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Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models
Beneficial and deleterious mutations cause the fitness of lineages to vary across a phylogeny and thereby shape its branching structure. While standard phylogenetic models do not allow mutations to feedback and shape trees, birth-death models can account for this feedback by letting the fitness of l...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715349/ https://www.ncbi.nlm.nih.gov/pubmed/31411558 http://dx.doi.org/10.7554/eLife.45562 |
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author | Rasmussen, David A Stadler, Tanja |
author_facet | Rasmussen, David A Stadler, Tanja |
author_sort | Rasmussen, David A |
collection | PubMed |
description | Beneficial and deleterious mutations cause the fitness of lineages to vary across a phylogeny and thereby shape its branching structure. While standard phylogenetic models do not allow mutations to feedback and shape trees, birth-death models can account for this feedback by letting the fitness of lineages depend on their type. To date, these multi-type birth-death models have only been applied to cases where a lineage’s fitness is determined by a single character state. We extend these models to track sequence evolution at multiple sites. This approach remains computationally tractable by tracking the genotype and fitness of lineages probabilistically in an approximate manner. Although approximate, we show that we can accurately estimate the fitness of lineages and site-specific mutational fitness effects from phylogenies. We apply this approach to estimate the population-level fitness effects of mutations in Ebola and influenza virus, and compare our estimates with in vitro fitness measurements for these mutations. |
format | Online Article Text |
id | pubmed-6715349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-67153492019-08-30 Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models Rasmussen, David A Stadler, Tanja eLife Evolutionary Biology Beneficial and deleterious mutations cause the fitness of lineages to vary across a phylogeny and thereby shape its branching structure. While standard phylogenetic models do not allow mutations to feedback and shape trees, birth-death models can account for this feedback by letting the fitness of lineages depend on their type. To date, these multi-type birth-death models have only been applied to cases where a lineage’s fitness is determined by a single character state. We extend these models to track sequence evolution at multiple sites. This approach remains computationally tractable by tracking the genotype and fitness of lineages probabilistically in an approximate manner. Although approximate, we show that we can accurately estimate the fitness of lineages and site-specific mutational fitness effects from phylogenies. We apply this approach to estimate the population-level fitness effects of mutations in Ebola and influenza virus, and compare our estimates with in vitro fitness measurements for these mutations. eLife Sciences Publications, Ltd 2019-08-15 /pmc/articles/PMC6715349/ /pubmed/31411558 http://dx.doi.org/10.7554/eLife.45562 Text en © 2019, Rasmussen and Stadler http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Evolutionary Biology Rasmussen, David A Stadler, Tanja Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models |
title | Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models |
title_full | Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models |
title_fullStr | Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models |
title_full_unstemmed | Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models |
title_short | Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models |
title_sort | coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models |
topic | Evolutionary Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715349/ https://www.ncbi.nlm.nih.gov/pubmed/31411558 http://dx.doi.org/10.7554/eLife.45562 |
work_keys_str_mv | AT rasmussendavida couplingadaptivemolecularevolutiontophylodynamicsusingfitnessdependentbirthdeathmodels AT stadlertanja couplingadaptivemolecularevolutiontophylodynamicsusingfitnessdependentbirthdeathmodels |