scholarly journals Soft selective sweeps in evolutionary rescue

2016 ◽  
Author(s):  
Benjamin A. Wilson ◽  
Pleuni S. Pennings ◽  
Dmitri A. Petrov
Keyword(s):  
Drug Resistance ◽  
Population Genetics ◽  
Population Genetic ◽  
Genetic Adaptation ◽  
Selective Sweeps ◽  
Adaptive Mutations ◽  
Evolutionary Rescue ◽  
Large Populations ◽  
Genetic Signatures ◽  
Soft Selective Sweeps

AbstractEvolutionary rescue occurs when a population that is declining in size because of an environmental change is rescued by genetic adaptation. Evolutionary rescue is an important phenomenon at the intersection of ecology and population genetics. While most population genetic models of evolutionary rescue focus on estimating the probability of rescue, we focus on whether one or more adaptive lineages contribute to evolutionary rescue. We find that when evolutionary rescue is likely, it is often driven by soft selective sweeps where multiple adaptive mutations spread through the population simultaneously. We give full analytic results for the probability of evolutionary rescue and the probability that evolutionary rescue occurs via soft selective sweeps in our model. We expect that these results will find utility in understanding the genetic signatures associated with various evolutionary rescue scenarios in large populations, such as the evolution of drug resistance in viral, bacterial, or eukaryotic pathogens.

scholarly journals More efficacious drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1

2015 ◽  
Author(s):  
Alison F Feder ◽  
Soo-Yon Rhee ◽  
Robert W Shafer ◽  
Dmitri A Petrov ◽  
Pleuni S Pennings
Keyword(s):  
Drug Resistance ◽  
Hiv Treatment ◽  
Adaptive Mutation ◽  
Selective Sweeps ◽  
Consensus Sequences ◽  
Adaptive Mutations ◽  
Slow Evolution ◽  
Soft Selective Sweeps ◽  
Hiv 1 ◽  
Evolution Proceeds

In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistant mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here we use 6,717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.

scholarly journals More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Alison F Feder ◽  
Soo-Yon Rhee ◽  
Susan P Holmes ◽  
Robert W Shafer ◽  
Dmitri A Petrov ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Treatment ◽  
Adaptive Mutation ◽  
Selective Sweeps ◽  
Resistance Mutations ◽  
Consensus Sequences ◽  
Adaptive Mutations ◽  
Slow Evolution ◽  
Effective Drugs ◽  
Hiv 1

In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.

scholarly journals Dominance shifts increase the likelihood of soft selective sweeps

2021 ◽  
Author(s):  
Pavitra Muralidhar ◽  
Carl Veller
Keyword(s):  
Selective Sweep ◽  
Primary Source ◽  
Pesticide Use ◽  
Selective Sweeps ◽  
Multiple Alleles ◽  
Standing Variation ◽  
Haplotypic Diversity ◽  
Evolutionary Rescue ◽  
Genetics Of Adaptation ◽  
Soft Selective Sweeps

AbstractGenetic models of adaptation to a new environment have typically assumed that the alleles involved maintain a constant fitness dominance across the old and new environments. However, theories of dominance suggest that this should often not be the case. Instead, the alleles involved should frequently shift from recessive deleterious in the old environment to dominant beneficial in the new environment. Here, we study the consequences of these expected dominance shifts for the genetics of adaptation to a new environment. We find that dominance shifts increase the likelihood that adaptation occurs from the standing variation, and that multiple alleles from the standing variation are involved (a soft selective sweep). Furthermore, we find that expected dominance shifts increase the haplotypic diversity of selective sweeps, rendering soft sweeps more detectable in small genomic samples. In cases where an environmental change threatens the viability of the population, we show that expected dominance shifts of newly beneficial alleles increase the likelihood of evolutionary rescue and the number of alleles involved. Finally, we apply our results to a well-studied case of adaptation to a new environment: the evolution of pesticide resistance at the Ace locus in Drosophila melanogaster. We show that, under reasonable demographic assumptions, the expected dominance shift of resistant alleles causes soft sweeps to be the most frequent outcome in this case, with the primary source of these soft sweeps being the standing variation at the onset of pesticide use, rather than recurrent mutation thereafter.

scholarly journals Genetic Adaptation in New York City Rats

2020 ◽  
Author(s):  
Arbel Harpak ◽  
Nandita Garud ◽  
Noah A Rosenberg ◽  
Dmitri A Petrov ◽  
Matthew Combs ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Urban Environments ◽  
Ancestral Population ◽  
Genetic Adaptation ◽  
Selective Sweeps ◽  
Locomotory Behavior ◽  
Extended Haplotypes ◽  
Genetic Signatures

