Éditeur(s) : HAL CCSD Society for Molecular Biology and Evolution
Résumé : International audience
Microsatellites (SSRs) are highly susceptible to expansions and contractions. When located in a coding sequence, the insertion or the deletion of a single unit for a mono-, di-, tetra-, or penta(nucleotide)-SSR creates a frameshift. As a consequence, one would expect to find only very few of these SSRs in coding sequences because of their strong deleterious potential. Unexpectedly, genomes contain many coding SSRs of all types. Here, we report on a study of their evolution in a phylogenetic context using the genomes of four primates: human, chimpanzee, orangutan, and macaque. In a set of 5,015 orthologous genes unambiguously aligned among the four species, we show that, except for tri- and hexa-SSRs, for which insertions and deletions are frequently observed, SSRs in coding regions evolve mainly by substitutions. We show that the rate of substitution in all types of coding SSRs is typically two times higher than in the rest of coding sequences. Additionally, we observe that although numerous coding SSRs are created and lost by substitutions in the lineages, their numbers remain constant. This last observation suggests that the coding SSRs have reached equilibrium. We hypothesize that this equilibrium involves a combination of mutation, drift, and selection. We thus estimated the fitness cost of mono-SSRs and show that it increases with the number of units. We finally show that the cost of coding mono-SSRs greatly varies from function to function, suggesting that the strength of the selection that acts against them can be correlated to gene functions.
ISSN: 1759-6653

hal-01544762
https://hal.archives-ouvertes.fr/hal-01544762
DOI : 10.1093/gbe/evt003

Éditeur(s) : HAL CCSD Wiley/Blackwell
Résumé : International audience
Microsatellites are widely used in population genetics to uncover recent evolutionary events. They are typically genotyped using capillary sequencer, which capacity is usually limited to 9, at most 12 loci for each run, and which analysis is a tedious task that is performed by hand. With the rise of next-generation sequencing (NGS), a much larger number of loci and individuals are available from sequencing: for example, on a single run of a GS Junior, 28 loci from 96 individuals are sequenced with a 30X cover. We have developed an algorithm to automatically and efficiently genotype microsatellites from a collection of reads sorted by individual (e.g. specific PCR amplifications of a locus or a collection of reads that encompass a locus of interest). As the sequencing and the PCR amplification introduce artefactual insertions or deletions, the set of reads from a single microsatellite allele shows several length variants. The algorithm infers, without alignment, the true unknown allele(s) of each individual from the observed distributions of microsatellites length of all individuals. MicNeSs, a python implementation of the algorithm, can be used to genotype any microsatellite locus from any organism and has been tested on 454 pyrosequencing data of several loci from fruit flies (a model species) and red deers (a nonmodel species). Without any parallelization, it automatically genotypes 22 loci from 441 individuals in 11 hours on a standard computer. The comparison of MicNeSs inferences to the standard method shows an excellent agreement, with some differences illustrating the pros and cons of both methods.
ISSN: 1755-098X

hal-01544754
https://hal.archives-ouvertes.fr/hal-01544754
DOI : 10.1111/1755-0998.12467

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The fitness landscapethe mapping between genotypes and fitnessdetermines properties of the process of adaptation. Several small genotypic fitness landscapes have recently been built by selecting a handful of beneficial mutations and measuring fitness of all combinations of these mutations. Here, we generate several testable predictions for the properties of these small genotypic landscapes under Fisher's geometric model of adaptation. When the ancestral strain is far from the fitness optimum, we analytically compute the fitness effect of selected mutations and their epistatic interactions. Epistasis may be negative or positive on average depending on the distance of the ancestral genotype to the optimum and whether mutations were independently selected, or coselected in an adaptive walk. Simulations show that genotypic landscapes built from Fisher's model are very close to an additive landscape when the ancestral strain is far from the optimum. However, when it is close to the optimum, a large diversity of landscape with substantial roughness and sign epistasis emerged. Strikingly, small genotypic landscapes built from several replicate adaptive walks on the same underlying landscape were highly variable, suggesting that several realizations of small genotypic landscapes are needed to gain information about the underlying architecture of the fitness landscape.
ISSN: 0014-3820

hal-01544760
https://hal.archives-ouvertes.fr/hal-01544760
DOI : 10.1111/evo.12545

Éditeur(s) : HAL CCSD SPRINGER
Résumé : International audience
A key question in evolutionary biology is the reproducibility of adaptation. This question can now be quantitatively analyzed using experimental evolution coupled to whole genome sequencing (WGS). With complete sequence data, one can assess convergence among replicate populations. In turn, convergence reflects the action of natural selection and also the breadth of the field of possible adaptive solutions. That is, it provides insight into how many genetic solutions or adaptive paths may lead to adaptation in a given environment. Convergence is both a property of an adaptive landscape and, reciprocally, a tool to study that landscape. In this chapter we present the links between convergence and the properties of adaptive landscapes with respect to two types of microbial experimental evolution. The first tries to reconstruct a full adaptive landscape using a handful of carefully identified mutations (the reductionist approach), while the second uses WGS of replicate experiments to infer properties of the adaptive landscape. Reductionist approaches have highlighted the importance of epistasis in shaping the adaptive landscape, but have also uncovered a wide diversity of landscape architectures. The WGS approach has uncovered a very high diversity of beneficial mutations that affect a limited set of genes or functions and also suggests some shortcomings of the reductionist approach. We conclude that convergence may be better defined at an integrated level, such as the genic level or even at a phenotypic level, and that integrated mechanistic models derived from systems biology may offer an interesting perspective for the analysis of convergence at all levels.
ECOLOGICAL GENOMICS: ECOLOGY AND THE EVOLUTION OF GENES AND GENOMES

ISBN : 978-94-007-7347-9; 978-94-007-7346-2
hal-01544757
https://hal.archives-ouvertes.fr/hal-01544757
DOI : 10.1007/978-94-007-7347-9__11

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research.
ISSN: 1061-4036

hal-01544763
https://hal.archives-ouvertes.fr/hal-01544763
DOI : 10.1038/ng.2601