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Philip W. Hedrick - One of the best experts on this subject based on the ideXlab platform.

  • Heterozygote Advantage: The Effect of Artificial Selection in Livestock and Pets
    2016
    Co-Authors: Philip W. Hedrick
    Abstract:

    There are a number of mutants in livestock and pets that have a Heterozygote Advantage because of artificial selection for these mutants in Heterozygotes and strong detrimental effects from natural selection in homozygotes. In livestock, these mutants include ones that influence milk yield in dairy cattle, fecundity in sheep, litter size in pigs, muscling in beef cattle, color in horses, lean meat content in pigs, and comb morphology in chickens. In pets, these mutants include ones that influence tail length in cats and hairlessness, muscling, color, or ridgeback hair in dogs. A large variety of mutants are responsible, including small or large deletions or insertions and single base-pair nonsynonymous changes. Many of the mutants cause loss of function for the genes involved, a change that results in the pleiotropic effects of a desired phenotype in Heterozygotes and low fitness or an undesirable phenotype in mutant homozygotes. I examine how selection changes the frequency of these mutants and provide an approach to estimate the amount of artificial selection that is necessary to maintain these mutants at the high frequencies often observed. The amount of artificial selection ranges from low selection favoring Heterozygotes for double muscling in whippet dogs to very strong selection favoring the “flash ” (part white, part solid) Heterozygote in boxer dogs and the rose comb in chickens. In several examples (rose comb in Wyandotte chickens and the hair ridge in Rhodesian ridgeback dogs), there is actually stronger selection for the mutant than against it, making the frequency of the mutant greater than 50%. Subject areas: Molecular adaptation and selection, Genomics and gene mappin

  • examining the cause of high inbreeding depression analysis of whole genome sequence data in 28 selfed progeny of eucalyptus grandis
    New Phytologist, 2016
    Co-Authors: Philip W. Hedrick, Uffe Hellsten, Dario Grattapaglia
    Abstract:

    The genome-wide heterozygosity at 9590 genes, all heterozygous in a single Eucalyptus grandis parent tree, was examined in a group of 28 S1 offspring. Heterozygosity ranged from 52-79%, averaging 65.5%, much higher than the 50% expected under random segregation, supporting the occurrence of strong (47%) selection against homozygosity. The expected pattern of heterozygosity from theoretical calculations and simulations for recessive detrimentals (pseudo-overdominance) and intrinsic Heterozygote Advantage was examined and compared with that observed. The observed patterns are consistent with at least several detrimental loci with large effects on both parental chromosomes of the 11 pairs. It is likely that 100 or more genes, many with substantial effects on viability, are contributing to this inbreeding depression. Although our genome-wide analysis of nearly 10 000 genes strongly suggested that pseudo-overdominance was responsible for the observed high inbreeding depression, Heterozygote Advantage could not be excluded. Finding inconvertible evidence of the cause of inbreeding depression still presents a difficult challenge. This study is the first theoretical examination of the genomic effect of inbreeding in a forest tree and provides an approach to analyze these data to determine the extent and cause of inbreeding depression across other plant genomes.

  • Heterozygote Advantage: The Effect of Artificial Selection in Livestock and Pets
    Journal of Heredity, 2014
    Co-Authors: Philip W. Hedrick
    Abstract:

    There are a number of mutants in livestock and pets that have a Heterozygote Advantage because of artificial selection for these mutants in Heterozygotes and strong detrimental effects from natural selection in homozygotes. In livestock, these mutants include ones that influence milk yield in dairy cattle, fecundity in sheep, litter size in pigs, muscling in beef cattle, color in horses, lean meat content in pigs, and comb morphology in chickens. In pets, these mutants include ones that influence tail length in cats and hairlessness, muscling, color, or ridgeback hair in dogs. A large variety of mutants are responsible, including small or large deletions or insertions and single base-pair nonsynonymous changes. Many of the mutants cause loss of function for the genes involved, a change that results in the pleiotropic effects of a desired phenotype in Heterozygotes and low fitness or an undesirable phenotype in mutant homozygotes. I examine how selection changes the frequency of these mutants and provide an approach to estimate the amount of artificial selection that is necessary to maintain these mutants at the high frequencies often observed. The amount of artificial selection ranges from low selection favoring Heterozygotes for double muscling in whippet dogs to very strong selection favoring the “flash” (part white, part solid) Heterozygote in boxer dogs and the rose comb in chickens. In several examples (rose comb in Wyandotte chickens and the hair ridge in Rhodesian ridgeback dogs), there is actually stronger selection for the mutant than against it, making the frequency of the mutant greater than 50%.

