dorsal/arxiv
View SchemaThermodynamics of Neutral Protein Evolution
| Authors | Jesse D Bloom, Alpan Raval, Claus O Wilke |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0605041 |
| URL | https://arxiv.org/abs/q-bio/0605041 |
| DOI | 10.1534/genetics.106.061754 |
| Journal | Genetics 175:1-12 (January 2007) |
Abstract
Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of genetic change, and forms the basis for the molecular clock. Here we present a mathematical theory that predicts the number of accumulated mutations, the index of dispersion, and the distribution of stabilities in an evolving protein population from knowledge of the stability effects (ddG values) for single mutations. Our theory quantitatively describes how neutral evolution leads to marginally stable proteins, and provides formulae for calculating how fluctuations in stability cause an overdispersion of the molecular clock. It also shows that the structural influences on the rate of sequence evolution that have been observed in earlier simulations can be calculated using only the single-mutation ddG values. We consider both the case when the product of the population size and mutation rate is small and the case when this product is large, and show that in the latter case proteins evolve excess mutational robustness that is manifested by extra stability and increases the rate of sequence evolution. Our basic method is to treat protein evolution as a Markov process constrained by a minimal requirement for stable folding, enabling an evolutionary description of the proteins solely in terms of the experimentally measureable ddG values. All of our theoretical predictions are confirmed by simulations with model lattice proteins. Our work provides a mathematical foundation for understanding how protein biophysics helps shape the process of evolution.
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"abstract": "Naturally evolving proteins gradually accumulate mutations while continuing\nto fold to thermodynamically stable native structures. This process of neutral\nprotein evolution is an important mode of genetic change, and forms the basis\nfor the molecular clock. Here we present a mathematical theory that predicts\nthe number of accumulated mutations, the index of dispersion, and the\ndistribution of stabilities in an evolving protein population from knowledge of\nthe stability effects (ddG values) for single mutations. Our theory\nquantitatively describes how neutral evolution leads to marginally stable\nproteins, and provides formulae for calculating how fluctuations in stability\ncause an overdispersion of the molecular clock. It also shows that the\nstructural influences on the rate of sequence evolution that have been observed\nin earlier simulations can be calculated using only the single-mutation ddG\nvalues. We consider both the case when the product of the population size and\nmutation rate is small and the case when this product is large, and show that\nin the latter case proteins evolve excess mutational robustness that is\nmanifested by extra stability and increases the rate of sequence evolution. Our\nbasic method is to treat protein evolution as a Markov process constrained by a\nminimal requirement for stable folding, enabling an evolutionary description of\nthe proteins solely in terms of the experimentally measureable ddG values. All\nof our theoretical predictions are confirmed by simulations with model lattice\nproteins. Our work provides a mathematical foundation for understanding how\nprotein biophysics helps shape the process of evolution.",
"arxiv_id": "q-bio/0605041",
"authors": [
"Jesse D Bloom",
"Alpan Raval",
"Claus O Wilke"
],
"categories": [
"q-bio.PE",
"q-bio.BM"
],
"doi": "10.1534/genetics.106.061754",
"journal_ref": "Genetics 175:1-12 (January 2007)",
"title": "Thermodynamics of Neutral Protein Evolution",
"url": "https://arxiv.org/abs/q-bio/0605041"
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