Dataset Information

Evolvability and single-genotype fluctuation in phenotypic properties: a simple heteropolymer model.

ABSTRACT: Experiment showed that the response of a genotype to mutation, i.e., the magnitude of mutational change in a phenotypic property, can be correlated with the extent of phenotypic fluctuation among genetic clones. To address a possible statistical mechanical basis for such phenomena at the protein level, we consider a simple hydrophobic-polar lattice protein-chain model with an exhaustive mapping between sequence (genotype) and conformational (phenotype) spaces. Using squared end-to-end distance, R(N)(2), as an example conformational property, we study how the thermal fluctuation of a sequence's R(N)(2) may be predictive of the changes in the Boltzmann average R(N)(2) caused by single-point mutations on that sequence. We found that sequences with the same ground-state (R(N)(2))(0) exhibit a funnel-like organization under conditions favorable to chain collapse or folding: fluctuation (standard deviation sigma) of R(N)(2) tends to increase with mutational distance from a prototype sequence whose R(N)(2) deviates little from its (R(N)(2))(0). In general, large mutational decreases in R(N)(2) or in sigma are only possible for some, though not all, sequences with large sigma values. This finding suggests that single-genotype phenotypic fluctuation is a necessary, though not sufficient, indicator of evolvability toward genotypes with less phenotypic fluctuations.

SUBMITTER: Chen T

PROVIDER: S-EPMC2877360 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Evolvability and single-genotype fluctuation in phenotypic properties: a simple heteropolymer model.

Chen Tao T Vernazobres David D Yomo Tetsuya T Bornberg-Bauer Erich E Chan Hue Sun HS

Biophysical journal 20100601 11

Experiment showed that the response of a genotype to mutation, i.e., the magnitude of mutational change in a phenotypic property, can be correlated with the extent of phenotypic fluctuation among genetic clones. To address a possible statistical mechanical basis for such phenomena at the protein level, we consider a simple hydrophobic-polar lattice protein-chain model with an exhaustive mapping between sequence (genotype) and conformational (phenotype) spaces. Using squared end-to-end distance, ...[more]

PMID: 20513392

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Project description:Robustness and evolvability are highly intertwined properties of biological systems. The relationship between these properties determines how biological systems are able to withstand mutations and show variation in response to them. Computational studies have explored the relationship between these two properties using neutral networks of RNA sequences (genotype) and their secondary structures (phenotype) as a model system. However, these studies have assumed every mutation to a sequence to be equally likely; the differences in the likelihood of the occurrence of various mutations, and the consequence of probabilistic nature of the mutations in such a system have previously been ignored. Associating probabilities to mutations essentially results in the weighting of genotype space. We here perform a comparative analysis of weighted and unweighted neutral networks of RNA sequences, and subsequently explore the relationship between robustness and evolvability. We show that assuming an equal likelihood for all mutations (as in an unweighted network), underestimates robustness and overestimates evolvability of a system. In spite of discarding this assumption, we observe that a negative correlation between sequence (genotype) robustness and sequence evolvability persists, and also that structure (phenotype) robustness promotes structure evolvability, as observed in earlier studies using unweighted networks. We also study the effects of base composition bias on robustness and evolvability. Particularly, we explore the association between robustness and evolvability in a sequence space that is AU-rich-sequences with an AU content of 80% or higher, compared to a normal (unbiased) sequence space. We find that evolvability of both sequences and structures in an AU-rich space is lesser compared to the normal space, and robustness higher. We also observe that AU-rich populations evolving on neutral networks of phenotypes, can access less phenotypic variation compared to normal populations evolving on neutral networks.

Dataset Information

Evolvability and single-genotype fluctuation in phenotypic properties: a simple heteropolymer model.

Publications

Evolvability and single-genotype fluctuation in phenotypic properties: a simple heteropolymer model.

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