  • Heterozygote Advantage in a finite population black color in wolves
    Journal of Heredity, 2014
    Co-Authors: Philip W. Hedrick, Daniel R Stahler, Dick Dekker
    Abstract:

    There is a striking color polymorphism for wolves in the Yellowstone National Park where approximately half the wolves are black. The genetic basis for this polymorphism is known, and fitnesses of the genotypes are estimated. These estimates sug gest that there is strong Heterozygote Advantage but substantial asymmetry in the fitness differences of the 2 homozygotes. Theoretically, such fitnesses in a finite population are thought to reduce genetic variation at least as fast as if there were no selection at all. Because the color polymorphism has remained at about the same frequency for 17 years , about 4 generations, we investigated whether this was consistent with the theoretical predictions. Counter to this general expectation of loss, given the initial frequency of black wolves, the theoretical expectation in this case was found to be that the frequency would only decline slowly over time. For example, if the effective population size is 20, then the expected black allele frequency after 4 generations would be 0.191, somewhat less than the observed value of 0.237. However, nearly 30% of the time the expected frequency is 0.25 or greater, consistent with the contemporary observed frequency. In other words and in contrast to general theoretical predictions, because of the short period of time in evolutionary terms and the relatively weak selection at low frequencies, the observed variation and the predicted theoretical variation are not inconsistent. Subject areas: Conser vation genetics and biodiversity

  • What is the evidence for Heterozygote Advantage selection
    Trends in Ecology and Evolution, 2012
    Co-Authors: Philip W. Hedrick
    Abstract:

    Recent genomic data have found that many genes show the signal of selection. How many of these genes are undergoing Heterozygote Advantage selection is only beginning to be known. Initial genomic surveys have suggested that only a small proportion of loci have polymorphisms maintained by Heterozygote Advantage and this is consistent with the few examples generated from other approaches within given species. Unless further studies provide large numbers of loci with Heterozygote Advantage, it appears that loci with Heterozygote Advantage must be considered only a small minority of all loci in a species. This is not to say that some Heterozygote Advantage loci do not have important adaptive functions, but that their role in overall evolutionary change might be more of an unusual phenomenon than a major player in adaptation.

Marian Annett - One of the best experts on this subject based on the ideXlab platform.

  • handedness and brain asymmetry the right shift theory
    2002
    Co-Authors: Marian Annett
    Abstract:

    Introduction. The Puzzle of Handedness and Cerebral Speech. The Right Shift Theory. Human Handedness: Discrete Types or Continuous Varieties? The Right Shift Theory of Handedness: Chance Plus or Minus Right Loading. A Right Shift Factor for Left Cerebral Dominance. The Single Gene Theory of Right Shift. Explorations in the Light of the Theory. Stability and Change: Handedness with Age, Sex and Time. A Single Gene with Variable Expression for Genotype, Sex and Twinning. Other Asymmetries of Brain and Behaviour. Predicting Associations Between Asymmetries. A Genetic Balanced Polymorphism with Heterozygote Advantage. Why Right Shift and Why Genetic Variability? The Advantages and DisAdvantages of the RS+ Gene. Heterozygote Advantage. What are the DisAdvantages of Right Shift? Spatial and Mathematical Reasoning, Art, Music, Surgery and Sport. Speech, Phonology and Varieties of Dyslexia: The Costs and Benefits of the RS+ Gene. Schizophrenia and Autism: The Theory of an Agnosic RS+ Gene. Independent Replications, Challenges and Theories. Independent Tests and Challenges. Alternative Theories or Variations on a Theme? Conclusions. Summary: What, How, and Why? Appendices.

