Publication

Inferring the age and strength of mutations evolving under positive selection

Nicky Louise Ormond
2017
EPFL thesis
Abstract

A fundamental goal of population genetics is to determine and quantify the interplay of mutation, natural selection, genetic drift and migration in shaping allelic frequency changes that underpin evolution-ary change. In this dissertation, I present computational, empirical and experimental approaches to address this goal. In the first chapter, I develop an approximate Bayesian computation (ABC) approach that co-estimates the selection strength and age of fixed beneficial mutations in single populations, by integrating a range of existing diversity, site frequency spectrum, haplotype and linkage disequilibrium based summary statistics. This approach is then extended to models of selection on standing variation in order to co-infer the frequency at which positive selection began to act upon the mutation. In the second chapter, I apply this method to an empirical study of convergent adaptation of blanched dorsal phenotypes in two lizard species to the newly formed White Sands system of New Mexico. Estimates of the age of the beneficial mutations underpinning the evolution of cryptic coloration are younger than the related geological shift and support a model of adaptation from de novo mutation. In the third chapter, I analyze the experimental evolution of H1N1 influenza virus populations under a combined protocol of two drugs with different modes of action: oseltamivir and favipiravir. Results indicate a complex interplay of mutation, selection and genetic drift, where selective sweeps around oseltamivir resistance mutations hitchhike deleterious mutations owing to the mutagenic effect of favipiravir to fixation. This effect reduces viral fitness and ac-celerates extinction via Muller’s ratchet, but at the risk of spreading both established and newly emerging oseltamivir resistance mutations.

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Related concepts (43)
Natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Charles Darwin popularised the term "natural selection", contrasting it with artificial selection, which is intentional, whereas natural selection is not. Variation exists within all populations of organisms. This occurs partly because random mutations arise in the genome of an individual organism, and their offspring can inherit such mutations.
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication (translesion synthesis).
Mutation rate
In genetics, the mutation rate is the frequency of new mutations in a single gene or organism over time. Mutation rates are not constant and are not limited to a single type of mutation; there are many different types of mutations. Mutation rates are given for specific classes of mutations. Point mutations are a class of mutations which are changes to a single base. Missense and Nonsense mutations are two subtypes of point mutations.
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