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1. The metabolome as a link in the genotype-phenotype map for peroxide resistance in the fruit fly, Drosophila melanogaster

   https://doi.org/10.1186/s12864-020-6739-1  

   Harrison, Benjamin R. ; Wang, Lu ; Gajda, Erika ; Hoffman, Elise V. ; Chung, Brian Y. ; Pletcher, Scott D. ; Raftery, Daniel ; Promislow, Daniel E. L. ( May 2020 , BMC Genomics)

   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).

   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.

   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.

    

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2. Evolutionary Physiology and Genomics in the Highly Adaptable Killifish (Fundulus heteroc

   https://doi.org/10.1002/cphy.c190004  

   Crawford, D. L. Schulte ( April 2020 , 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 

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3. The genetic basis of adaptation to copper pollution in Drosophila melanogaster

   https://doi.org/10.3389/fgene.2023.1144221  

   Everman, Elizabeth R. ; Macdonald, Stuart J. ; Kelly, John K. ( April 2023 , 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.

    

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4. Adaptive divergence in bill morphology and other thermoregulatory traits is facilitated by restricted gene flow in song sparrows on the California Channel Islands

   https://doi.org/10.1111/mec.16253  

   Gamboa, Maybellene P. ; Ghalambor, Cameron K. ; Scott Sillett, T. ; Morrison, Scott A. ; Chris Funk, W. ( November 2021 , Molecular Ecology)

   Disentangling the effects of neutral and adaptive processes in maintaining phenotypic variation across environmental gradients is challenging in natural populations. Song sparrows (Melospiza melodia) on the California Channel Islands occupy a pronounced east‐west climate gradient within a small spatial scale, providing a unique opportunity to examine the interaction of genetic isolation (reduced gene flow) and the environment (selection) in driving variation. We used reduced representation genomic libraries to infer the role of neutral processes (drift and restricted gene flow) and divergent selection in driving variation in thermoregulatory traits with an emphasis on the mechanisms that maintain bill divergence among islands. Analyses of 22,029 neutral SNPs confirm distinct population structure by island with restricted gene flow and relatively large effective population sizes, suggesting bill differences are probably not a product of genetic drift. Instead, we found strong support for local adaptation using 3294 SNPs in differentiation‐based and environmental association analyses coupled with genome‐wide association tests. Specifically, we identified several putatively adaptive and candidate loci in or near genes involved in bill development pathways (e.g.,BMP,CaM,Wnt), confirming the highly complex and polygenic architecture underlying bill morphology. Furthermore, we found divergence in genes associated with other thermoregulatory traits (i.e., feather structure, plumage colour, and physiology). Collectively, these results suggest strong divergent selection across an island archipelago results in genomic changes in a suite of traits associated with climate adaptation over small spatial scales. Future research should move beyond studying univariate traits to better understand multidimensional responses to complex environmental conditions.

    

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5. Heritability of interpack aggression in a wild pedigreed population of North American grey wolves

   https://doi.org/10.1111/mec.15349  

   vonHoldt, Bridgett M. ; DeCandia, Alexandra L. ; Heppenheimer, Elizabeth ; Janowitz‐Koch, Ilana ; Shi, Ruoyao ; Zhou, Hua ; German, Christopher A. ; Brzeski, Kristin E. ; Cassidy, Kira A. ; Stahler, Daniel R. ; et al ( January 2020 , Molecular Ecology)

   Aggression is a quantitative trait deeply entwined with individual fitness. Mapping the genomic architecture underlying such traits is complicated by complex inheritance patterns, social structure, pedigree information and gene pleiotropy. Here, we leveraged the pedigree of a reintroduced population of grey wolves (Canis lupus) in Yellowstone National Park, Wyoming, USA, to examine the heritability of and the genetic variation associated with aggression. Since their reintroduction, many ecological and behavioural aspects have been documented, providing unmatched records of aggressive behaviour across multiple generations of a wild population of wolves. Using a linear mixed model, a robust genetic relationship matrix, 12,288 single nucleotide polymorphisms (SNPs) and 111 wolves, we estimated the SNP‐based heritability of aggression to be 37% and an additional 14% of the phenotypic variation explained by shared environmental exposures. We identified 598 SNP genotypes from 425 grey wolves to resolve a consensus pedigree that was included in a heritability analysis of 141 individuals with SNP genotype, metadata and aggression data. The pedigree‐based heritability estimate for aggression is 14%, and an additional 16% of the phenotypic variation was explained by shared environmental exposures. We find strong effects of breeding status and relative pack size on aggression. Through an integrative approach, these results provide a framework for understanding the genetic architecture of a complex trait that influences individual fitness, with linkages to reproduction, in a social carnivore. Along with a few other studies, we show here the incredible utility of a pedigreed natural population for dissecting a complex, fitness‐related behavioural trait.

    

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