Biology subjects

Jensen, J. D.

Publications and source records attributed to Jensen, J. D..

7 recordsLinked to original sources

bioRxiv2018

On the unfounded enthusiasm for soft selective sweeps II: examining recent evidence from humans, flies, and viruses

Since the initial description of the genomic patterns expected under models of positive selection acting on standing genetic variation and on multiple beneficial mutations--so-called soft selective sweeps--researchers have sought to identify these patterns in natural population data. Indeed, over the past two years, large-scale data analyses have argued that soft sweeps are pervasive across organisms of very different effective population size and mutation rate--humans, Drosophila, and HIV. Yet, others have evaluated the relevance of these models to natural populations, as well as the identifiability of the models relative to other known population-level processes, arguing that soft sweeps are likely to be rare. Here, we look to reconcile these opposing results by carefully evaluating three recent studies and their underlying methodologies. Using population genetic theory, as well as extensive simulation, we find that all three examples are prone to extremely high false-positive rates, incorrectly identifying soft sweeps under both hard sweep and neutral models. Furthermore, we demonstrate that well-fit demographic histories combined with rare hard sweeps serve as the more parsimonious explanation. These findings represent a necessary response to the growing tendency of invoking parameter-heavy, assumption-laden models of pervasive positive selection, and neglecting best practices regarding the construction of proper demographic null models.

evolutionary biology↗

bioRxiv2018

Inferring Demography and Selection in Organisms Characterized by Skewed Offspring Distributions

The recent increase in time-series population genomic data from experimental, natural, and ancient populations has been accompanied by a promising growth in methodologies for inferring demographic and selective parameters from such data. However, these methods have largely presumed that the populations of interest are well-described by the Kingman coalescent. In reality, many groups of organisms, including viruses, marine organisms, and some plants, protists, and fungi, typified by high variance in progeny number, may be best characterized by multiple-merger coalescent models. Estimation of population genetic parameters under Wright-Fisher assumptions for these organisms may thus be prone to serious mis-inference. We propose a novel method for the joint inference of demography and selection under the {Psi}-coalescent model, termed Multiple-Merger Coalescent Approximate Bayesian Computation, or MMC-ABC. We first quantify mis-inference under the Kingman and then demonstrate the superior performance of MMC-ABC under conditions of skewed offspring distribution. In order to highlight the utility of this approach, we re-analyzed previously published drug-selection lines of influenza A virus. We jointly inferred the extent of progeny-skew inherent to viral replication and identified putative drug-resistance mutations.

genetics↗

bioRxiv2018

The fitness consequences of genetic variation in wild populations of mice

Adaptive evolution can occur when genetic change affects traits subject to natural selection. Although selection is a deterministic process, adaptation can be difficult to predict in finite populations because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these connections using a combination of field and laboratory experiments. We conduct a large-scale manipulative field experiment with wild populations of deer mice in distinct habitats to directly estimate natural selection on pigmentation traits and next test whether this selection drives changes in allele frequency at an underlying pigment locus. We find that divergent cryptic phenotypes are repeatedly favoured in each habitat, leaving footprints of selection in the Agouti gene. Next, using transgenic experiments in Mus, we functionally test one of the Agouti mutations associated with survival, a Serine deletion in exon 2, and find that it causes lighter coat colour via changes in its protein binding properties. Finally, we show significant change in the frequency of this mutation in our field experiment. Together, our findings demonstrate how a sequence variant alters phenotype and show the ensuing ecological consequences that drive changes in population allele frequency, thereby revealing the full process of evolution by natural selection.

evolutionary biology↗

bioRxiv2018

The demographic history of African Drosophila melanogaster

As one of the most commonly utilized organisms in the study of local adaptation, an accurate characterization of the demographic history of Drosophila melanogaster remains as an important research question. This owes both to the inherent interest in characterizing the population history of this model organism, as well as to the well-established importance of an accurate null demographic model for increasing power and decreasing false positive rates in genomic scans for positive selection. While considerable attention has been afforded to this issue in non-African populations, less is known about the demographic history of African populations, including from the ancestral range of the species. While qualitative predictions and hypotheses have previously been forwarded, we here present a quantitative model fitting of the population history characterizing both the ancestral Zambian population range as well as the subsequently colonized west African populations, which themselves served as the source of multiple non-African colonization events. These parameter estimates thus represent an important null model for future investigations in to African and non-African D. melanogaster populations alike.

