scholarly journals Estimating the fitness effects of new mutations in the wild yeast Saccharomyces paradoxus

Author(s):  
V. Koufopanou ◽  
S. Lomas ◽  
I. J. Tsai ◽  
A. Burt
2020 ◽  
Author(s):  
Kimberly J. Gilbert ◽  
Stefan Zdraljevic ◽  
Daniel E. Cook ◽  
Asher D. Cutter ◽  
Erik C. Andersen ◽  
...  

ABSTRACTThe distribution of fitness effects for new mutations is one of the most theoretically important but difficult to estimate properties in population genetics. A crucial challenge to inferring the distribution of fitness effects (DFE) from natural genetic variation is the sensitivity of the site frequency spectrum to factors like population size change, population substructure, and non-random mating. Although inference methods aim to control for population size changes, the influence of non-random mating remains incompletely understood, despite being a common feature of many species. We report the distribution of fitness effects estimated from 326 genomes of Caenorhabditis elegans, a nematode roundworm with a high rate of self-fertilization. We evaluate the robustness of DFE inferences using simulated data that mimics the genomic structure and reproductive life history of C. elegans. Our observations demonstrate how the combined influence of self-fertilization, genome structure, and natural selection can conspire to compromise estimates of the DFE from extant polymorphisms. These factors together tend to bias inferences towards weakly deleterious mutations, making it challenging to have full confidence in the inferred DFE of new mutations as deduced from standing genetic variation in species like C. elegans. Improved methods for inferring the distribution of fitness effects are needed to appropriately handle strong linked selection and selfing. These results highlight the importance of understanding the combined effects of processes that can bias our interpretations of evolution in natural populations.


Genetics ◽  
2019 ◽  
Vol 211 (3) ◽  
pp. 1059-1073 ◽  
Author(s):  
Mark S. Hibbins ◽  
Matthew W. Hahn

Introgression is a pervasive biological process, and many statistical methods have been developed to infer its presence from genomic data. However, many of the consequences and genomic signatures of introgression remain unexplored from a methodological standpoint. Here, we develop a model for the timing and direction of introgression based on the multispecies network coalescent, and from it suggest new approaches for testing introgression hypotheses. We suggest two new statistics, D1 and D2, which can be used in conjunction with other information to test hypotheses relating to the timing and direction of introgression, respectively. D1 may find use in evaluating cases of homoploid hybrid speciation (HHS), while D2 provides a four-taxon test for polarizing introgression. Although analytical expectations for our statistics require a number of assumptions to be met, we show how simulations can be used to test hypotheses about introgression when these assumptions are violated. We apply the D1 statistic to genomic data from the wild yeast Saccharomyces paradoxus—a proposed example of HHS—demonstrating its use as a test of this model. These methods provide new and powerful ways to address questions relating to the timing and direction of introgression.


PLoS Genetics ◽  
2016 ◽  
Vol 12 (7) ◽  
pp. e1006155 ◽  
Author(s):  
David Peris ◽  
Quinn K. Langdon ◽  
Ryan V. Moriarty ◽  
Kayla Sylvester ◽  
Martin Bontrager ◽  
...  

2007 ◽  
Vol 8 (8) ◽  
pp. 610-618 ◽  
Author(s):  
Adam Eyre-Walker ◽  
Peter D. Keightley

2006 ◽  
Vol 361 (1475) ◽  
pp. 1941-1946 ◽  
Author(s):  
Vassiliki Koufopanou ◽  
Joseph Hughes ◽  
Graham Bell ◽  
Austin Burt

Little information is presently available on the factors promoting genetic divergence in eukaryotic microbes. We studied the spatial distribution of genetic variation in Saccharomyces paradoxus , the wild relative of Saccharomyces cerevisiae , from the scale of a few centimetres on individual oak trees to thousands of kilometres across different continents. Genealogical analysis of six loci shows that isolates from Europe form a single recombining population, and within this population genetic differentiation increases with physical distance. Between different continents, strains are more divergent and genealogically independent, indicating well-differentiated lineages that may be in the process of speciation. Such replicated populations will be useful for studies in population genomics.


2010 ◽  
Vol 7 (1) ◽  
pp. 98-100 ◽  
Author(s):  
Michael J. McDonald ◽  
Tim F. Cooper ◽  
Hubertus J. E. Beaumont ◽  
Paul B. Rainey

Theoretical studies of adaptation emphasize the importance of understanding the distribution of fitness effects (DFE) of new mutations. We report the isolation of 100 adaptive mutants—without the biasing influence of natural selection—from an ancestral genotype whose fitness in the niche occupied by the derived type is extremely low. The fitness of each derived genotype was determined relative to a single reference type and the fitness effects found to conform to a normal distribution. When fitness was measured in a different environment, the rank order changed, but not the shape of the distribution. We argue that, even with detailed knowledge of the genetic architecture underpinning the adaptive types (as is the case here), the DFEs remain unpredictable, and we discuss the possibility that general explanations for the shape of the DFE might not be possible in the absence of organism-specific biological details.


2021 ◽  
Author(s):  
Jun Chen ◽  
Thomas Bataillon ◽  
Sylvain Glémin ◽  
Martin Lascoux

2021 ◽  
Author(s):  
Deepa Agashe

During the 50 years since the genetic code was cracked, our understanding of the evolutionary consequences of synonymous mutations has undergone a dramatic shift. Synonymous codon changes were initially considered selectively neutral, and as such, exemplars of evolution via genetic drift. However, the pervasive and non-negligible fitness impacts of synonymous mutations are now clear across organisms. Despite the accumulated evidence, it remains challenging to incorporate the effects of synonymous changes in studies of selection, because the existing analytical framework was built with a focus on the fitness effects of nonsynonymous mutations. In this chapter, I trace the development of this topic and discuss the evidence that gradually transformed our thinking about the role of synonymous mutations in evolution. I suggest that our evolutionary framework should encompass the impacts of all mutations on various forms of information transmission. Folding synonymous mutations into a common distribution – rather than setting them apart as a distinct category – will allow a more complete and cohesive picture of the evolutionary consequences of new mutations.


2020 ◽  
Vol 10 (7) ◽  
pp. 2317-2326 ◽  
Author(s):  
Tom R. Booker

Characterizing the distribution of fitness effects (DFE) for new mutations is central in evolutionary genetics. Analysis of molecular data under the McDonald-Kreitman test has suggested that adaptive substitutions make a substantial contribution to between-species divergence. Methods have been proposed to estimate the parameters of the distribution of fitness effects for positively selected mutations from the unfolded site frequency spectrum (uSFS). Such methods perform well when beneficial mutations are mildly selected and frequent. However, when beneficial mutations are strongly selected and rare, they may make little contribution to standing variation and will thus be difficult to detect from the uSFS. In this study, I analyze uSFS data from simulated populations subject to advantageous mutations with effects on fitness ranging from mildly to strongly beneficial. As expected, frequent, mildly beneficial mutations contribute substantially to standing genetic variation and parameters are accurately recovered from the uSFS. However, when advantageous mutations are strongly selected and rare, there are very few segregating in populations at any one time. Fitting the uSFS in such cases leads to underestimates of the strength of positive selection and may lead researchers to false conclusions regarding the relative contribution adaptive mutations make to molecular evolution. Fortunately, the parameters for the distribution of fitness effects for harmful mutations are estimated with high accuracy and precision. The results from this study suggest that the parameters of positively selected mutations obtained by analysis of the uSFS should be treated with caution and that variability at linked sites should be used in conjunction with standing variability to estimate parameters of the distribution of fitness effects in the future.


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