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A Practical Guide to Phylogenetics for Nonexperts
Published on: February 5, 2014
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A Practical Guide to Estimating the Heritability of Pathogen Traits
Venelin Mitov1,2, Tanja Stadler1,2
1Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Molecular Biology and Evolution
|January 13, 2018
Summary
Estimating pathogen heritability (H2) is challenging due to within-host evolution. A new model, POUMM, accurately quantifies HIV-virulence heritability, revealing ~20% variation is due to viral genetics.
Area of Science:
- Evolutionary biology
- Quantitative genetics
- Virology
Background:
- Pathogen virulence varies significantly among hosts.
- Estimating the genetic basis of this variation (heritability, H2) is crucial but challenging.
- Previous methods underestimated HIV-virulence heritability due to lifecycle differences and within-host evolution.
Purpose of the Study:
- To identify limitations in current quantitative genetics methods for pathogens.
- To develop and validate a new model for accurately estimating pathogen heritability.
- To quantify the heritability of HIV-virulence.
Main Methods:
- Phylogenetic analysis of 8,483 HIV patients.
- Comparison of phylogenetic mixed model (PMM) with a phylogenetic Ornstein-Uhlenbeck model (POUMM).
- Simulations to assess model performance under varying evolutionary scenarios.
- Cross-validation using ANOVA on closest phylogenetic pairs.
Main Results:
- Phenotypic correlation between transmission partners decays with within-host viral evolution.
- POUMM outperforms PMM in capturing this correlation and estimating heritability.
- POUMM accurately estimates heritability even without strong selection.
- Estimated HIV-virulence heritability (H2) is approximately 0.2 (~20%) across diverse patient data.
Conclusions:
- Standard quantitative genetics models underestimate pathogen heritability.
- Within-host evolution reduces resemblance between transmission partners, a factor POUMM accounts for.
- Viral genetic variation explains approximately 20% of the variation in HIV-virulence.
Keywords:
ANOVAHIVOrnstein–Uhlenbeckdonor–recipient regressionphylogenetic mixed modelset-point viral load (spVL)More Related Videos
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