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Edward McAssey
The relative importance of interactions between mitochondrial and nuclear genes on adaptation has gained increased attention (see Wolff et al., 2014), although experimental systems to make direct tests of its importance are scarce. Mitonuclear epistasis is when nuclear and mitochondrial genes interact, often at the protein level, and variation in these interactions may result in phenotypic differences (Paliwal et al., 2014). These interactions are often found in the mitochondria where the energy-generating electron transport chain (ETC) is located, and consists of both nuclear and mitochondrial proteins...
December 6, 2016: Evolution; International Journal of Organic Evolution
Heming Wang, Yoonha Choi, Bamidele Tayo, Xuefeng Wang, Nathan Morris, Xiang Zhang, Uli Broeckel, Craig Hanis, Sharon Kardia, Susan Redline, Richard S Cooper, Hua Tang, Xiaofeng Zhu
The role played by epistasis between alleles at unlinked loci in shaping population fitness has been debated for many years and the existing evidence has been mainly accumulated from model organisms. In model organisms, fitness epistasis can be systematically inferred by detecting nonindependence of genotypic values between loci in a population and confirmed through examining the number of offspring produced in two-locus genotype groups. No systematic study has been conducted to detect epistasis of fitness in humans owing to experimental constraints...
December 5, 2016: Genetic Epidemiology
Lieve Desbonnet, Rachel Cox, Orna Tighe, Donna Lai, Richard P Harvey, John L Waddington, Colm M P O'Tuathaigh
The complex genetic origins of many human disorders suggest that epistatic (gene×gene) interactions may contribute to a significant proportion of their heritability estimates and phenotypic heterogeneity. Simultaneous disruption of the developmental genes and schizophrenia risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) in mice has been shown to produce disease-relevant and domain-specific phenotypic profiles different from that observed following disruption of either gene alone. In the current study, anxiety and stress responsivity phenotypes in male and female mutant mice with simultaneous disruption of DISC1 and NRG1 were examined...
December 1, 2016: Behavioural Brain Research
Maria Brbić, Matija Piškorec, Vedrana Vidulin, Anita Kriško, Tomislav Šmuc, Fran Supek
Bacteria and Archaea display a variety of phenotypic traits and can adapt to diverse ecological niches. However, systematic annotation of prokaryotic phenotypes is lacking. We have therefore developed ProTraits, a resource containing ∼545 000 novel phenotype inferences, spanning 424 traits assigned to 3046 bacterial and archaeal species. These annotations were assigned by a computational pipeline that associates microbes with phenotypes by text-mining the scientific literature and the broader World Wide Web, while also being able to define novel concepts from unstructured text...
December 1, 2016: Nucleic Acids Research
Hantao Wang, Cong Huang, Wenxia Zhao, Baosheng Dai, Chao Shen, Beibei Zhang, Dingguo Li, Zhongxu Lin
Two immortalized backcross populations (DHBCF1s and JMBCF1s) were developed using a recombinant inbred line (RIL) population crossed with the two parents DH962 and Jimian5 (as the males), respectively. The fiber quality and yield component traits of the two backcross populations were phenotyped at four environments (two locations, two years). One hundred seventy-eight quantitative trait loci (QTL) were detected including 76 for fiber qualities and 102 for yield components, explaining 4.08-17.79% of the phenotypic variation (PV)...
2016: PloS One
Michael D Bradley, Devin Neu, Fatmagul Bahar, Roy D Welch
In theory, a few naturally occurring evolutionary changes in the genome of a model organism may have little or no observable impact on its wild type phenotype, and yet still substantially impact the phenotypes of mutant strains through epistasis. To see if this is happening in a model organism, we obtained nine different laboratories' wild type Myxococcus xanthus DK1622 "sublines" and sequenced each to determine if they had evolved after their physical separation. Under a common garden experiment, each subline satisfied the phenotypic prerequisites for wild type, but many differed to a significant degree in each of the four quantitative phenotypic traits we measured, with some sublines differing by several-fold...