Abstract Brown rats (Rattus norvegicus) thrive in urban environments by navigating the anthropocentric environment and taking advantage of human resources and by-products. From the human perspective, rats are a chronic problem that causes billions of dollars in damage to agriculture, health and infrastructure. Did genetic adaptation play a role in the spread of rats in cities? To approach this question, we collected whole-genome sequences from 29 brown rats from New York City (NYC) and scanned for genetic signatures of adaptation. We tested for (i) high-frequency, extended haplotypes that could indicate selective sweeps and (ii) loci of extreme genetic differentiation between the NYC sample and a sample from the presumed ancestral range of brown rats in northeast China. We found candidate selective sweeps near or inside genes associated with metabolism, diet, the nervous system and locomotory behavior. Patterns of differentiation between NYC and Chinese rats at putative sweep loci suggest that many sweeps began after the split from the ancestral population. Together, our results suggest several hypotheses on adaptation in rats living in close proximity to humans.

scholarly journals Soft Selective Sweeps in Evolutionary Rescue

Genetics ◽  
2017 ◽  
Vol 205 (4) ◽  
pp. 1573-1586 ◽  
Author(s):  
Benjamin A. Wilson ◽  
Pleuni S. Pennings ◽  
Dmitri A. Petrov
Keyword(s):  
Selective Sweeps ◽  
Evolutionary Rescue ◽  
Soft Selective Sweeps

scholarly journals The clarifying role of time series data in the population genetics of HIV

PLoS Genetics ◽  
2021 ◽  
Vol 17 (1) ◽  
pp. e1009050
Author(s):  
Alison F. Feder ◽  
Pleuni S. Pennings ◽  
Dmitri A. Petrov
Keyword(s):  
Time Series ◽  
Drug Resistance ◽  
Population Genetics ◽  
Time Series Data ◽  
Series Data ◽  
Selective Sweeps ◽  
Resistance Mutations ◽  
Resistance Evolution ◽  
Drug Resistance Mutations ◽  
Traditional Population

HIV can evolve remarkably quickly in response to antiretroviral therapies and the immune system. This evolution stymies treatment effectiveness and prevents the development of an HIV vaccine. Consequently, there has been a great interest in using population genetics to disentangle the forces that govern the HIV adaptive landscape (selection, drift, mutation, and recombination). Traditional population genetics approaches look at the current state of genetic variation and infer the processes that can generate it. However, because HIV evolves rapidly, we can also sample populations repeatedly over time and watch evolution in action. In this paper, we demonstrate how time series data can bound evolutionary parameters in a way that complements and informs traditional population genetic approaches. Specifically, we focus on our recent paper (Feder et al., 2016, eLife), in which we show that, as improved HIV drugs have led to fewer patients failing therapy due to resistance evolution, less genetic diversity has been maintained following the fixation of drug resistance mutations. Because soft sweeps of multiple drug resistance mutations spreading simultaneously have been previously documented in response to the less effective HIV therapies used early in the epidemic, we interpret the maintenance of post-sweep diversity in response to poor therapies as further evidence of soft sweeps and therefore a high population mutation rate (θ) in these intra-patient HIV populations. Because improved drugs resulted in rarer resistance evolution accompanied by lower post-sweep diversity, we suggest that both observations can be explained by decreased population mutation rates and a resultant transition to hard selective sweeps. A recent paper (Harris et al., 2018, PLOS Genetics) proposed an alternative interpretation: Diversity maintenance following drug resistance evolution in response to poor therapies may have been driven by recombination during slow, hard selective sweeps of single mutations. Then, if better drugs have led to faster hard selective sweeps of resistance, recombination will have less time to rescue diversity during the sweep, recapitulating the decrease in post-sweep diversity as drugs have improved. In this paper, we use time series data to show that drug resistance evolution during ineffective treatment is very fast, providing new evidence that soft sweeps drove early HIV treatment failure.

scholarly journals Genetic Adaptation in New York City Rats

2020 ◽  
Author(s):  
Arbel Harpak ◽  
Nandita Garud ◽  
Noah A. Rosenberg ◽  
Dmitri A. Petrov ◽  
Matthew Combs ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Urban Environments ◽  
Ancestral Population ◽  
Genetic Adaptation ◽  
Selective Sweeps ◽  
Locomotory Behavior ◽  
Extended Haplotypes ◽  
Genetic Signatures

AbstractBrown rats (Rattus norvegicus) thrive in urban environments by navigating the anthropocentric environment and taking advantage of human resources and by-products. From the human perspective, rats are a chronic problem that causes billions of dollars in damage to agriculture, health and infrastructure. Did genetic adaptation play a role in the spread of rats in cities? To approach this question, we collected whole-genome sequences from 29 brown rats from New York City (NYC) and scanned for genetic signatures of adaptation. We tested for (i) high-frequency, extended haplotypes that could indicate selective sweeps and (ii) loci of extreme genetic differentiation between the NYC sample and a sample from the presumed ancestral range of brown rats in northeast China. We found candidate selective sweeps near or inside genes associated with metabolism, diet, the nervous system and locomotory behavior. Patterns of differentiation between NYC and Chinese rats at putative sweep loci suggests that many sweeps began after the split from the ancestral population. Together, our results suggest several hypotheses on adaptation in rats living in close proximity to humans.