evolutionary biology↗

bioRxiv2018

The fitness landscape of the codon space across environments

Fitness landscapes map the relationship between genotypes and fitness. However, most fitness landscape studies ignore the genetic architecture imposed by the codon table and thereby neglect the potential role of synonymous mutations. To quantify the fitness effects of synonymous mutations and their potential impact on adaptation on a fitness landscape, we use a new software based on Bayesian Monte Carlo Markov Chain methods and reestimate selection coefficients of all possible codon mutations across 9 amino-acid positions in Saccharomyces cerevisiae Hsp90 across 6 environments. We quantify the distribution of fitness effects of synonymous mutations and show that it is dominated by many mutations of small or no effect and few mutations of larger effect. We then compare the shape of the codon fitness landscape across amino-acid positions and environments, and quantify how the consideration of synonymous fitness effects changes the evolutionary dynamics on these fitness landscapes. Together these results highlight a possible role of synonymous mutations in adaptation and indicate the potential mis-inference when they are neglected in fitness landscape studies.

evolutionary biology↗

bioRxiv2017

The evolutionary history of Nebraska deer mice: local adaptation in the face of strong gene flow

The interplay of gene flow, genetic drift, and local selective pressure is a dynamic process that has been well studied from a theoretical perspective over the last century. Wright and Haldane laid the foundation for expectations under an island-continent model, demonstrating that an island-specific beneficial allele may be maintained locally if the selection coefficient is larger than the rate of migration of the ancestral allele from the continent. Subsequent extensions of this model have provided considerably more insight. Yet, connecting theoretical results with empirical data has proven challenging, owing to a lack of information on the relationship between genotype, phenotype, and fitness. Here, we examine the demographic and selective history of deer mice in and around the Nebraska Sand Hills, a system in which variation at the Agouti locus affects cryptic coloration that in turn affects the survival of mice in their local habitat. We first genotyped 250 individuals from eleven sites along a transect spanning the Sand Hills at 660,000 SNPs across the genome. Using these genomic data, we found that deer mice first colonized the Sand Hills following the last glacial period. Subsequent high rates of gene flow have served to homogenize the majority of the genome between populations on and off the Sand Hills, with the exception of the Agouti pigmentation locus. Furthermore, mutations at this locus are strongly associated with the pigment traits that are strongly correlated with local soil coloration and thus responsible for cryptic coloration.

evolutionary biology↗

bioRxiv2017

Coalescent Processes With Skewed Offspring Distributions And Non-Equilibrium Demography

Non-equilibrium demography impacts coalescent genealogies leaving detectable, well-studied signatures of variation. However, similar genomic footprints are also expected under models of large reproductive skew, posing a serious problem when trying to make inference. Furthermore, current approaches consider only one of the two processes at a time, neglecting any genomic signal that could arise from their simultaneous effects, preventing the possibility of jointly inferring parameters relating to both offspring distribution and population history. Here, we develop an extended Moran model with exponential population growth, and demonstrate that the underlying ancestral process converges to a time-inhomogeneous psi-coalescent. However, by applying a non-linear change of time scale - analogous to the Kingman coalescent - we find that the ancestral process can be rescaled to its time-homogeneous analogue, allowing the process to be simulated quickly and efficiently. Furthermore, we derive analytical expressions for the expected site-frequency spectrum under the time-inhomogeneous psi-coalescent and develop an approximate-likelihood framework for the joint estimation of the coalescent and growth parameters. By means of extensive simulation, we demonstrate that both can be estimated accurately given linkage equilibrium, while linkage disequilibrium systematically biases growth rate estimates. In addition, not accounting for demography can lead to serious biases in the inferred coalescent model, with broad implications for genomic studies ranging from ecology to conservation biology. Finally, we use our method to analyze sequence data from Japanese sardine populations and find evidence of high variation in individual reproductive success, but few signs of a recent demographic expansion.

evolutionary biology↗