SIB Swiss Institute of Bioinformatics training courses (https://www.sib.swiss/training/upcoming-training-courses) are created by following a cycle of best practices in training, which have been defined by the trainers' communities in... more
SIB Swiss Institute of Bioinformatics training courses (https://www.sib.swiss/training/upcoming-training-courses) are created by following a cycle of best practices in training, which have been defined by the trainers' communities in ISCB, GOBLET, ELIXIR and the SIB Training group. Trainers from the SIB Training group are encouraged to attend <i>Train the trainer</i> courses. As a consequence, SIB courses are clearly defined with specific learning objectives, target audiences, prerequisites, and active learning activities. Course pages are described with Bioschemas specifications and metadata, which provide valuable information to enable trainees to assess whether the courses meet their needs and background knowledge, a step towards FAIR training. Quality and impact metrics, together with training needs, are continuously collected, providing indications as to whether courses and the annual program need to be adapted. The integration of these best practices, together ...
Release for the October 2021 edition of the course.
doi:10.1093/bioinformatics/btl280 Evolutionary simulations to detect functional lineage-specific genes
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Research Interests: Genomics, Gene Flow, Africa, Australia, Language, and 15 moreAboriginal History in Australia, Multidisciplinary, Nature, Evolutionary Genomics, Humans, Human Migration, Human Population Genetics, Modern Human Origins, Australian prehistory, Early human dispersal, New Guinea, Modern human dispersal, Human dispersals, Origins of Modern Humans, and Australian genetic diversity
Genetic surfing describes the spatial spread and increase in frequency of variants that are not lost by genetic drift and serial migrant sampling during a range expansion. Genetic surfing does not modify the total number of derived... more
Genetic surfing describes the spatial spread and increase in frequency of variants that are not lost by genetic drift and serial migrant sampling during a range expansion. Genetic surfing does not modify the total number of derived alleles in a population or in an individual genome, but it leads to a loss of heterozygosity along the expansion axis, implying that derived alleles are more often in homozygous state. Genetic surfing also affects selected variants on the wave front, making them behave almost like neutral variants during the expansion. In agreement with theoretical predictions, human genomic data reveals an increase in recessive mutation load with distance from Africa, an expansion load likely to have developed during the expansion of human populations out of Africa.
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The Out-of-Africa (OOA) dispersal ~50,000 years ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations... more
The Out-of-Africa (OOA) dispersal ~50,000 years ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from 7 geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were ...
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Research Interests: Bioinformatics, Evolutionary Biology, Genetics, Biological Anthropology, Molecular Biology, and 15 morePopulation Genetics, Molecular Evolution, Biology, Medicine, Mitochondrial DNA, Humans, Computer Simulation, Europe, Human Population Genetics, Female, Male, Molecular biology and evolution, Mediterranean region, Biochemistry and cell biology, and alleles
During the late Pleistocene, early anatomically modern humans coexisted in Europe with the anatomically archaic Neandertals for some thousand years. Under the recent variants of the multiregional model of human evolution, modern and... more
During the late Pleistocene, early anatomically modern humans coexisted in Europe with the anatomically archaic Neandertals for some thousand years. Under the recent variants of the multiregional model of human evolution, modern and archaic forms were different but related populations within a single evolving species, and both have contributed to the gene pool of current humans. Conversely, the Out-of-Africa model considers the transition between Neandertals and anatomically modern humans as the result of a demographic replacement, and hence it predicts a genetic discontinuity between them. Following the most stringent current standards for validation of ancient DNA sequences, we typed the mtDNA hypervariable region I of two anatomically modern Homo sapiens sapiens individuals of the Cro-Magnon type dated at about 23 and 25 thousand years ago. Here we show that the mtDNAs of these individuals fall well within the range of variation of today's humans, but differ sharply from the ...
