Population Genetics

People in the Computational and Molecular Population Genetics (CMPG) lab use molecular techniques, theoretical developments, and computer simulations to reconstruct the demographic history of populations and species from genetic data, and to test between alternative evolutionary scenarios.
We explore the genomic diversity of voles and humans in order to discover which genes have recently responded to selection, for instance to adapt to new environments.
We are also interested in quantifying the effect of range expansions and colonisation processes on genetic diversity, since these demographic events can lead to molecular signatures resembling those of selection.
We also develop and maintain computer programs to study and simulate the genetic diversity of populations, infer demographic parameters under complex scenarios, and detect loci under selection from genome scan.
The CMPG lab is affiliated to the Swiss Institute of Bioinformatics.

News

MER - Assessing the limits of local ancestry inference from small reference panels

Although many local ancestry inference (LAI) methods have been developed in the last decade, their performance was accessed using large reference panels, which are rarely available for non-model organisms or ancient samples.
In this paper, we compared the performance of two LAI methods (RFMix and MOSAIC) with the performance of a newly developed approach (simpLAI) that can be used even when reference populations consist of single individuals. Based on simulations of various demographic models, we also determined the limits of these LAI tools and proposed post-painting filtering steps to reduce false-positive rates and improve the precision and accuracy of the inferred admixed tracts. Besides providing a guide for using LAI, our work shows that reasonable inferences can be obtained from a single diploid genome per reference under demographic conditions that are not uncommon among past human groups and non-model organisms.

Congratulations to Qindong Tang for her PhD

On the 25th of October 2023, Qindong Tang successfully defended her PhD dissertation entitled “Unravelling cryptic radiation and high-altitude adaptation in a migratory bird species complex” supervised by Manuel Schweizer and Gerald Heckel. All the best Dr. Tang!

Congratulations to Xuejing Wang for her PhD

On the 6th of June 2023, Xuejing Wang successfully defended her Ph.D. dissertation entitled “On the balance of drift and selection: the evolution of the Orkney vole” supervised by Gerald Heckel. All the best, Dr. Wang!

Current Biology - Demographic history and genomic consequences of 10,000 generations of isolation in a wild mammal

In a new study in Current Biology, Xuejing Wang, Stephan Peischl and Gerald Heckel show that common voles (Microtus arvalis) on the Orkney archipelago have remained completely isolated for more than 5000 years. Orkney voles lost most genetic diversity and harbor high levels of putatively strongly deleterious mutations, yet results of computer simulations and the large current population sizes suggest rather mild effects on their fitness. While isolation leads to genetic deterioration, populations may still escape extinction and persist for very long periods of time.

SIB remarkable output

We are pleased to announce that our recent Cell paper (Marchi et al. 2022) has been selected by the Swiss Institute of Bioinformatics as one of its best achievement for the year 2022.

Cell - The genomic origins of the world’s first farmers

In a paper published in Cell, Nina Marchi and colleagues determine the precise genetic origins of the first Neolithic farming populations in Europe and Southwest Asia, as well as the processes and the timing of their differentiation. Demogenomic modeling of high-quality ancient genomes reveals that the early farmers of Anatolia and Europe emerged from a multiphase mixing of a Southwest Asian population with a strongly bottlenecked western hunter-gatherer population after the last glacial maximum. Moreover, the ancestors of the first farmers of Europe and Anatolia went through a period of extreme genetic drift during their westward range expansion, contributing highly to their genetic distinctiveness. This modeling elucidates the demographic processes at the root of the Neolithic transition and leads to a spatial interpretation of the population history of Southwest Asia and Europe during the late Pleistocene and early Holocene.

This paper has been selected as one of the SIB Remarkable Outputs 2022!

