Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models

Area of Science:

• Evolutionary biology
• Phylogenetics
• Molecular evolution

Background:

• Mutations influence lineage fitness and phylogenetic branching.
• Existing birth-death models track lineage fitness based on single character states.
• Phylogenetic models traditionally do not account for mutation feedback on tree structure.

Purpose of the Study:

• To extend multi-type birth-death models to track sequence evolution at multiple sites.
• To develop a computationally tractable method for estimating lineage and mutation fitness from phylogenies.
• To assess population-level fitness effects of mutations in viruses like Ebola and influenza.

Main Methods:

• Probabilistic tracking of lineage genotype and fitness in an approximate manner.
• Extension of multi-type birth-death models to accommodate multi-site sequence evolution.
• Application to phylogenies of Ebola and influenza viruses.

Main Results:

• Accurate estimation of lineage fitness and site-specific mutational fitness effects from phylogenies.
• Successful application to Ebola and influenza virus datasets.
• Comparison of estimated fitness effects with in vitro measurements.

Conclusions:

• The developed model accurately estimates mutation fitness effects from phylogenetic data.
• This approach provides insights into population-level fitness of viral mutations.
• The method is applicable to real-world viral evolution studies, such as for Ebola and influenza.