scholarly journals Soft selective sweeps in complex demographic scenarios

2014 ◽  
Author(s):  
Benjamin A Wilson ◽  
Dmitri Petrov ◽  
Philipp W Messer
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
De Novo ◽  
Analytical Framework ◽  
De Novo Mutation ◽  
Selective Sweeps ◽  
Effective Population ◽  
Weak Selection ◽  
Adaptive Mutations ◽  
Soft Selective Sweeps

Recent studies have shown that adaptation from de novo mutation often produces so-called soft selective sweeps, where adaptive mutations of independent mutational origin sweep through the population at the same time. Population genetic theory predicts that soft sweeps should be likely if the product of the population size and the mutation rate towards the adaptive allele is sufficiently large, such that multiple adaptive mutations can establish before one has reached fixation; however, it remains unclear how demographic processes affect the probability of observing soft sweeps. Here we extend the theory of soft selective sweeps to realistic demographic scenarios that allow for changes in population size over time. We first show that population bottlenecks can lead to the removal of all but one adaptive lineage from an initially soft selective sweep. The parameter regime under which such 'hardening' of soft selective sweeps is likely is determined by a simple heuristic condition. We further develop a generalized analytical framework, based on an extension of the coalescent process, for calculating the probability of soft sweeps under arbitrary demographic scenarios. Two important limits emerge within this analytical framework: In the limit where population size fluctuations are fast compared to the duration of the sweep, the likelihood of soft sweeps is determined by the harmonic mean of the variance effective population size estimated over the duration of the sweep; in the opposing slow fluctuation limit, the likelihood of soft sweeps is determined by the instantaneous variance effective population size at the onset of the sweep. We show that as a consequence of this finding the probability of observing soft sweeps becomes a function of the strength of selection. Specifically, in species with sharply fluctuating population size, strong selection is more likely to produce soft sweeps than weak selection. Our results highlight the importance of accurate demographic estimates over short evolutionary timescales for understanding the population genetics of adaptation from de novo mutation.

scholarly journals SFS_CODE: More Efficient and Flexible Forward Simulations

2015 ◽  
Author(s):  
Ryan D. Hernandez ◽  
Lawrence H. Uricchio
Keyword(s):  
Human Genome ◽  
Open Source Software ◽  
General Public ◽  
Population Genetic ◽  
Genome Structure ◽  
Supplementary Information ◽  
Selective Sweeps ◽  
Complex Models ◽  
Soft Selective Sweeps ◽  
General Public License

SUMMARY: Modern implementations of forward population genetic simulations are efficient and flexible, enabling the exploration of complex models that may otherwise be intractable. Here we describe an updated version of SFS_CODE, which has increased efficiency and includes many novel features. Among these features is an arbitrary model of dominance, the ability to simulate partial and soft selective sweeps, as well as track the trajectories of mutations and/or ancestries across multiple populations under complex models that are not possible under a coalescent framework. We also release sfs_coder, a Python wrapper to SFS_CODE allowing the user to easily generate command lines for common models of demography, selection, and human genome structure, as well as parse and simulate phenotypes from SFS_CODE output. Availability and Implementation: Our open source software is written in C and Python, and are available under the GNU General Public License at http://sfscode.sourceforge.net. Contact: [email protected] Supplementary information: Detailed usage information is available from the project website at http://sfscode.sourceforge.net.

scholarly journals On the unfounded enthusiasm for soft selective sweeps

2014 ◽  
Author(s):  
Jeffrey D. Jensen
Keyword(s):  
Experimental Evidence ◽  
Population Genetic ◽  
Natural Populations ◽  
Genetic Models ◽  
Relative Importance ◽  
Selective Sweeps ◽  
Beneficial Mutations ◽  
Adaptive Process ◽  
Soft Selective Sweeps

Underlying any understanding of the mode, tempo, and relative importance of the adaptive process in the evolution of natural populations is the notion of whether adaptation is mutation-limited. Two very different population genetic models have recently been proposed in which the rate of adaptation is not strongly limited by the rate at which newly arising beneficial mutations enter the population. This review discusses the theoretical underpinnings and requirements of these models, as well as the experimental insights on the parameters of relevance. Importantly, empirical and experimental evidence to date challenges the recent enthusiasm for invoking these models to explain observed patterns of variation in humans and Drosophila.

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