Genetics - Strong neutral sweeps occurring during a population contraction

In a paper published in Genetics, Antoine Moinet and colleagues study how dips of diversity emerge during a population bottleneck. A strong reduction in diversity around a specific locus is often interpreted as a recent rapid fixation of a positively selected allele, a phenomenon called a selective sweep. Rapid fixation of neutral variants can however lead to a similar reduction in local diversity, especially when the population experiences changes in population size, e.g. bottlenecks or range expansions. The fact that demographic processes can lead to signals of nucleotide diversity very similar to signals of selective sweeps is at the core of an ongoing discussion about the roles of demography and natural selection in shaping patterns of neutral variation. Here, we quantitatively investigate the shape of such neutral valleys of diversity under a simple model of a single population size change, and we compare it to signals of a selective sweep. We analytically describe the expected shape of such “neutral sweeps” and show that selective sweep valleys of diversity are, for the same fixation time, wider than neutral valleys. On the other hand, it is always possible to parameterize our model to find a neutral valley that has the same width as a given selected valley. Our findings provide further insight into how simple demographic models can create valleys of genetic diversity similar to those attributed to positive selection.

Nature - The eventful settlement history of South Pacific islands

Knowledge about the genetic diversity of human populations is essential to better understanding of overall settlement history and natural selection processes. However, the vast majority of genetic studies focus on populations of European origin, which represent only 16% of the world population. The genomic history of the South Pacific, on the other hand, has hardly been studied. In a new study published in Nature, an international research group led by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS) and the Collège de France has studied the settlement history of the inhabitants of the Pacific islands using genome sequencing. Our laboratory was involved in the demographic and historical inferences of the genomic data, which were analysed mainly with computer software developed in our group. The study, confirms archaeological findings that place human settlement of various islands in Oceania around 40,000 years ago. Furthermore, the scientists were able to prove that a period of genetic isolation between the islands followed this initial settlement.

Current Biology - Transition from background selection to associative overdominance (AOD) promotes diversity in regions of low recombination

Gilbert, Pouyet et al. combined mathematical modelling, individual-based simulations and human genomic data analysis to investigate how evolutionary forces determine patterns of genomic diversity. They find that selection against recessive deleterious mutations in regions of low recombination does not always lead to reduced diversity (compared to regions of intermediate recombination rate) as predicted by background selection (BGS) models. Contrastingly, selection against (partially) recessive mutations can lead to elevated levels of diversity at linked neutral sites and mimic patterns expected under balancing selection. Stable maintenance of distinct haplotypes in regions of low recombination does not necessarily come from any heterozygous advantage (i.e., overdominance for fitness) at any one of the genetic loci in this region. Rather, selection against recessive deleterious variants maintains complementary haplotypes if they all carry at least one harmful mutation at different positions This form of selection creates an increase of diversity at linked neutral sites, a process called associative overdominance (AOD). They derive the conditions for this AOD effect to occur and identify windows of the human genome where AOD seem to prevail. Negative selection in regions of low recombination may thus create more complex patterns of diversity than previously expected, emphasizing the necessity to modify the standard models for the effect of selection on linked neutral variation in low recombination regions to include harmful recessive mutations.

Nature - A complex settlement of Siberia reconstructed with ancient genomes

Our lab has modeled the settlement of North Eastern Siberia by modern humans, as part of a highly international and collaborative study led by Prof. Eske Willerslev director of The Lundbeck Foundation Centre for GeoGenetics in Copenhagen. The comparison of ancient and modern whole genomes has revealed that there had been at least three consecutive waves of migrations into that region since the last ice age, with little overlap between populations. Interestingly, the first wave was initiated more than 30 thousand ya by a now extinct population that had genetic affinities with western Eurasians, whereas the second population, which was related to East Asians colonized the region only after the last glacial maximum. Interestingly, members of this second wave are the individuals closest to Amerindians found outside the Americas to date, shedding new lights on the colonisation of this continent.

Nature Ecology and Evolution - Ancient admixture from an extinct ape lineage into bonobos.

In collaboration with Martin Kuhlwilm and Tomas Marques-Bonet from the Institut de Biologia Evolutiva in Barcelona, we looked for signatures of gene flow from unknown archaic populations, finding evidence for an ancient admixture event having occurred around 500 kya between bonobos and a divergent unknown lineage. This result reveals a complex population history in our closest living relatives, and suggest that admixture is a recurrent phenomenon in humans and other great ape populations.

PLOS Biology - Secondary contact between diverged host lineages entails ecological speciation in a European hantavirus.

A new study by former PhD student Moritz Saxenhofer working with Gerald Heckel shows that the formation of new Tula hantavirus “species” can be triggered by host hybridization. The analysis of a hybrid zone in the common vole Microtus arvalis demonstrated an extremely tight spatial association with distinct Tula virus clades. Phylogenetic analyses revealed that the divergence among virus clades was likely triggered by a shift of an ancestral virus between the previously diverged host lineages in the hybrid zone with subsequent adaptation. Virus genome sequences pointed to the amino-terminal part of the envelope protein as an important region for functional differentiation among these virus clades.

