Divergence, recombination and retention of functionality during protein evolution
| Autor: | Randall W. Hall, Richard A. Goldstein, David D. Pollock, Yanlong O Xu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Protein Folding
lcsh:QH426-470 Population lcsh:Medicine Genomics Biology Proteomics Evolution Molecular 03 medical and health sciences Protein structure Drug Discovery evolution Genetics Humans education Molecular Biology Probability 030304 developmental biology Recombination Genetic Patterns of evolution 0303 health sciences education.field_of_study Models Genetic 030302 biochemistry & molecular biology lcsh:R Genetic Variation Proteins Protein superfamily recombination lcsh:Genetics Evolutionary biology Viral evolution lattice models Molecular Medicine Protein folding Primary Research divergence |
| Zdroj: | Human Genomics, Vol 2, Iss 3, Pp 158-167 (2005) Human Genomics |
| ISSN: | 1479-7364 |
| Popis: | We have only a vague idea of precisely how protein sequences evolve in the context of protein structure and function. This is primarily because structural and functional contexts are not easily predictable from the primary sequence, and evaluating patterns of evolution at individual residue positions is also difficult. As a result of increasing biodiversity in genomics studies, progress is being made in detecting context-dependent variation in substitution processes, but it remains unclear exactly what context-dependent patterns we should be looking for. To address this, we have been simulating protein evolution in the context of structure and function using lattice models of proteins and ligands (or substrates). These simulations include thermodynamic features of protein stability and population dynamics. We refer to this approach as 'ab initio evolution' to emphasise the fact that the equilibrium details of fitness distributions arise from the physical principles of the system and not from any preconceived notions or arbitrary mathematical distributions. Here, we present results on the retention of functionality in homologous recombinants following population divergence. A central result is that protein structure characteristics can strongly influence recombinant functionality. Exceptional structures with many sequence options evolve quickly and tend to retain functionality -- even in highly diverged recombinants. By contrast, the more common structures with fewer sequence options evolve more slowly, but the fitness of recombinants drops off rapidly as homologous proteins diverge. These results have implications for understanding viral evolution, speciation and directed evolutionary experiments. Our analysis of the divergence process can also guide improved methods for accurately approximating folding probabilities in more complex but realistic systems. |
| Databáze: | OpenAIRE |
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