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Research Interests: Bioinformatics, Computer Science, Computational Biology, Biology, Medicine, and 15 moreBiological Sciences, Phylogeny, Humans, Sequence alignment, Mathematical Sciences, Animals, High Power, Linkage Disequilibrium, Neutral Evolution, Hominidae, Large Scale, Base Sequence, Molecular Sequence Data, DNA mutational analysis, and Sequence similarity
Research Interests: Ancient History, Biological Anthropology, Biology, Ancient DNA Research, Medicine, and 15 moreItaly, Biological Sciences, Humans, Europe, Haplotypes, Fossils, Human Population Genetics, Ancient DNA, Ethnic Groups, Eastern Mediterranean, Genetic variation, Genetic Variability, Genetic distance, Bone and Bones, and Medical and Health Sciences
GSTA1 encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTA1 has several... more
GSTA1 encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTA1 has several functional SNPs within its promoter region that are responsible for a change in its expression by altering promoter function. This study aims to investigate distributions of GSTA1 promoter haplotypes across different human populations and to assess their impact on the expression of GSTA1. PHASE 2.1.1 was used to infer haplotypes and diplotypes of six GSTA1 promoter SNPs on 2501 individuals from 26 populations classified by the 1000 Genomes Project into five super-populations that included Africa (N = 660), America (N = 347), East Asia (N = 504), Europe (N = 502), and South Asia (N = 488). We used pairwise FST analysis to compare sub-populations and luciferase reporter assay (LRA) to evaluate the impact of each SNP on activation of transcription and interact...
Far northeastern Siberia has been occupied by humans for more than 40 thousand years. Yet, owing to a scarcity of early archaeological sites and human remains, its population history and relationship to ancient and modern populations... more
Far northeastern Siberia has been occupied by humans for more than 40 thousand years. Yet, owing to a scarcity of early archaeological sites and human remains, its population history and relationship to ancient and modern populations across Eurasia and the Americas are poorly understood. Here, we report 34 ancient genome sequences, including two from fragmented milk teeth found at the ~31.6 thousand-year-old (kya) Yana RHS site, the earliest and northernmost Pleistocene human remains found. These genomes reveal complex patterns of past population admixture and replacement events throughout northeastern Siberia, with evidence for at least three large-scale human migrations into the region. The first inhabitants, a previously unknown population of "Ancient North Siberians" (ANS), represented by Yana RHS, diverged ~38 kya from Western Eurasians, soon after the latter split from East Asians. Between 20 and 11 kya, the ANS population was largely replaced by peoples with ancestr...
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Recent theory predicts that the fitness of pioneer populations can decline when species expand their range, due to high rates of genetic drift on wave fronts making selection less efficient at purging deleterious variants. To test these... more
Recent theory predicts that the fitness of pioneer populations can decline when species expand their range, due to high rates of genetic drift on wave fronts making selection less efficient at purging deleterious variants. To test these predictions, we studied the fate of mutator bacteria expanding their range for 1650 generations on agar plates. In agreement with theory, we find that growth abilities of strains with a high mutation rate (HMR lines) decreased significantly over time, unlike strains with a lower mutation rate (LMR lines) that present 3-4 times fewer mutations. Estimation of the distribution of fitness effect (DFE) under a spatially explicit model reveals a mean negative effect for new mutations (-0.38%), but it suggests that both advantageous and deleterious mutations have accumulated during the experiment. Furthermore, we show that the fitness of HMR lines measured in different environments has decreased relative to the ancestor strain, whereas that of LMR lines rem...
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Humans have colonized the planet through a series of range expansions, which deeply impacted genetic diversity in newly settled areas and potentially increased the frequency of deleterious mutations on expanding wave fronts. To test this... more
Humans have colonized the planet through a series of range expansions, which deeply impacted genetic diversity in newly settled areas and potentially increased the frequency of deleterious mutations on expanding wave fronts. To test this prediction, we studied the genomic diversity of French Canadians who colonized Quebec in the 17th century. We used historical information and records from ∼4000 ascending genealogies to select individuals whose ancestors lived mostly on the colonizing wave front and individuals whose ancestors remained in the core of the settlement. Comparison of exomic diversity reveals that i) both new and low frequency variants are significantly more deleterious in front than in core individuals, ii) equally deleterious mutations are at higher frequencies in front individuals, and iii) front individuals are two times more likely to be homozygous for rare very deleterious mutations present in Europeans. These differences have emerged in the past 6-9 generations an...
