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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...

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Detalles Bibliográficos
Autores principales: Rasmussen, David A, Stadler, Tanja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
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.
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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
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