guppies may be facilitated by polygenic trait architectures, but subsequent genetic redundancy may limit gene re-use across populations, in agreement with an absence of strong signatures of genetic convergence from recent analyses of wild guppies.
Healy, Timothy M., Brennan, Reid S., Whitehead, Andrew, and Schulte, Patricia M. Mitochondria, sex and variation in routine metabolic rate. Molecular Ecology 28.20 Web. doi:10.1111/mec.15244.
Healy, Timothy M., Brennan, Reid S., Whitehead, Andrew, & Schulte, Patricia M. Mitochondria, sex and variation in routine metabolic rate. Molecular Ecology, 28 (20). https://doi.org/10.1111/mec.15244
Healy, Timothy M., Brennan, Reid S., Whitehead, Andrew, and Schulte, Patricia M.
"Mitochondria, sex and variation in routine metabolic rate". Molecular Ecology 28 (20). Country unknown/Code not available: Wiley-Blackwell. https://doi.org/10.1111/mec.15244.https://par.nsf.gov/biblio/10376141.
@article{osti_10376141,
place = {Country unknown/Code not available},
title = {Mitochondria, sex and variation in routine metabolic rate},
url = {https://par.nsf.gov/biblio/10376141},
DOI = {10.1111/mec.15244},
abstractNote = {Abstract Variation in the metabolic costs associated with organismal maintenance may play a key role in determining fitness, and thus these differences among individuals are likely to be subject to natural selection. Although the evolvability of maintenance metabolism depends on its underlying genetic architecture, relatively little is known about the nature of genetic variation that underlies this trait. To address this, we measured variation in routine metabolic rate (ṀO2routine), an index of maintenance metabolism, within and among three populations of Atlantic killifish,Fundulus heteroclitus, including a population from a region of genetic admixture between two subspecies. Polygenic association tests among individuals from the admixed population identified 54 single nucleotide polymorphisms (SNPs) that were associated withṀO2routine, and these SNPs accounted for 43% of interindividual variation in this trait. However, genetic associations withṀO2routineinvolved different SNPs if females and males were analysed separately, and there was a sex‐dependent effect of mitochondrial genotype on variation in routine metabolism. These results imply that there are sex‐specific genetic mechanisms, and potential mitonuclear interactions, that underlie variation inṀO2routine. Additionally, there was evidence for epistatic interactions between 17% of the possible pairs of trait‐associated SNPs, suggesting that epistatic effects onṀO2routineare common. These data demonstrate not only that phenotypic variation in this ecologically important trait has a polygenic basis with considerable epistasis among loci, but also that these underlying genetic mechanisms, and particularly the role of mitochondrial genotype, may be sex‐specific.},
journal = {Molecular Ecology},
volume = {28},
number = {20},
publisher = {Wiley-Blackwell},
author = {Healy, Timothy M. and Brennan, Reid S. and Whitehead, Andrew and Schulte, Patricia M.},
}
Warning: Leaving National Science Foundation Website
You are now leaving the National Science Foundation website to go to a non-government website.
Website:
NSF takes no responsibility for and exercises no control over the views expressed or the accuracy of
the information contained on this site. Also be aware that NSF's privacy policy does not apply to this site.