December 1, 2016: Scientific Reports
N H Barton
Much of quantitative genetics is based on the 'infinitesimal model', under which selection has a negligible effect on the genetic variance. This is typically justified by assuming a very large number of loci with additive effects. However, it applies even when genes interact, provided that the number of loci is large enough that selection on each of them is weak relative to random drift. In the long term, directional selection will change allele frequencies, but even then, the effects of epistasis on the ultimate change in trait mean due to selection may be modest...
November 30, 2016: Heredity
Dan He, Laxmi Parida
Quantitative genetic trait prediction based on high-density genotyping arrays plays an important role for plant and animal breeding, as well as genetic epidemiology such as complex diseases. The prediction can be very helpful to develop breeding strategies and is crucial to translate the findings in genetics to precision medicine. Epistasis, the phenomena where the SNPs interact with each other, has been studied extensively in Genome Wide Association Studies (GWAS) but received relatively less attention for quantitative genetic trait prediction...
2016: Pacific Symposium on Biocomputing
Joshua S Greene, May Dobosiewicz, Rebecca A Butcher, Patrick T McGrath, Cornelia I Bargmann
Natural isolates of C. elegans differ in their sensitivity to pheromones that inhibit exploratory behavior. Previous studies identified a QTL for pheromone sensitivity that includes alternative alleles of srx-43, a chemoreceptor that inhibits exploration through its activity in ASI sensory neurons. Here we show that the QTL is multigenic and includes alternative alleles of srx-44, a second chemoreceptor gene that modifies pheromone sensitivity. srx-44 either promotes or inhibits exploration depending on its expression in the ASJ or ADL sensory neurons, respectively...
November 28, 2016: ELife
Ronald M Levy, Allan Haldane, William F Flynn
Potts Hamiltonian models of protein sequence co-variation are statistical models constructed from the pair correlations observed in a multiple sequence alignment (MSA) of a protein family. These models are powerful because they capture higher order correlations induced by mutations evolving under constraints and help quantify the connections between protein sequence, structure, and function maintained through evolution. We review recent work with Potts models to predict protein structure and sequence-dependent conformational free energy landscapes, to survey protein fitness landscapes and to explore the effects of epistasis on fitness...
November 18, 2016: Current Opinion in Structural Biology
Erik D Nelson, Nick V Grishin
Recent analyses of amino acid mutations in proteins reveal that mutations at many pairs of sites are epistatic-i.e., their effects on fitness are non-additive-the combined effect of two mutations being significantly larger or smaller than the sum of their effects considered independently. Interestingly, epistatic sites are not necessarily near each other in the folded structure of a protein, and may even be located on opposite sides of a molecule. However, the mechanistic reasons for long-range epistasis remain obscure...
2016: PloS One
Serge Sverdlov, Elizabeth Thompson
We develop computational tools for the analysis of nonlinear genotype-phenotype relationships with epistasis among multiple loci or dominance interactions among multiple alleles within the same locus. Theory distinguishes between separable traits, with removable epistasis, and traits with essential epistasis. Separable traits can be transformed to a natural scale where additive methods apply. The methods we present solve for the natural scale, exactly when possible and approximately when not. Through graph methods, our methods allow for enumeration, counting, or sampling of distinct trait architectures satisfying constraints from the separability theory...
November 21, 2016: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
Claudia Bank, Sebastian Matuszewski, Ryan T Hietpas, Jeffrey D Jensen
The study of fitness landscapes, which aims at mapping genotypes to fitness, is receiving ever-increasing attention. Novel experimental approaches combined with next-generation sequencing (NGS) methods enable accurate and extensive studies of the fitness effects of mutations, allowing us to test theoretical predictions and improve our understanding of the shape of the true underlying fitness landscape and its implications for the predictability and repeatability of evolution. Here, we present a uniquely large multiallelic fitness landscape comprising 640 engineered mutants that represent all possible combinations of 13 amino acid-changing mutations at 6 sites in the heat-shock protein Hsp90 in Saccharomyces cerevisiae under elevated salinity...
