On the accumulation of deleterious mutations during range expansions

We investigate the effect of spatial range expansions on the evolution of fitness when beneficial and deleterious mutations co-segregate. We perform individual-based simulations of a uniform linear habitat and complement them with analytical approximations for the evolution of mean fitness at the edge of the expansion. We find that deleterious mutations accumulate steadily on the wave front during range expansions, thus creating an expansion load. Reduced fitness due to the expansion load is not restricted to the wave front but occurs over a large proportion of newly colonized habitats. The expansion load can persist and represent a major fraction of the total mutation load thousands of generations after the expansion. Our results extend qualitatively and quantitatively to two-dimensional expansions. The phenomenon of expansion load may explain growing evidence that populations that have recently expanded, including humans, show an excess of deleterious mutations. To test the predictions of our model, we analyze patterns of neutral and non-neutral genetic diversity in humans and find an excellent fit between theory and data

SIMCOAL 2.0: a program to simulate genomic diversity over large recombining regions in a subdivided population with a complex history

Summary: We present an extension of the program SIMCOAL, which allows for simulation of the genomic diversity of samples drawn from a set of populations with arbitrary patterns of migrations and complex demographic histories, including bottlenecks and various modes of demographic expansion. The main additions to the previous version include the possibility of arbitrary and heterogeneous recombination rates between adjacent loci and multiple coalescent events per generation, allowing for the simulation of very large samples and recombining genomic regions, together with the simulation of single nucleotide polymorphism data with frequency ascertainment bias. Availability: http://cmpg.unibe.ch/software/simcoal2/ Supplementary information: http://cmpg.unibe.ch/software/simcoal

Modern Humans Did Not Admix with Neanderthals during Their Range Expansion into Europe

The process by which the Neanderthals were replaced by modern humans between 42,000 and 30,000 before present is still intriguing. Although no Neanderthal mitochondrial DNA (mtDNA) lineage is found to date among several thousands of Europeans and in seven early modern Europeans, interbreeding rates as high as 25% could not be excluded between the two subspecies. In this study, we introduce a realistic model of the range expansion of early modern humans into Europe, and of their competition and potential admixture with local Neanderthals. Under this scenario, which explicitly models the dynamics of Neanderthals' replacement, we estimate that maximum interbreeding rates between the two populations should have been smaller than 0.1%. We indeed show that the absence of Neanderthal mtDNA sequences in Europe is compatible with at most 120 admixture events between the two populations despite a likely cohabitation time of more than 12,000 y. This extremely low number strongly suggests an almost complete sterility between Neanderthal females and modern human males, implying that the two populations were probably distinct biological species

fastsimcoal: a continuous-time coalescent simulator of genomic diversity under arbitrarily complex evolutionary scenarios

Motivation: Genetic studies focus on increasingly larger genomic regions of both extant and ancient DNA, and there is a need for simulation software to match these technological advances. We present here a new coalescent-based simulation program fastsimcoal, which is able to quickly simulate a variety of genetic markers scattered over very long genomic regions with arbitrary recombination patterns under complex evolutionary scenarios. Availability and Implementation: fastsimcoal is a C++ program compiled for Windows, MacOsX and Linux platforms. It is freely available at cmpg.unibe.ch/software/fastsimcoal/, together with its detailed user manual and example input files. Contact: [email protected] Supplementary Information: Supplementary data are available at Bioinformatics onlin

High variability and non-neutral evolution of the mammalian avpr1a gene

<p>Abstract</p> <p>Background</p> <p>The arginine-vasopressin 1a receptor has been identified as a key determinant for social behaviour in <it>Microtus </it>voles, humans and other mammals. Nevertheless, the genetic bases of complex phenotypic traits like differences in social and mating behaviour among species and individuals remain largely unknown. Contrary to previous studies focusing on differences in the promotor region of the gene, we investigate here the level of functional variation in the coding region (exon 1) of this locus.</p> <p>Results</p> <p>We detected high sequence diversity between higher mammalian taxa as well as between species of the genus <it>Microtus</it>. This includes length variation and radical amino acid changes, as well as the presence of distinct protein variants within individuals. Additionally, negative selection prevails on most parts of the first exon of the <it>arginine-vasopressin receptor 1a (avpr1a) </it>gene but it contains regions with higher rates of change that harbour positively selected sites. Synonymous and non-synonymous substitution rates in the <it>avpr1a </it>gene are not exceptional compared to other genes, but they exceed those found in related hormone receptors with similar functions.</p> <p>Discussion</p> <p>These results stress the importance of considering variation in the coding sequence of <it>avpr1a </it>in regards to associations with life history traits (e.g. social behaviour, mating system, habitat requirements) of voles, other mammals and humans in particular.</p

The impact of genetic surfing on neutral genomic diversity.

Range expansions have been common in the history of most species. Serial founder effects and subsequent population growth at expansion fronts typically lead to loss of genomic diversity along the expansion axis. A frequent consequence is the phenomenon of "gene surfing", where variants located near the expanding front can reach high frequencies or even fix in newly colonized territories. Although gene surfing events have been characterized thoroughly for a specific locus, their effects on linked genomic regions and on the overall patterns of genomic diversity have been little investigated. In this study, we simulated the evolution of whole genomes during several types of 1D and 2D range expansions differing by the extent of migration, founder events and recombination rates. We focused on the characterization of local dips of diversity, or "troughs", taken as a proxy for surfing events. We find that, for a given recombination rate, once we consider the amount of diversity lost since the beginning of the expansion, it is possible to predict the initial evolution of trough density and their average width irrespectively of the expansion condition. Furthermore, when recombination rates vary across the genome, we find that troughs are over-represented in regions of low recombination. Therefore, range expansions can leave local and global genomic signatures often interpreted as evidence of past selective events. Given the generality of our results, they could be used as a null model for species having gone through recent expansions, and thus be helpful to correctly interpret many evolutionary biology studies

Demogenomic inference from spatially and temporally heterogeneous samples

Modern and ancient genomes are not necessarily drawn from homogeneous populations, as they may have been collected from different places and at different times. This heterogeneous sampling can be an issue for demographic inferences and results in biased demographic parameters and incorrect model choice if not properly considered. When explicitly accounted for, it can result in very complex models and high data dimensionality that are difficult to analyse. In this paper, we formally study the impact of such spatial and temporal sampling heterogeneity on demographic inference, and we introduce a way to circumvent this problem. To deal with structured samples without increasing the dimensionality of the site frequency spectrum (SFS), we introduce a new structured approach to the existing program fastsimcoal2. We assess the efficiency and relevance of this methodological update with simulated and modern human genomic data. We particularly focus on spatial and temporal heterogeneities to evidence the interest of this new SFS-based approach, which can be especially useful when handling scattered and ancient DNA samples, as in conservation genetics or archaeogenetics