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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2006-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC1762315?pdf=render |
| _version_ | 1818436295693697024 |
|---|---|
| author | Yuuki Hayashi Takuyo Aita Hitoshi Toyota Yuzuru Husimi Itaru Urabe Tetsuya Yomo |
| author_facet | Yuuki Hayashi Takuyo Aita Hitoshi Toyota Yuzuru Husimi Itaru Urabe Tetsuya Yomo |
| author_sort | Yuuki Hayashi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T17:06:31Z |
| format | Article |
| id | doaj.art-ca9e86822bc144e2b63aa2683639aa6c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T17:06:31Z |
| publishDate | 2006-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ca9e86822bc144e2b63aa2683639aa6c2022-12-21T22:53:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032006-01-011e9610.1371/journal.pone.0000096Experimental rugged fitness landscape in protein sequence space.Yuuki HayashiTakuyo AitaHitoshi ToyotaYuzuru HusimiItaru UrabeTetsuya YomoThe 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.http://europepmc.org/articles/PMC1762315?pdf=render |
| spellingShingle | Yuuki Hayashi Takuyo Aita Hitoshi Toyota Yuzuru Husimi Itaru Urabe Tetsuya Yomo Experimental rugged fitness landscape in protein sequence space. PLoS ONE |
| title | Experimental rugged fitness landscape in protein sequence space. |
| title_full | Experimental rugged fitness landscape in protein sequence space. |
| title_fullStr | Experimental rugged fitness landscape in protein sequence space. |
| title_full_unstemmed | Experimental rugged fitness landscape in protein sequence space. |
| title_short | Experimental rugged fitness landscape in protein sequence space. |
| title_sort | experimental rugged fitness landscape in protein sequence space |
| url | http://europepmc.org/articles/PMC1762315?pdf=render |
| work_keys_str_mv | AT yuukihayashi experimentalruggedfitnesslandscapeinproteinsequencespace AT takuyoaita experimentalruggedfitnesslandscapeinproteinsequencespace AT hitoshitoyota experimentalruggedfitnesslandscapeinproteinsequencespace AT yuzuruhusimi experimentalruggedfitnesslandscapeinproteinsequencespace AT itaruurabe experimentalruggedfitnesslandscapeinproteinsequencespace AT tetsuyayomo experimentalruggedfitnesslandscapeinproteinsequencespace |