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Does the central dogma still stand?

Koonin EV - Biol. Direct (2012)

Bottom Line: The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation.The epigenetic variation precedes and facilitates genetic adaptation through a general 'look-ahead effect' of phenotypic mutations.This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. koonin@ncbi.nlm.nih.gov

ABSTRACT
Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation. The epigenetic variation precedes and facilitates genetic adaptation through a general 'look-ahead effect' of phenotypic mutations. This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits.

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The general look-ahead effect: information flow from protein sequence to genome via assimilation of epigenetic variation.
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Figure 3: The general look-ahead effect: information flow from protein sequence to genome via assimilation of epigenetic variation.

Mentions: In general terms, what prions do, is extremely simple: they buy time for the cell to accumulate the beneficial combination of mutations through recombination and possibly new mutations as well. This appears to be a specific manifestation of a most general phenomenon (Figure 3). Any phenotypic variation in protein sequence or structure, such as spontaneous error of transcription, splicing, RNA editing or translation, capacitation of hidden genetic or phenotypic variability or protein misfolding, that is beneficial either on its own or combined with another mutation (i.e. depending on the genetic background) can potentially become hereditary through the ‘look-ahead effect’ [51], i.e. by allowing the organism time to generate the required genotype by recombination or to generate the required mutation(s) de novo. In other words, a phenotypic and a genomic mutation complement each other to produce a transient beneficial phenotype (Figure 3). The rate of amino acid misincorporation is orders of magnitude greater than the replication error rate, so any cell contains numerous variant proteins [52,53]. These phenotypic mutations might underlie evolution of complex traits that require more than one mutation (a simplest example of a potentially beneficial structural feature of proteins that requires two mutations is a new disulfide bond). Direct experimental study of the look-ahead effect is still lacking but population-genetic models indicate that phenotypic mutations can be sufficient for alleles carrying only one mutation required for a trait dependent on two mutations to spread in a population provided the selective advantage of the combination of two mutations is high enough [51]. Furthermore, the error rate of translation increases under stress [54,55] with the implication that the look-ahead effect could be particularly important to generate stress-resistant phenotypes – and eventually genotypes. Moreover, agents that specifically induce mistranslation, such as streptomycin, also cause a mutator phenotype via mistranslation-induced mutagenesis [56], directly demonstrating the coupling of epigenetic and genetic variation [57]. The look-ahead effect can be similarly potentiated by errors of transcription, splicing or RNA editing. Although in these cases, the actual change occurs in the RNA sequence, the net result is the same: information potentially can be transferred from a protein sequence back to the genome.


Does the central dogma still stand?

Koonin EV - Biol. Direct (2012)

The general look-ahead effect: information flow from protein sequence to genome via assimilation of epigenetic variation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472225&req=5

Figure 3: The general look-ahead effect: information flow from protein sequence to genome via assimilation of epigenetic variation.
Mentions: In general terms, what prions do, is extremely simple: they buy time for the cell to accumulate the beneficial combination of mutations through recombination and possibly new mutations as well. This appears to be a specific manifestation of a most general phenomenon (Figure 3). Any phenotypic variation in protein sequence or structure, such as spontaneous error of transcription, splicing, RNA editing or translation, capacitation of hidden genetic or phenotypic variability or protein misfolding, that is beneficial either on its own or combined with another mutation (i.e. depending on the genetic background) can potentially become hereditary through the ‘look-ahead effect’ [51], i.e. by allowing the organism time to generate the required genotype by recombination or to generate the required mutation(s) de novo. In other words, a phenotypic and a genomic mutation complement each other to produce a transient beneficial phenotype (Figure 3). The rate of amino acid misincorporation is orders of magnitude greater than the replication error rate, so any cell contains numerous variant proteins [52,53]. These phenotypic mutations might underlie evolution of complex traits that require more than one mutation (a simplest example of a potentially beneficial structural feature of proteins that requires two mutations is a new disulfide bond). Direct experimental study of the look-ahead effect is still lacking but population-genetic models indicate that phenotypic mutations can be sufficient for alleles carrying only one mutation required for a trait dependent on two mutations to spread in a population provided the selective advantage of the combination of two mutations is high enough [51]. Furthermore, the error rate of translation increases under stress [54,55] with the implication that the look-ahead effect could be particularly important to generate stress-resistant phenotypes – and eventually genotypes. Moreover, agents that specifically induce mistranslation, such as streptomycin, also cause a mutator phenotype via mistranslation-induced mutagenesis [56], directly demonstrating the coupling of epigenetic and genetic variation [57]. The look-ahead effect can be similarly potentiated by errors of transcription, splicing or RNA editing. Although in these cases, the actual change occurs in the RNA sequence, the net result is the same: information potentially can be transferred from a protein sequence back to the genome.

Bottom Line: The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation.The epigenetic variation precedes and facilitates genetic adaptation through a general 'look-ahead effect' of phenotypic mutations.This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. koonin@ncbi.nlm.nih.gov

ABSTRACT
Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation. The epigenetic variation precedes and facilitates genetic adaptation through a general 'look-ahead effect' of phenotypic mutations. This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits.

Show MeSH