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Discussions and detailed methods directly cited in the main paper; supplementary references; supplementary tables; supplementary figure legends. Format: PDF Size: 360KB
Given that retroposed copies of genes are presumed to lack the regulatory elements required for their expression, retroposition has long been considered a mechanism without functional relevance. However, through an in silico assay for... more
Given that retroposed copies of genes are presumed to lack the regulatory elements required for their expression, retroposition has long been considered a mechanism without functional relevance. However, through an in silico assay for transcriptional activity, we identify here >1,000 transcribed retrocopies in the human genome, of which at least ≈120 have evolved into bona fide genes. Among these, ≈50 retrogenes have evolved functions in testes, more than half of which were recruited as functional autosomal counterparts of X-linked genes during spermatogenesis. Generally, retrogenes emerge “out of the testis,” because they are often initially transcribed in testis and later evolve stronger and sometimes more diverse spatial expression patterns. We find a significant excess of transcribed retrocopies close to other genes or within introns, suggesting that retrocopies can exploit the regulatory elements and/or open chromatin of neighboring genes to become transcribed. In direct sup...
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Research Interests: Kinetics, Biology, Medicine, Biological Sciences, Phylogeny, and 15 moreHumans, Computer Simulation, Animals, Male, Polymerase Chain Reaction, Peptides, Genome, Gene Duplication, Biological evolution, Phenotype, Positive Selection, Likelihood Functions, Molecular Sequence Data, Medical and Health Sciences, and Expression pattern
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Research Interests: Genetics, Human Genetics, Biology, Molecular Genetics, Medicine, and 14 moreGenetic Diversity, Cytogenetics, Humans, Haplotypes, Clinical Genetics, Molecular Diversity, Physical chromosome mapping, European, Single Nucleotide Polymorphism, Linkage Disequilibrium, Mediterranean region, Genetic variation, Population Study, and Gene frequency
Molecular genetic data contain information on the history of populations. Evidence of prehistoric demographic expansions has been detected in the mitochondrial diversity of most human populations and in a Y-chromosome STR analysis, but... more
Molecular genetic data contain information on the history of populations. Evidence of prehistoric demographic expansions has been detected in the mitochondrial diversity of most human populations and in a Y-chromosome STR analysis, but not in a previous study of 11 Y-chromosome SNPs in Europeans. In this paper, we show that mismatch distributions and tests of mutation/drift equilibrium based on up to 166 Y-chromosome SNPs, in 46 samples from all continents, also fail to support an increase of the male effective population size. Computer simulations show that the low nuclear versus mitochondrial mutation rates cannot explain these results. However, ascertainment bias, i.e., when only highly variable SNP sites are typed, may be concealing any Y SNPs evidence for a recent, but not an ancient, increase in male effective population sizes. The results of our SNP analyses can be reconciled with the expansion of male effective population sizes inferred from STR loci, and with mitochondrial ...
Research Interests: Evolutionary Biology, Genetics, Biological Anthropology, Genetic Drift, Population Genetics, and 16 moreMolecular Evolution, Molecular Genetics, Molecular, Marriage, Humans, Computer Simulation, Mutation, Human Population Genetics, Male, Reproductive Success, Effective Population Size, Y chromosome, Single Nucleotide Polymorphism, Genetic variation, Mutation Rate, and Biochemistry and cell biology
Research Interests: Breeding, Multidisciplinary, Polyploidy, Software, Animals, and 3 moreFishes, Pedigree, and PLoS one
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Alternative splicing generates an enormous amount of functional and proteomic diversity in metazoan organisms. This process is probably central to the macromolecular and cellular complexity of higher eukaryotes. While most studies have... more
Alternative splicing generates an enormous amount of functional and proteomic diversity in metazoan organisms. This process is probably central to the macromolecular and cellular complexity of higher eukaryotes. While most studies have focused on the molecular mechanism triggering and controlling alternative splicing, as well as on its incidence in different species, its maintenance and evolution within populations has been little investigated. Here, we propose to address these questions by comparing the structural characteristics as well as the functional and transcriptional profiles of genes with monomorphic or polymorphic splicing, referred to as MS and PS genes, respectively. We find that MS and PS genes differ particularly in the number of tissues and cell types where they are expressed.We find a striking deficit of PS genes on the sex chromosomes, particularly on the Y chromosome where it is shown not to be due to the observed lower breadth of expression of genes on that chrom...