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Rafael A Irizarry - One of the best experts on this subject based on the ideXlab platform.

  • stochastic epigenetic variation as a driving force of development Evolutionary Adaptation and disease
    Proceedings of the National Academy of Sciences of the United States of America, 2010
    Co-Authors: Andrew P Feinberg, Rafael A Irizarry
    Abstract:

    Neo-Darwinian Evolutionary theory is based on exquisite selection of phenotypes caused by small genetic variations, which is the basis of quantitative trait contribution to phenotype and disease. Epigenetics is the study of nonsequence-based changes, such as DNA methylation, heritable during cell division. Previous attempts to incorporate epigenetics into Evolutionary thinking have focused on Lamarckian inheritance, that is, environmentally directed epigenetic changes. Here, we propose a new non-Lamarckian theory for a role of epigenetics in evolution. We suggest that genetic variants that do not change the mean phenotype could change the variability of phenotype; and this could be mediated epigenetically. This inherited stochastic variation model would provide a mechanism to explain an epigenetic role of developmental biology in selectable phenotypic variation, as well as the largely unexplained heritable genetic variation underlying common complex disease. We provide two experimental results as proof of principle. The first result is direct evidence for stochastic epigenetic variation, identifying highly variably DNA-methylated regions in mouse and human liver and mouse brain, associated with development and morphogenesis. The second is a heritable genetic mechanism for variable methylation, namely the loss or gain of CpG dinucleotides over Evolutionary time. Finally, we model genetically inherited stochastic variation in evolution, showing that it provides a powerful mechanism for Evolutionary Adaptation in changing environments that can be mediated epigenetically. These data suggest that genetically inherited propensity to phenotypic variability, even with no change in the mean phenotype, substantially increases fitness while increasing the disease susceptibility of a population with a changing environment.

  • colloquium paper stochastic epigenetic variation as a driving force of development Evolutionary Adaptation and disease
    Proceedings of the National Academy of Sciences of the United States of America, 2010
    Co-Authors: Andrew P Feinberg, Rafael A Irizarry
    Abstract:

    Neo-Darwinian Evolutionary theory is based on exquisite selection of phenotypes caused by small genetic variations, which is the basis of quantitative trait contribution to phenotype and disease. Epigenetics is the study of nonsequence-based changes, such as DNA methylation, heritable during cell division. Previous attempts to incorporate epigenetics into Evolutionary thinking have focused on Lamarckian inheritance, that is, environmentally directed epigenetic changes. Here, we propose a new non-Lamarckian theory for a role of epigenetics in evolution. We suggest that genetic variants that do not change the mean phenotype could change the variability of phenotype; and this could be mediated epigenetically. This inherited stochastic variation model would provide a mechanism to explain an epigenetic role of developmental biology in selectable phenotypic variation, as well as the largely unexplained heritable genetic variation underlying common complex disease. We provide two experimental results as proof of principle. The first result is direct evidence for stochastic epigenetic variation, identifying highly variably DNA-methylated regions in mouse and human liver and mouse brain, associated with development and morphogenesis. The second is a heritable genetic mechanism for variable methylation, namely the loss or gain of CpG dinucleotides over Evolutionary time. Finally, we model genetically inherited stochastic variation in evolution, showing that it provides a powerful mechanism for Evolutionary Adaptation in changing environments that can be mediated epigenetically. These data suggest that genetically inherited propensity to phenotypic variability, even with no change in the mean phenotype, substantially increases fitness while increasing the disease susceptibility of a population with a changing environment.

  • evolution in health and medicine sackler colloquium stochastic epigenetic variation as a driving force of development Evolutionary Adaptation and disease
    Proceedings of the National Academy of Sciences of the United States of America, 2009
    Co-Authors: Andrew P Feinberg, Rafael A Irizarry
    Abstract:

    Neo-Darwinian Evolutionary theory is based on exquisite selection of phenotypes caused by small genetic variations, which is the basis of quantitative trait contribution to phenotype and disease. Epigenetics is the study of nonsequence-based changes, such as DNA methylation, heritable during cell division. Previous attempts to incorporate epigenetics into Evolutionary thinking have focused on Lamarckian inheritance, that is, environmentally directed epigenetic changes. Here, we propose a new non-Lamarckian theory for a role of epigenetics in evolution. We suggest that genetic variants that do not change the mean phenotype could change the variability of phenotype; and this could be mediated epigenetically. This inherited stochastic variation model would provide a mechanism to explain an epigenetic role of developmental biology in selectable phenotypic variation, as well as the largely unexplained heritable genetic variation underlying common complex disease. We provide two experimental results as proof of principle. The first result is direct evidence for stochastic epigenetic variation, identifying highly variably DNA-methylated regions in mouse and human liver and mouse brain, associated with development and morphogenesis. The second is a heritable genetic mechanism for variable methylation, namely the loss or gain of CpG dinucleotides over Evolutionary time. Finally, we model genetically inherited stochastic variation in evolution, showing that it provides a powerful mechanism for Evolutionary Adaptation in changing environments that can be mediated epigenetically. These data suggest that genetically inherited propensity to phenotypic variability, even with no change in the mean phenotype, substantially increases fitness while increasing the disease susceptibility of a population with a changing environment.

Andreas Wagner - One of the best experts on this subject based on the ideXlab platform.

  • cryptic genetic variation promotes rapid Evolutionary Adaptation in an rna enzyme
    Nature, 2011
    Co-Authors: Eric J Hayden, Evandro Ferrada, Andreas Wagner
    Abstract:

    Some mutations, known as cryptic mutations, have no observable effect on an organism's phenotype unless combined with other mutations or environmental changes. As the originally cryptic variation can turn out to be beneficial in such new conditions, it has been proposed that it may facilitate Evolutionary Adaptation — or 'evolvability', but this has not been rigorously demonstrated experimentally because of the complexity of both natural genomes and environments. In a study of a simplified system in vitro — the catalytic activity of a single RNA enzyme — Andreas Wagner and colleagues demonstrate that a population that has accumulated more cryptic variation adapts more rapidly to a new chemical environment than a competing population with fewer variations. The existence of such a pre-Adaptation mechanism would have fundamental implications for animal and plant breeding, as well as for complex trait diseases in humans. Cryptic variation is caused by the robustness of phenotypes to mutations1. Cryptic variation has no effect on phenotypes in a given genetic or environmental background, but it can have effects after mutations or environmental change2,3,4,5. Because Evolutionary Adaptation by natural selection requires phenotypic variation, phenotypically revealed cryptic genetic variation may facilitate Evolutionary Adaptation6,7,8. This is possible if the cryptic variation happens to be pre-adapted, or “exapted”9, to a new environment, and is thus advantageous once revealed. However, this facilitating role for cryptic variation has not been proven, partly because most pertinent work focuses on complex phenotypes of whole organisms whose genetic basis is incompletely understood. Here we show that populations of RNA enzymes with accumulated cryptic variation adapt more rapidly to a new substrate than a population without cryptic variation. A detailed analysis of our evolving RNA populations in genotype space shows that cryptic variation allows a population to explore new genotypes that become adaptive only in a new environment. Our observations show that cryptic variation contains new genotypes pre-adapted to a changed environment. Our results highlight the positive role that robustness and epistasis can have in adaptive evolution10,11.

Andrew P Feinberg - One of the best experts on this subject based on the ideXlab platform.

  • stochastic epigenetic variation as a driving force of development Evolutionary Adaptation and disease
    Proceedings of the National Academy of Sciences of the United States of America, 2010
    Co-Authors: Andrew P Feinberg, Rafael A Irizarry
    Abstract:

    Neo-Darwinian Evolutionary theory is based on exquisite selection of phenotypes caused by small genetic variations, which is the basis of quantitative trait contribution to phenotype and disease. Epigenetics is the study of nonsequence-based changes, such as DNA methylation, heritable during cell division. Previous attempts to incorporate epigenetics into Evolutionary thinking have focused on Lamarckian inheritance, that is, environmentally directed epigenetic changes. Here, we propose a new non-Lamarckian theory for a role of epigenetics in evolution. We suggest that genetic variants that do not change the mean phenotype could change the variability of phenotype; and this could be mediated epigenetically. This inherited stochastic variation model would provide a mechanism to explain an epigenetic role of developmental biology in selectable phenotypic variation, as well as the largely unexplained heritable genetic variation underlying common complex disease. We provide two experimental results as proof of principle. The first result is direct evidence for stochastic epigenetic variation, identifying highly variably DNA-methylated regions in mouse and human liver and mouse brain, associated with development and morphogenesis. The second is a heritable genetic mechanism for variable methylation, namely the loss or gain of CpG dinucleotides over Evolutionary time. Finally, we model genetically inherited stochastic variation in evolution, showing that it provides a powerful mechanism for Evolutionary Adaptation in changing environments that can be mediated epigenetically. These data suggest that genetically inherited propensity to phenotypic variability, even with no change in the mean phenotype, substantially increases fitness while increasing the disease susceptibility of a population with a changing environment.

