Transgenerational inheritance: Models and mechanisms of non–DNA sequence–based inheritance 1
Advances in molecular biology in the second half of the 20th century firmly established DNA sequence as the molecular substrate of inheritance. It appears that biology is much richer: Many phenomena and mechanisms of nongenetic and/or non–DNA sequence–based inheritance have been described in a range of model organisms, challenging our perception of the well-established relationship between transmitted genotype and phenotype. How can we learn more about the mechanism and effects of this extended type of inheritance? A useful distinction is often made between intergenerational and transgenerational inheritance. In the former, the environment of the parent can directly affect germ cells of the offspring.
A number of heritable effects can be modulated by environmental influences. When considering environmentally induced effects, a particular emphasis has been put on nutrition and stress as inducers of nongenetic effects. For example, parental diet can affect the phenotype of the offspring. As shown in one recent study exploring metabolic outcomes in both male and female mice born to parents that consumed a high-fat diet (33). Early life stress is another example for which several rodent models have been reported (35–37). An emphasis on nutritional models in mice might be the consequence of evocative epidemiological studies in humans that suggest maternal and paternal inheritance of nutritional states (38, 39). Although in most of the examples mentioned above the mechanisms of inheritance are unlikely to be DNA sequence–based, with varying strength of evidence, the mode(s) of transmission of nongenetic effects remain to be discovered.
“…a complete understanding of non–DNA sequence–based heritable effects requires a number of components, and we do not currently have the complete picture for any natural example.”
“Many phenomena and mechanisms of nongenetic and/or non–DNA sequence–based inheritance have been described in a range of model organisms, challenging our perception of the well-established relationship between transmitted genotype and phenotype.”
The semiconservative mechanism of DNA replication (40) provides a clear paradigm of how genetic information is faithfully transmitted during each cell division in mitosis and meiosis. This paradigm is so powerful that great emphasis has been placed on replicative inheritance of other information. Due to the well-understood mechanisms associated with the propagation of epigenetic states such as DNA methylation, experiments analyzing epigenetic modifications to DNA and chromatin have proved popular in attempts to explain the heritable memory of environmental experience. In both cases, enzymes have been identified that can “read” a modification and replicate it locally on the newly synthesized strand (in the case of DNA) or can propagate it on newly assembled histones on chromatin (41).
1. Transgenerational inheritance: Models and mechanisms of non–DNA sequence–based inheritance | Science
Advances in molecular biology in the second half of the 20th century firmly established DNA sequence as the molecular substrate of inheritance. It appears that biology is much richer: Many phenomena and mechanisms of nongenetic and/or non–DNA sequence–based inheritance have been described in a range of model organisms, challenging our perception of the well-established relationship between transmitted genotype and phenotype. How can we learn more about the mechanism and effects of this extended type of inheritance? A useful distinction is often made between intergenerational and transgenerational inheritance. In the former, the environment of the parent can directly affect germ cells of the offspring.
A number of heritable effects can be modulated by environmental influences. When considering environmentally induced effects, a particular emphasis has been put on nutrition and stress as inducers of nongenetic effects. For example, parental diet can affect the phenotype of the offspring. As shown in one recent study exploring metabolic outcomes in both male and female mice born to parents that consumed a high-fat diet (33). Early life stress is another example for which several rodent models have been reported (35–37). An emphasis on nutritional models in mice might be the consequence of evocative epidemiological studies in humans that suggest maternal and paternal inheritance of nutritional states (38, 39). Although in most of the examples mentioned above the mechanisms of inheritance are unlikely to be DNA sequence–based, with varying strength of evidence, the mode(s) of transmission of nongenetic effects remain to be discovered.
“…a complete understanding of non–DNA sequence–based heritable effects requires a number of components, and we do not currently have the complete picture for any natural example.”
“Many phenomena and mechanisms of nongenetic and/or non–DNA sequence–based inheritance have been described in a range of model organisms, challenging our perception of the well-established relationship between transmitted genotype and phenotype.”
The semiconservative mechanism of DNA replication (40) provides a clear paradigm of how genetic information is faithfully transmitted during each cell division in mitosis and meiosis. This paradigm is so powerful that great emphasis has been placed on replicative inheritance of other information. Due to the well-understood mechanisms associated with the propagation of epigenetic states such as DNA methylation, experiments analyzing epigenetic modifications to DNA and chromatin have proved popular in attempts to explain the heritable memory of environmental experience. In both cases, enzymes have been identified that can “read” a modification and replicate it locally on the newly synthesized strand (in the case of DNA) or can propagate it on newly assembled histones on chromatin (41).
1. Transgenerational inheritance: Models and mechanisms of non–DNA sequence–based inheritance | Science
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