Congratulations to Dr. Nina Marchi for getting the “Prix de la Chancellerie des Universités de Paris” for her PhD thesis on the genetic diversity and the migratory behaviour of populations from Inner Asia.

This prize rewards the academic and scientific quality of PhD theses by students enrolled in universities in Paris region. This award also recognizes the engagement of her PhD supervisors, Prof. Evelyne Heyer and Dr. Laure Ségurel, and the excellence of the PhD host laboratory: Ecological Anthropology and Ethnobiology group (Musée de l’Homme, Paris, France).

During her PhD studies in anthropological genetics, Nina investigated how speciﬁc behaviours such as patrilocality, patrilineality or endogamy may affect the demographic history of human populations, by acting on the intensity of migration and genetic drift. To do so, she used combined genetic and ethnological data, collected in present-day Inner Asian populations that belong to two major cultural and linguistic groups and have different social organisations. Her doctoral research showed that cultural behaviours actively influence the neutral genetic diversity of the studied Inner Asian populations at different time and geographic scales. In a wider perspective, it illustrated how crucial considering cultural behaviours is in order to properly reconstruct the evolutionary history of our species.

PLoS Genetics - Mutation load dynamics during environmentally-driven range shifts

Kim Gilbert et al. have recently shown the consequences of range shifts on the accumulation of mutation load during spread across landscapes. As environments change, specialist species are expected to track the optimal environment they are adapted to, while generalist species are expected to spread widely. During this spread, individuals are subject to the additional challenge of accumulating deleterious alleles during repeated bottlenecks. We show that the process by which these alleles accumulate changes depending upon the speed at which populations spread over a landscape due to the combination of the efficacy of selection and the input of mutations into the population. These results suggest that the rate of environmental change across the globe will play a large role in the survival of specialist species.

eLife - Background selection and biased gene conversion affect more than 95% of the human genome and bias demographic inferences

A recent study from Pouyet et. al. shows that less than 5% of the human genome can be considered as "neutral" which is a striking finding given that actual coding genes only account for 1% of the human genome. Strong positive relationship is found between local recombination rate and genetic diversity: background selection is the primary process that skews genomic diversity, though GC-biased gene conversion also contributes. The paper determineds that only ~2.5% of SNPs act effectively neutrally and suggests that alternative definitions of neutrality lead to skewed allele frequency spectra which then have downstream affects when attempting to infer demographic history.

Congratulations to Lars Bosshard for his PhD

Congratulation to Dr. Lars Bosshard for his very successful PhD defense on 28.04.2018 of his thesis entitled "Investigation of the impact of bacterial range expansion and their functional genomic diversity" supervised by Stephan Peischl, Martin Ackermann and Laurent Excoffier.

Congratulations to Moritz Saxenhofer for his PhD

On the 4th of May 2018, Moritz Saxenhofer successfully defended his PhD dissertation entitled “Evolution and diversification of Tula hantavirus” supervised by Gerald Heckel.

Genetics - Population data from Quebec reveals the genetic consequences of rapid human expansions

The majority of the 6.5 million French Canadians living in Quebec today can trace their heritage to just 8500 settlers who formed clusters around the Saint Lawrence River in the early 17th century. Most remained near those riverside settlements until 200 years later, when some began colonizing more remote regions. Despite their shared heritage, the descendants of those who stayed near the river and those who moved on are already genetically divergent, and for unknown reasons, those living in more recently colonized areas of Quebec have a higher prevalence of recessive genetic disorders.

Science - Paleogenomics suggest inbreeding avoidance in early humans

Were our prehistoric ancestors aware of the dangers caused by procreation among close relatives? A study led by an international team of scientists, including SIB Swiss Institute of Bioinformatics Group Leader Laurent Excoffier and his team at the University of Bern, suggests that early humans might have purposely avoided mating with closely related partners. And this as early as 34,000 years ago.

