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Thomas Bataillon

Publications and source records attributed to Thomas Bataillon.

3 recordsLinked to original sources

Inference of distribution of fitness effects and proportion of adaptive substitutions from polymorphism data

The distribution of fitness effects (DFE) encompasses deleterious, neutral and beneficial mutations. It conditions the evolutionary trajectory of populations, as well as the rate of adaptive molecular evolution (). Inference of DFE and from patterns of polymorphism (SFS) and divergence data has been a longstanding goal of evolutionary genetics. A widespread assumption shared by numerous methods developed so far to infer DFE and from such data is that beneficial mutations contribute only negligibly to the polymorphism data. Hence, a DFE comprising only deleterious mutations tends to be estimated from SFS data, and is only predicted by contrasting the SFS with divergence data from an outgroup. Here, we develop a hierarchical probabilistic framework that extends on previous methods and also can infer DFE and from polymorphism data alone. We use extensive simulations to examine the performance of our method. We show that both a full DFE, comprising both deleterious and beneficial mutations, and can be inferred without resorting to divergence data. We demonstrate that inference of DFE from polymorphism data alone can in fact provide more reliable estimates, as it does not rely on strong assumptions about a shared DFE between the outgroup and ingroup species used to obtain the SFS and divergence data. We also show that not accounting for the contribution of beneficial mutations to polymorphism data leads to substantially biased estimates of the DFE and . We illustrate these points using our newly developed framework, while also comparing to one of the most widely used inference methods available.

Evolutionary Biology

Inference under a Wright-Fisher model using an accurate beta approximation

The large amount and high quality of genomic data available today enables, in principle, accurate inference of evolutionary history of observed populations. The Wright-Fisher model is one of the most widely used models for this purpose. It describes the stochastic behavior in time of allele frequencies and the influence of evolutionary pressures, such as mutation and selection. Despite its simple mathematical formulation, exact results for the distribution of allele frequency (DAF) as a function of time are not available in closed analytic form. Existing approximations build on the computationally intensive diffusion limit, or rely on matching moments of the DAF. One of the moment-based approximations relies on the beta distribution, which can accurately describe the DAF when the allele frequency is not close to the boundaries (zero and one). Nonetheless, under a Wright-Fisher model, the probability of being on the boundary can be positive, corresponding to the allele being either lost or fixed. Here, we introduce the beta with spikes, an extension of the beta approximation, which explicitly models the loss and fixation probabilities as two spikes at the boundaries. We show that the addition of spikes greatly improves the quality of the approximation. We additionally illustrate, using both simulated and real data, how the beta with spikes can be used for inference of divergence times between populations, with comparable performance to existing state-of-the-art method.

Bioinformatics

GC-content evolution in bacterial genomes: the biased gene conversion hypothesis expands.

The characterization of functional elements in genomes relies on the identification of the footprints of natural selection. In this quest, taking into account neutral evolutionary processes such as mutation and genetic drift is crucial because these forces can generate patterns that may obscure or mimic signatures of selection. In mammals, and probably in many eukaryotes, another such confounding factor called GC-Biased Gene Conversion (gBGC) has been documented. This mechanism generates patterns identical to what is expected under selection for higher GC-content, specifically in highly recombining genomic regions. Recent results have suggested that a mysterious selective force favouring higher GC-content exists in Bacteria but the possibility that it could be gBGC has been excluded. Here, we show that gBGC is probably at work in most if not all bacterial species. First we find a consistent positive relationship between the GC-content of a gene and evidence of intra-genic recombination throughout a broad spectrum of bacterial clades. Second, we show that the evolutionary force responsible for this pattern is acting independently from selection on codon usage, and could potentially interfere with selection in favor of optimal AU-ending codons. A comparison with data from human populations shows that the intensity of gBGC in Bacteria is comparable to what has been reported in mammals. We propose that gBGC is not restricted to sexual Eukaryotes but also widespread among Bacteria and could therefore be an ancestral feature of cellular organisms. We argue that if gBGC occurs in bacteria, it can account for previously unexplained observations, such as the apparent non-equilibrium of base substitution patterns and the heterogeneity of gene composition within bacterial genomes. Because gBGC produces patterns similar to positive selection, it is essential to take this process into account when studying the evolutionary forces at work in bacterial genomes.

Evolutionary Biology