Selective Strolls: Fixation and Extinction in Diploids Are Slower for Weakly Selected Mutations Than for Neutral Ones

Abstract

In finite populations, an allele disappears or reaches fixation due to two main forces, selection and drift. Selection is generally thought to accelerate the process: a selected mutation will reach fixation faster than a neutral one, and a disadvantageous one will quickly disappear from the population. We show that even in simple diploid populations, this is often not true. Dominance and recessivity unexpectedly slow down the evolutionary process for weakly selected alleles. In particular, slightly advantageous dominant and mildly deleterious recessive mutations reach fixation slightly more slowly than neutral ones (at most 5%). This phenomenon determines genetic signatures opposite to those expected under strong selection, such as increased instead of decreased genetic diversity around the selected site. Furthermore, we characterize a new phenomenon: mildly deleterious recessive alleles, thought to represent a wide fraction of newly arising mutations, on average survive in a population slightly longer than neutral ones, before getting lost. Consequently, these mutations are on average slightly older than neutral ones, in contrast with previous expectations. Furthermore, they slightly increase the amount of weakly deleterious polymorphisms, as a consequence of the longer unconditional sojourn times compared to neutral mutations.KEYWORDS weak selection; diffusion approximation; dominance; recessive mutations A new allele emerging in a finite population usually has two possible fates-extinction or fixation. Selection affects the probability with which these occur and how long it will take. Thus, an advantageous allele has an increased chance to fix, due to positive selection, while a deleterious mutation has an increased chance of extinction. In both cases, the time until fixation and extinction is commonly thought to decrease with the strength of selection (Kimura and Ohta 1969b;van Herwaarden and Van Der Wal 2002). Kimura and Ohta (1969a,b) and Ewens (2004) applied diffusion theory to model finite populations, obtaining keystone approximations for the neutral case, in the absence of selection, or when selection is fairly strong. Recently it has been pointed out that in haploid models, in the presence of frequency-dependent fitness, the time to fixation of a positively selected allele can increase with the strength of selection (Altrock et al. 2010(Altrock et al. , 2012. In diploids, a newly arising mutation is usually expected to have a time to fixation longer than that of a neutral one in the case of overdominance, when the heterozygote has an higher fitness than the two homozygotes-a case usually referred to as heterozygote advantage or more generally balancing selection (Key et al. 2014). In the case of overdominance, both alleles would be maintained in an infinite population. In this article we unify these results, showing that in diploids, certain classes of mutations behave as slow sweeps/selective strolls: the time to fixation of a positively selected allele A can be slightly longer than in the...

Allele Age Under Non-Classical Assumptions is Clarified by an Exact Computational Markov Chain Approach

“…Recent work 10 – 12 has convincingly demonstrated, using primarily simulation and diffusion theory methods, that weakly selected alleles are sometimes expected to be older than neutral alleles observed at the same frequency when fitness in heterozygotes is non-additive. This idea was termed “selective strolls” by Mafessoni et al .…”

“…Later work added consideration of selection 9 , yielding the well-known result that allele age is expected to be symmetric with respect to the direction of selection, and that neutral alleles are expected to be older than selected alleles observed at the same frequency (the “Maruyama effect” hereafter). Recently, an interesting exception to these classical results has been pointed out 10 – 12 . Mafessoni et al .…”

“…Mafessoni et al . 12 showed that weakly selected rare alleles are expected to be about 5% older than neutral alleles observed at the same frequency, when heterozygote fitness is non-additive. This phenomenon appears to be an example of a more general behaviour recently termed ‘stochastic slowdown’ 10 , where weak selection counter-intuitively prolongs, rather than shortens, the average time to absorption.…”

“…It is important to understand the generality of these findings, since, as Mafessoni et al . 12 point out, many new mutations arising in a population are expected to be recessive and weakly deleterious, and it is conceivable that this slowdown effect could thereby mislead attempts to make inferences about natural selection.…”

Tree‐sequence recording in SLiM opens new horizons for forward‐time simulation of whole genomes

“…, and for exploring theoretical ideas about evolution (Assaf, Petrov, & Blundell, 2015;Champer et al, 2018;Haller, Mazzucco, & Dieckmann, 2013;Mafessoni & Lachmann, 2015), among other purposes. Because of this broad utility, there is a growing desire to run simulations with increased realism in a variety of areas: longer genomic regions up to the scale of full genome sequences, large populations, selection at multiple loci with linkage effects, complex demography, ecological interactions with other organisms and the environment, explicit space with continuous landscapes, spatial variation in environmental variables, spatial interactions such as competition and mate choice between organisms, and so forth.…”