November 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
P C Zee, J Liu, G J Velicer
Understanding how multiple mutations interact to jointly impact multiple ecologically important traits is critical for creating a robust picture of organismal fitness and the process of adaptation. However, this is complicated by both environmental heterogeneity and the complexity of genotype-to-phenotype relationships generated by pleiotropy and epistasis. Moreover, little is known about how pleiotropic and epistatic relationships themselves change over evolutionary time. The soil bacterium Myxococcus xanthus employs several distinct social traits across a range of environments...
October 19, 2016: Journal of Evolutionary Biology
Mirko Đorđević, Biljana Stojković, Uroš Savković, Elina Immonen, Nikola Tucić, Jelica Lazarević, Göran Arnqvist
The role of mitochondrial DNA for the evolution of life-history traits remains debated. We examined mitonuclear effects on the activity of the multisubunit complex of the electron transport chain (ETC) involved in oxidative phosphorylation (OXPHOS) across lines of the seed beetle Acanthoscelides obtectus selected for a short (E) or a long (L) life for more than >160 generations. We constructed and phenotyped mitonuclear introgression lines, which allowed us to assess the independent effects of the evolutionary history of the nuclear and the mitochondrial genome...
November 9, 2016: Evolution; International Journal of Organic Evolution
Elise Walck-Shannon, Bethany Lucas, Ian Chin-Sang, David Reiner, Kraig Kumfer, Hunter Cochran, William Bothfeld, Jeff Hardin
Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis...
November 2016: PLoS Genetics
Arnaud Le Rouzic, José M Álvarez-Castro
Understanding and predicting evolution is a central challenge in both population and quantitative genetics. The amount of genetic variance for quantitative traits available in a population conditions the particular way in which this population will (or will not) evolve under natural or artificial selection. Here, we explore the potential of gene-gene interactions (epistasis) to induce evolutionary plateaus at which evolutionary change virtually collapses for a number of generations, followed by the release of previously cryptic genetic variation...
December 2016: American Naturalist
Daniel A Peterson, Nate B Hardy, Benjamin B Normark
A long-standing hypothesis asserts that plant-feeding insects specialize on particular host plants because of negative interactions (trade-offs) between adaptations to alternative hosts, yet empirical evidence for such trade-offs is scarce. Most studies have looked for microevolutionary performance trade-offs within insect species, but host use could also be constrained by macroevolutionary trade-offs caused by epistasis and historical contingency. Here we used a phylogenetic approach to estimate the micro- and macroevolutionary correlations between use of alternative host-plant taxa within two major orders of plant-feeding insects: Lepidoptera (caterpillars) and Hemiptera (true bugs)...
December 2016: American Naturalist
Rishika De, Shefali S Verma, Emily Holzinger, Molly Hall, Amber Burt, David S Carrell, David R Crosslin, Gail P Jarvik, Helena Kuivaniemi, Iftikhar J Kullo, Leslie A Lange, Matthew B Lanktree, Eric B Larson, Kari E North, Alex P Reiner, Vinicius Tragante, Gerard Tromp, James G Wilson, Folkert W Asselbergs, Fotios Drenos, Jason H Moore, Marylyn D Ritchie, Brendan Keating, Diane Gilbert-Diamond
Genetic loci explain only 25-30 % of the heritability observed in plasma lipid traits. Epistasis, or gene-gene interactions may contribute to a portion of this missing heritability. Using the genetic data from five NHLBI cohorts of 24,837 individuals, we combined the use of the quantitative multifactor dimensionality reduction (QMDR) algorithm with two SNP-filtering methods to exhaustively search for SNP-SNP interactions that are associated with HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG)...
November 15, 2016: Human Genetics
Rachel Schell, Martin Mullis, Ian M Ehrenreich
Disruption of certain genes alters the heritable phenotypic variation among individuals. Research on the chaperone Hsp90 has played a central role in determining the genetic basis of this phenomenon, which may be important to evolution and disease. Key studies have shown that Hsp90 perturbation modifies the effects of many genetic variants throughout the genome. These modifications collectively transform the genotype-phenotype map, often resulting in a net increase or decrease in heritable phenotypic variation...
November 2016: PLoS Biology
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