Experimental rugged fitness landscape in protein sequence space
The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat...
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| description | The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12-130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7x10(4)-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. Based on the results of these analyses, k was estimated to be 18-24. According to the estimated parameters, the landscape was plotted as a smooth surface up to a relative fitness of 0.4 of the global peak, whereas the landscape had a highly rugged surface with many local peaks above this relative fitness value. Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region. |
| doi_str_mv | 10.1371/journal.pone.0000096 |
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To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12-130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7x10(4)-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. 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Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0000096</identifier><identifier>PMID: 17183728</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amino Acid Sequence ; Amino acids ; Analysis ; Bacteriophage M13 - genetics ; Bacteriophage M13 - pathogenicity ; Biophysics ; Biopolymers ; Capsid Proteins - genetics ; Cloning ; Coat protein ; Deoxyribonucleic acid ; Directed Molecular Evolution ; DNA ; DNA polymerase ; E coli ; Escherichia coli - virology ; Evolution ; Evolution, Molecular ; Evolutionary Biology ; Fitness ; Health aspects ; Infectivity ; Laboratories ; Landscape ; Materials science ; Models, Genetic ; Molecular Biology ; Molecular evolution ; Molecular Sequence Data ; Mutation ; Novellas ; Parameter estimation ; Phages ; Polymerase chain reaction ; Polypeptides ; Proteins ; Proteins - genetics ; Reproductive fitness ; Vectors (Biology)</subject><ispartof>PloS one, 2006-12, Vol.1 (1), p.e96-e96</ispartof><rights>COPYRIGHT 2006 Public Library of Science</rights><rights>2006 Hayashi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Hayashi et al. 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-34e8e5377aa33fbf345cc68d4d8e7d8b74a2f3df616f35c78a037ad1a3ec29aa3</citedby><cites>FETCH-LOGICAL-c758t-34e8e5377aa33fbf345cc68d4d8e7d8b74a2f3df616f35c78a037ad1a3ec29aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762315/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762315/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17183728$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Rutherford, Suzannah</contributor><creatorcontrib>Hayashi, Yuuki</creatorcontrib><creatorcontrib>Aita, Takuyo</creatorcontrib><creatorcontrib>Toyota, Hitoshi</creatorcontrib><creatorcontrib>Husimi, Yuzuru</creatorcontrib><creatorcontrib>Urabe, Itaru</creatorcontrib><creatorcontrib>Yomo, Tetsuya</creatorcontrib><title>Experimental rugged fitness landscape in protein sequence space</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12-130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7x10(4)-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. 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Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region.</description><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Analysis</subject><subject>Bacteriophage M13 - genetics</subject><subject>Bacteriophage M13 - pathogenicity</subject><subject>Biophysics</subject><subject>Biopolymers</subject><subject>Capsid Proteins - genetics</subject><subject>Cloning</subject><subject>Coat protein</subject><subject>Deoxyribonucleic acid</subject><subject>Directed Molecular Evolution</subject><subject>DNA</subject><subject>DNA polymerase</subject><subject>E coli</subject><subject>Escherichia coli - virology</subject><subject>Evolution</subject><subject>Evolution, Molecular</subject><subject>Evolutionary Biology</subject><subject>Fitness</subject><subject>Health aspects</subject><subject>Infectivity</subject><subject>Laboratories</subject><subject>Landscape</subject><subject>Materials science</subject><subject>Models, Genetic</subject><subject>Molecular Biology</subject><subject>Molecular evolution</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Novellas</subject><subject>Parameter estimation</subject><subject>Phages</subject><subject>Polymerase chain reaction</subject><subject>Polypeptides</subject><subject>Proteins</subject><subject>Proteins - 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To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12-130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7x10(4)-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. Based on the results of these analyses, k was estimated to be 18-24. According to the estimated parameters, the landscape was plotted as a smooth surface up to a relative fitness of 0.4 of the global peak, whereas the landscape had a highly rugged surface with many local peaks above this relative fitness value. Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>17183728</pmid><doi>10.1371/journal.pone.0000096</doi><tpages>e96</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Amino acids Analysis Bacteriophage M13 - genetics Bacteriophage M13 - pathogenicity Biophysics Biopolymers Capsid Proteins - genetics Cloning Coat protein Deoxyribonucleic acid Directed Molecular Evolution DNA DNA polymerase E coli Escherichia coli - virology Evolution Evolution, Molecular Evolutionary Biology Fitness Health aspects Infectivity Laboratories Landscape Materials science Models, Genetic Molecular Biology Molecular evolution Molecular Sequence Data Mutation Novellas Parameter estimation Phages Polymerase chain reaction Polypeptides Proteins Proteins - genetics Reproductive fitness Vectors (Biology) |
| title | Experimental rugged fitness landscape in protein sequence space |
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