The intrinsic dimension of protein sequence evolution.
It is well known that, in order to preserve its structure and function, a protein cannot change its sequence at random, but only by mutations occurring preferentially at specific locations. We here investigate quantitatively the amount of variability that is allowed in protein sequence evolution, by...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-04-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC6472826?pdf=render |
| _version_ | 1818313293169688576 |
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| author | Elena Facco Andrea Pagnani Elena Tea Russo Alessandro Laio |
| author_facet | Elena Facco Andrea Pagnani Elena Tea Russo Alessandro Laio |
| author_sort | Elena Facco |
| collection | DOAJ |
| description | It is well known that, in order to preserve its structure and function, a protein cannot change its sequence at random, but only by mutations occurring preferentially at specific locations. We here investigate quantitatively the amount of variability that is allowed in protein sequence evolution, by computing the intrinsic dimension (ID) of the sequences belonging to a selection of protein families. The ID is a measure of the number of independent directions that evolution can take starting from a given sequence. We find that the ID is practically constant for sequences belonging to the same family, and moreover it is very similar in different families, with values ranging between 6 and 12. These values are significantly smaller than the raw number of amino acids, confirming the importance of correlations between mutations in different sites. However, we demonstrate that correlations are not sufficient to explain the small value of the ID we observe in protein families. Indeed, we show that the ID of a set of protein sequences generated by maximum entropy models, an approach in which correlations are accounted for, is typically significantly larger than the value observed in natural protein families. We further prove that a critical factor to reproduce the natural ID is to take into consideration the phylogeny of sequences. |
| first_indexed | 2024-12-13T08:31:26Z |
| format | Article |
| id | doaj.art-6d7d70e742734e51af10aaa23ef3e660 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-13T08:31:26Z |
| publishDate | 2019-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-6d7d70e742734e51af10aaa23ef3e6602022-12-21T23:53:45ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582019-04-01154e100676710.1371/journal.pcbi.1006767The intrinsic dimension of protein sequence evolution.Elena FaccoAndrea PagnaniElena Tea RussoAlessandro LaioIt is well known that, in order to preserve its structure and function, a protein cannot change its sequence at random, but only by mutations occurring preferentially at specific locations. We here investigate quantitatively the amount of variability that is allowed in protein sequence evolution, by computing the intrinsic dimension (ID) of the sequences belonging to a selection of protein families. The ID is a measure of the number of independent directions that evolution can take starting from a given sequence. We find that the ID is practically constant for sequences belonging to the same family, and moreover it is very similar in different families, with values ranging between 6 and 12. These values are significantly smaller than the raw number of amino acids, confirming the importance of correlations between mutations in different sites. However, we demonstrate that correlations are not sufficient to explain the small value of the ID we observe in protein families. Indeed, we show that the ID of a set of protein sequences generated by maximum entropy models, an approach in which correlations are accounted for, is typically significantly larger than the value observed in natural protein families. We further prove that a critical factor to reproduce the natural ID is to take into consideration the phylogeny of sequences.http://europepmc.org/articles/PMC6472826?pdf=render |
| spellingShingle | Elena Facco Andrea Pagnani Elena Tea Russo Alessandro Laio The intrinsic dimension of protein sequence evolution. PLoS Computational Biology |
| title | The intrinsic dimension of protein sequence evolution. |
| title_full | The intrinsic dimension of protein sequence evolution. |
| title_fullStr | The intrinsic dimension of protein sequence evolution. |
| title_full_unstemmed | The intrinsic dimension of protein sequence evolution. |
| title_short | The intrinsic dimension of protein sequence evolution. |
| title_sort | intrinsic dimension of protein sequence evolution |
| url | http://europepmc.org/articles/PMC6472826?pdf=render |
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