  • Handedness and educational success: The hypothesis of a genetic balanced polymorphism with Heterozygote Advantage for laterality and ability
    British Journal of Development Psychology, 1993
    Co-Authors: Marian Annett
    Abstract:

    A sample of children assessed for hand preference and hand skill at 14–15 years could be classified on two independent measures of educational success. One was whether they had been selected or not selected for grammar school two years earlier; the other was the performance of unselected children in the examinations of the General Certificate of Secondary Education (GCSE) some 18 months later. There were no differences for hand preference, but the successful children were significantly more often in the centre of the distribution of differences between the hands in skill than at the extremes, in both comparisons. The findings support the hypothesis prompted by the right shift theory of handedness (Annett, 1972, 1985) that there is natural variation for laterality and ability as expected for a genetic balanced polymorphism with Heterozygote Advantage. The findings cannot be attributed to slowness of the non-preferred hand at the extremes of the distribution, as might be predicted by an explanation in terms of developmental pathology.

Claudia Bank - One of the best experts on this subject based on the ideXlab platform.

  • conflict between Heterozygote Advantage and hybrid incompatibility in haplodiploids and sex chromosomes
    Molecular Ecology, 2018
    Co-Authors: Anahermina Ghenu, Alexandre Blanckaert, Roger K Butlin, Jonna Kulmuni, Claudia Bank
    Abstract:

    In many diploid species the sex chromosomes play a special role in mediating reproductive isolation. In haplodiploids, where females are diploid and males haploid, the whole genome behaves similarly to the X/Z chromosomes of diploids. Therefore, haplodiploid systems can serve as a model for the role of sex chromosomes in speciation and hybridization. A previously described population of Finnish Formica wood ants displays genome-wide signs of ploidally and sexually antagonistic selection resulting from hybridization. Here, hybrid females have increased survivorship but hybrid males are inviable. To understand how the unusual hybrid population may be maintained, we developed a mathematical model with hybrid incompatibility, female Heterozygote Advantage, recombination, and assortative mating. The rugged fitness landscape resulting from the co-occurrence of Heterozygote Advantage and hybrid incompatibility results in a sexual conflict in haplodiploids, which is caused by the ploidy difference. Thus, whereas Heterozygote Advantage always promotes long-term polymorphism in diploids, we find various outcomes in haplodiploids in which the population stabilizes either in favor of males, females, or via maximizing the number of introgressed individuals. We discuss these outcomes with respect to the potential long-term fate of the Finnish wood ant population, and provide approximations for the extension of the model to multiple incompatibilities. Moreover, we highlight the general implications of our results for speciation and hybridization in haplodiploids versus diploids, and how the described fitness relationships could contribute to the outstanding role of sex chromosomes as hotspots of sexual antagonism and genes involved in speciation. This article is protected by copyright. All rights reserved.

  • conflict between Heterozygote Advantage and hybrid incompatibility in haplodiploids and sex chromosomes
    bioRxiv, 2017
    Co-Authors: Anahermina Ghenu, Alexandre Blanckaert, Roger K Butlin, Jonna Kulmuni, Claudia Bank
    Abstract:

    In many diploid species the sex chromosomes play a special role in mediating reproductive isolation. In haplodiploids, where females are diploid and males haploid, the whole genome behaves similarly to the X/Z chromosomes of diploids. Therefore, haplodiploid systems can serve as a model for the role of sex chromosomes in speciation and hybridization. A previously described population of Finnish Formica wood ants displays genome-wide signs of ploidally and sexually antagonistic selection resulting from hybridization. Here, hybrid females have increased survivorship but hybrid males are inviable. To understand how the unusual hybrid population may be maintained, we developed a mathematical model with hybrid incompatibility, female Heterozygote Advantage, recombination, and assortative mating. The rugged fitness landscape resulting from the co-occurrence of Heterozygote Advantage and hybrid incompatibility results in a sexual conflict in haplodiploids, which is caused by the ploidy difference. Thus, whereas Heterozygote Advantage always promotes long-term polymorphism in diploids, we find various outcomes in haplodiploids in which the population stabilizes either in favor of males, females, or via maximizing the number of introgressed individuals. We discuss these outcomes with respect to the potential long-term fate of the Finnish wood ant population, and provide approximations for the extension of the model to multiple incompatibilities. Moreover, we highlight the general implications of our results for speciation and hybridization in haplodiploids versus diploids, and how the described fitness relationships could contribute to the outstanding role of sex chromosomes as hotspots of sexual antagonism and genes involved in speciation.

Dorian J Pritchard - One of the best experts on this subject based on the ideXlab platform.