  • colloquium paper stochastic epigenetic variation as a driving force of development Evolutionary Adaptation and disease
    Proceedings of the National Academy of Sciences of the United States of America, 2010
    Co-Authors: Andrew P Feinberg, Rafael A Irizarry
    Abstract:

    Neo-Darwinian Evolutionary theory is based on exquisite selection of phenotypes caused by small genetic variations, which is the basis of quantitative trait contribution to phenotype and disease. Epigenetics is the study of nonsequence-based changes, such as DNA methylation, heritable during cell division. Previous attempts to incorporate epigenetics into Evolutionary thinking have focused on Lamarckian inheritance, that is, environmentally directed epigenetic changes. Here, we propose a new non-Lamarckian theory for a role of epigenetics in evolution. We suggest that genetic variants that do not change the mean phenotype could change the variability of phenotype; and this could be mediated epigenetically. This inherited stochastic variation model would provide a mechanism to explain an epigenetic role of developmental biology in selectable phenotypic variation, as well as the largely unexplained heritable genetic variation underlying common complex disease. We provide two experimental results as proof of principle. The first result is direct evidence for stochastic epigenetic variation, identifying highly variably DNA-methylated regions in mouse and human liver and mouse brain, associated with development and morphogenesis. The second is a heritable genetic mechanism for variable methylation, namely the loss or gain of CpG dinucleotides over Evolutionary time. Finally, we model genetically inherited stochastic variation in evolution, showing that it provides a powerful mechanism for Evolutionary Adaptation in changing environments that can be mediated epigenetically. These data suggest that genetically inherited propensity to phenotypic variability, even with no change in the mean phenotype, substantially increases fitness while increasing the disease susceptibility of a population with a changing environment.

  • evolution in health and medicine sackler colloquium stochastic epigenetic variation as a driving force of development Evolutionary Adaptation and disease
    Proceedings of the National Academy of Sciences of the United States of America, 2009
    Co-Authors: Andrew P Feinberg, Rafael A Irizarry
    Abstract:

    Neo-Darwinian Evolutionary theory is based on exquisite selection of phenotypes caused by small genetic variations, which is the basis of quantitative trait contribution to phenotype and disease. Epigenetics is the study of nonsequence-based changes, such as DNA methylation, heritable during cell division. Previous attempts to incorporate epigenetics into Evolutionary thinking have focused on Lamarckian inheritance, that is, environmentally directed epigenetic changes. Here, we propose a new non-Lamarckian theory for a role of epigenetics in evolution. We suggest that genetic variants that do not change the mean phenotype could change the variability of phenotype; and this could be mediated epigenetically. This inherited stochastic variation model would provide a mechanism to explain an epigenetic role of developmental biology in selectable phenotypic variation, as well as the largely unexplained heritable genetic variation underlying common complex disease. We provide two experimental results as proof of principle. The first result is direct evidence for stochastic epigenetic variation, identifying highly variably DNA-methylated regions in mouse and human liver and mouse brain, associated with development and morphogenesis. The second is a heritable genetic mechanism for variable methylation, namely the loss or gain of CpG dinucleotides over Evolutionary time. Finally, we model genetically inherited stochastic variation in evolution, showing that it provides a powerful mechanism for Evolutionary Adaptation in changing environments that can be mediated epigenetically. These data suggest that genetically inherited propensity to phenotypic variability, even with no change in the mean phenotype, substantially increases fitness while increasing the disease susceptibility of a population with a changing environment.

Markus Göker - One of the best experts on this subject based on the ideXlab platform.