Genetics - Accumulation of deleterious mutations during bacterial range expansions

Recent theoretical work suggested that deleterious mutations could accumulate during the range expansion of a species and negatively affect its fitness. We tested this prediction using an experimental evolution approach with bacteria growing on agar plates for 1650 generations. High mutation rate lines show a marked decrease in fitness measured in several environments, whereas low mutation rate lines show no such reduced fitness. Successfully expanding species thus accumulate deleterious mutations that impact their fitness, potentially limiting their ability to adapt to new environments. We posit that similar processes are likely to occur during the growth of solid tissues and tumors.

Proc. R. Soc. B - Geography uncovers ancient origins of RNA viruses

A new study conducted by Moritz Saxenhofer and Gerald Heckel shows that the time scales of virus evolutionary histories might be severely underestimated by state-of-the-art methods commonly used to date pathogen emergence. They included information about the geographic origin of virus samples to improve the age estimates for two European hantaviruses indicating that these are at least ten to a hundred times older than previously inferred based on sequence data alone. The results published with colleagues in the Proceedings of the Royal Society B provide valuable insights to better understand pathogen evolution and disease emergence.

Science - Chimpanzee genomic diversity reveals ancient admixture with bonobos

Modern non-African human genomes contain genomic remnants that suggest that there was interbreeding between ancient humans and archaic hominoid lineages. Now, an international consortium of researchers, including Prof. Laurent Excoffier and his team, show similar ancestral interbreeding between the ancestors of today's chimpanzees and bonobos. The study also provides population-specific genetic markers that may be valuable for conservation efforts.

Laurent Excoffier recognized by Thomson Reuters

Laurent Excoffier has just been listed in the Essential Science Indicators (ESI) developed by Thomson Reuters, in the field of computer science.
This list is based on journal article publication counts and citation data from Web of Science™ and serves as an indicator of the influence a researcher has in the scientific world.
Congratulations Laurent!

Nature - A genomic history of Aboriginal Australia

It remains debated how Australia was initially populated and how changes in language and culture in the continent happened. Australia contains some of the oldest archaeological evidence of modern humans outside Africa dating back to about 50,000 years. Still about 90% of Aboriginal Australians speak languages belonging to a single linguistic family that dates back no more than a few thousand years. The first population genomic study on Aboriginal Australians published today in Nature provide some of the answers. This study has been conducted by a group of international researchers, including nine Aboriginal leaders. It has been led by Prof. Eske Willerslev from the Copenhagen-based Centre for GeoGenetics, Cambridge University and the Sanger Institute. Assistant Prof. Anna-Sapfo Malaspinas, Prof. Laurent Excoffier and his team from the University of Bern and the SIB Swiss Institute of Bioinformatics are part of the study.

PNAS - Mutation load created during human expansions out of Africa

The further a population moves away from its place of origin, the more harmful mutations it will carry. This is the result of a study conducted by Prof. Laurent Excoffier and his team, as part of an international collaboration led by Brenna Henn from Stony Brook University and Carlos Bustamante from Stanford University.
The researchers analysed genomes of individuals across four continents while former studies had only been carried out on two populations. The study has now been published in the Proceedings of the National Academy of Sciences.

PLoS Genetics - Recent adaptation in threespine sticklebacks

New paper in PLoS Genetics on genomics of a very early stage of speciation by David Marques and colleagues. In only 150 years, threespine stickleback have evolved lake and stream ecotypes in Lake Constance, Central Europe. David found differentiation on multiple chromosomes persisting even in sympatry, suggesting early ecological speciation.

Congratulations to Miriam Zemanova for her PhD

On the 9th of December 2016, Miriam Zemanova successfully defended her PhD work, entitled Combining genetics, ecology and modelling to understand the invasion of Arion slugs, supervised by Eva Knop and Gerald Heckel.

Congratulations to Joana Meier for her PhD

On the 26th of May 2016, Joana Meier successfully defended her PhD work, entitled The role of hybridization in adaptive radiation: Genomic insights from Lake Victoria cichlids, supervised by Ole Seehausen, Laurent Excoffier and Catherine E. Wagner.

Congratulations to David Marques for his PhD

On the 10th of May 2016, David Marques successfully defended his PhD work, entitled Population Genomics of Adaptive Radiation: A Threespine Stickleback Perspective, supervised by Ole Seehausen, Laurent Excoffier and Catherine E. Wagner.

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