Diamantis Sellis - One of the best experts on this subject based on the ideXlab platform.

  • Heterozygote Advantage is a common outcome of adaptation in saccharomyces cerevisiae
    Genetics, 2016
    Co-Authors: Diamantis Sellis, Daniel J Kvitek, Barbara L Dunn, Gavin Sherlock, Dmitri A Petrov
    Abstract:

    Adaptation in diploids is predicted to proceed via mutations that are at least partially dominant in fitness. Recently, we argued that many adaptive mutations might also be commonly overdominant in fitness. Natural (directional) selection acting on overdominant mutations should drive them into the population but then, instead of bringing them to fixation, should maintain them as balanced polymorphisms via Heterozygote Advantage. If true, this would make adaptive evolution in sexual diploids differ drastically from that of haploids. The validity of this prediction has not yet been tested experimentally. Here, we performed four replicate evolutionary experiments with diploid yeast populations (Saccharomyces cerevisiae) growing in glucose-limited continuous cultures. We sequenced 24 evolved clones and identified initial adaptive mutations in all four chemostats. The first adaptive mutations in all four chemostats were three copy number variations, all of which proved to be overdominant in fitness. The fact that fitness overdominant mutations were always the first step in independent adaptive walks supports the prediction that Heterozygote Advantage can arise as a common outcome of directional selection in diploids and demonstrates that overdominance of de novo adaptive mutations in diploids is not rare.

  • empirical evidence for Heterozygote Advantage in adapting diploid populations of saccharomyces cerevisiae
    bioRxiv, 2015
    Co-Authors: Diamantis Sellis, Daniel J Kvitek, Barbara L Dunn, Gavin Sherlock, Dmitri A Petrov
    Abstract:

    Adaptation in diploids is predicted to proceed via mutations that are at least partially dominant in fitness. Recently we argued that many adaptive mutations might also be commonly overdominant in fitness. Natural (directional) selection acting on overdominant mutations should drive them into the population but then, instead of bringing them to fixation, should maintain them as balanced polymorphisms via Heterozygote Advantage. If true, this would make adaptive evolution in sexual diploids differ drastically from that of haploids. Unfortunately, the validity of this prediction has not yet been tested experimentally. Here we performed 4 replicate evolutionary experiments with diploid yeast populations (Saccharomyces cerevisiae) growing in glucose-limited continuous cultures. We sequenced 24 evolved clones and identified initial adaptive mutations in all four chemostats. The first adaptive mutations in all four chemostats were three CNVs, all of which proved to be overdominant in fitness. The fact that fitness overdominant mutations were always the first step in independent adaptive walks strongly supports the prediction that Heterozygote Advantage can arise as a common outcome of directional selection in diploids and demonstrates that overdominance of de novo adaptive mutations in diploids is not rare.

  • Heterozygote Advantage as a natural consequence of adaptation in diploids
    Proceedings of the National Academy of Sciences of the United States of America, 2011
    Co-Authors: Diamantis Sellis, Benjamin J Callahan, Dmitri A Petrov, Philipp W Messer
    Abstract:

    Molecular adaptation is typically assumed to proceed by sequential fixation of beneficial mutations. In diploids, this picture presupposes that for most adaptive mutations, the homozygotes have a higher fitness than the Heterozygotes. Here, we show that contrary to this expectation, a substantial proportion of adaptive mutations should display Heterozygote Advantage. This feature of adaptation in diploids emerges naturally from the primary importance of the fitness of Heterozygotes for the invasion of new adaptive mutations. We formalize this result in the framework of Fisher's influential geometric model of adaptation. We find that in diploids, adaptation should often proceed through a succession of short-lived balanced states that maintain substantially higher levels of phenotypic and fitness variation in the population compared with classic adaptive walks. In fast-changing environments, this variation produces a diversity Advantage that allows diploids to remain better adapted compared with haploids despite the disAdvantage associated with the presence of unfit homozygotes. The short-lived balanced states arising during adaptive walks should be mostly invisible to current scans for long-term balancing selection. Instead, they should leave signatures of incomplete selective sweeps, which do appear to be common in many species. Our results also raise the possibility that balancing selection, as a natural consequence of frequent adaptation, might play a more prominent role among the forces maintaining genetic variation than is commonly recognized.