  • Phylogenomics of Rhodobacteraceae reveals Evolutionary Adaptation to marine and non-marine habitats
    The ISME Journal, 2017
    Co-Authors: Meinhard Simon, Carmen Scheuner, Jan P. Meier-kolthoff, Thorsten Brinkhoff, Irene Wagner-döbler, Marcus Ulbrich, Hans-peter Klenk, Dietmar Schomburg, Jörn Petersen, Markus Göker
    Abstract:

    Marine Rhodobacteraceae ( Alphaproteobacteria ) are key players of biogeochemical cycling, comprise up to 30% of bacterial communities in pelagic environments and are often mutualists of eukaryotes. As ‘ Roseobacter clade’, these ‘roseobacters’ are assumed to be monophyletic, but non-marine Rhodobacteraceae have not yet been included in phylogenomic analyses. Therefore, we analysed 106 genome sequences, particularly emphasizing gene sampling and its effect on phylogenetic stability, and investigated relationships between marine versus non-marine habitat, Evolutionary origin and genomic Adaptations. Our analyses, providing no unequivocal evidence for the monophyly of roseobacters, indicate several shifts between marine and non-marine habitats that occurred independently and were accompanied by characteristic changes in genomic content of orthologs, enzymes and metabolic pathways. Non-marine Rhodobacteraceae gained high-affinity transporters to cope with much lower sulphate concentrations and lost genes related to the reduced sodium chloride and organohalogen concentrations in their habitats. Marine Rhodobacteraceae gained genes required for fucoidan desulphonation and synthesis of the plant hormone indole 3-acetic acid and the compatible solutes ectoin and carnitin. However, neither plasmid composition, even though typical for the family, nor the degree of oligotrophy shows a systematic difference between marine and non-marine Rhodobacteraceae . We suggest the operational term ‘ Roseobacter group’ for the marine Rhodobacteraceae strains.

  • Phylogenomics of Rhodobacteraceae reveals Evolutionary Adaptation to marine and non-marine habitats
    The ISME Journal, 2017
    Co-Authors: Meinhard Simon, Carmen Scheuner, Jan P. Meier-kolthoff, Thorsten Brinkhoff, Irene Wagner-döbler, Marcus Ulbrich, Hans-peter Klenk, Dietmar Schomburg, Jörn Petersen, Markus Göker
    Abstract:

    Phylogenomics of Rhodobacteraceae reveals Evolutionary Adaptation to marine and non-marine habitats

Meinhard Simon - One of the best experts on this subject based on the ideXlab platform.

  • Phylogenomics of Rhodobacteraceae reveals Evolutionary Adaptation to marine and non-marine habitats
    The ISME Journal, 2017
    Co-Authors: Meinhard Simon, Carmen Scheuner, Jan P. Meier-kolthoff, Thorsten Brinkhoff, Irene Wagner-döbler, Marcus Ulbrich, Hans-peter Klenk, Dietmar Schomburg, Jörn Petersen, Markus Göker
    Abstract:

    Marine Rhodobacteraceae ( Alphaproteobacteria ) are key players of biogeochemical cycling, comprise up to 30% of bacterial communities in pelagic environments and are often mutualists of eukaryotes. As ‘ Roseobacter clade’, these ‘roseobacters’ are assumed to be monophyletic, but non-marine Rhodobacteraceae have not yet been included in phylogenomic analyses. Therefore, we analysed 106 genome sequences, particularly emphasizing gene sampling and its effect on phylogenetic stability, and investigated relationships between marine versus non-marine habitat, Evolutionary origin and genomic Adaptations. Our analyses, providing no unequivocal evidence for the monophyly of roseobacters, indicate several shifts between marine and non-marine habitats that occurred independently and were accompanied by characteristic changes in genomic content of orthologs, enzymes and metabolic pathways. Non-marine Rhodobacteraceae gained high-affinity transporters to cope with much lower sulphate concentrations and lost genes related to the reduced sodium chloride and organohalogen concentrations in their habitats. Marine Rhodobacteraceae gained genes required for fucoidan desulphonation and synthesis of the plant hormone indole 3-acetic acid and the compatible solutes ectoin and carnitin. However, neither plasmid composition, even though typical for the family, nor the degree of oligotrophy shows a systematic difference between marine and non-marine Rhodobacteraceae . We suggest the operational term ‘ Roseobacter group’ for the marine Rhodobacteraceae strains.

  • Phylogenomics of Rhodobacteraceae reveals Evolutionary Adaptation to marine and non-marine habitats
    The ISME Journal, 2017
    Co-Authors: Meinhard Simon, Carmen Scheuner, Jan P. Meier-kolthoff, Thorsten Brinkhoff, Irene Wagner-döbler, Marcus Ulbrich, Hans-peter Klenk, Dietmar Schomburg, Jörn Petersen, Markus Göker
    Abstract:

    Phylogenomics of Rhodobacteraceae reveals Evolutionary Adaptation to marine and non-marine habitats