Genotype to phenotype mapping and the fitness landscape of the E. coli lac promoter.
Genotype-to-phenotype maps and the related fitness landscapes that include epistatic interactions are difficult to measure because of their high dimensional structure. Here we construct such a map using the recently collected corpora of high-throughput sequence data from the 75 base pairs long mutag...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3641078?pdf=render |
| _version_ | 1819024597543026688 |
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| author | Jakub Otwinowski Ilya Nemenman |
| author_facet | Jakub Otwinowski Ilya Nemenman |
| author_sort | Jakub Otwinowski |
| collection | DOAJ |
| description | Genotype-to-phenotype maps and the related fitness landscapes that include epistatic interactions are difficult to measure because of their high dimensional structure. Here we construct such a map using the recently collected corpora of high-throughput sequence data from the 75 base pairs long mutagenized E. coli lac promoter region, where each sequence is associated with its phenotype, the induced transcriptional activity measured by a fluorescent reporter. We find that the additive (non-epistatic) contributions of individual mutations account for about two-thirds of the explainable phenotype variance, while pairwise epistasis explains about 7% of the variance for the full mutagenized sequence and about 15% for the subsequence associated with protein binding sites. Surprisingly, there is no evidence for third order epistatic contributions, and our inferred fitness landscape is essentially single peaked, with a small amount of antagonistic epistasis. There is a significant selective pressure on the wild type, which we deduce to be multi-objective optimal for gene expression in environments with different nutrient sources. We identify transcription factor (CRP) and RNA polymerase binding sites in the promotor region and their interactions without difficult optimization steps. In particular, we observe evidence for previously unexplored genetic regulatory mechanisms, possibly kinetic in nature. We conclude with a cautionary note that inferred properties of fitness landscapes may be severely influenced by biases in the sequence data. |
| first_indexed | 2024-12-21T04:57:19Z |
| format | Article |
| id | doaj.art-022c865a42d24bbcbbf487079ff81ced |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T04:57:19Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-022c865a42d24bbcbbf487079ff81ced2022-12-21T19:15:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6157010.1371/journal.pone.0061570Genotype to phenotype mapping and the fitness landscape of the E. coli lac promoter.Jakub OtwinowskiIlya NemenmanGenotype-to-phenotype maps and the related fitness landscapes that include epistatic interactions are difficult to measure because of their high dimensional structure. Here we construct such a map using the recently collected corpora of high-throughput sequence data from the 75 base pairs long mutagenized E. coli lac promoter region, where each sequence is associated with its phenotype, the induced transcriptional activity measured by a fluorescent reporter. We find that the additive (non-epistatic) contributions of individual mutations account for about two-thirds of the explainable phenotype variance, while pairwise epistasis explains about 7% of the variance for the full mutagenized sequence and about 15% for the subsequence associated with protein binding sites. Surprisingly, there is no evidence for third order epistatic contributions, and our inferred fitness landscape is essentially single peaked, with a small amount of antagonistic epistasis. There is a significant selective pressure on the wild type, which we deduce to be multi-objective optimal for gene expression in environments with different nutrient sources. We identify transcription factor (CRP) and RNA polymerase binding sites in the promotor region and their interactions without difficult optimization steps. In particular, we observe evidence for previously unexplored genetic regulatory mechanisms, possibly kinetic in nature. We conclude with a cautionary note that inferred properties of fitness landscapes may be severely influenced by biases in the sequence data.http://europepmc.org/articles/PMC3641078?pdf=render |
| spellingShingle | Jakub Otwinowski Ilya Nemenman Genotype to phenotype mapping and the fitness landscape of the E. coli lac promoter. PLoS ONE |
| title | Genotype to phenotype mapping and the fitness landscape of the E. coli lac promoter. |
| title_full | Genotype to phenotype mapping and the fitness landscape of the E. coli lac promoter. |
| title_fullStr | Genotype to phenotype mapping and the fitness landscape of the E. coli lac promoter. |
| title_full_unstemmed | Genotype to phenotype mapping and the fitness landscape of the E. coli lac promoter. |
| title_short | Genotype to phenotype mapping and the fitness landscape of the E. coli lac promoter. |
| title_sort | genotype to phenotype mapping and the fitness landscape of the e coli lac promoter |
| url | http://europepmc.org/articles/PMC3641078?pdf=render |
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