Publications by authors named "Pierre Luisi"

17 Publications

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Ancient and modern mitogenomes from Central Argentina: new insights into population continuity, temporal depth and migration in South America.

Hum Mol Genet 2021 Apr 15. Epub 2021 Apr 15.

Universidad Nacional de Córdoba, Facultad de Filosofía y Humanidades, Departamento de Antropología, Córdoba, Argentina.

The inverted triangle shape of South America places Argentina territory as a geographical crossroads between the two principal peopling streams that followed either the Pacific or the Atlantic coasts, which could have then merged in Central Argentina. Although the genetic diversity from this region is therefore crucial to decipher past population movements in South America, its characterization has been overlooked so far. We report 92 modern and 22 ancient mitogenomes spanning a temporal range of 5000 years, which were compared to a large set of previously reported data. Leveraging this dataset representative of the mitochondrial diversity of the subcontinent, we investigate the maternal history of Central Argentina populations within a wider geographical context. We describe a large number of novel clades within the mitochondrial DNA tree, thus providing new phylogenetic interpretations for South America. We also identify several local clades of great temporal depth with continuity until present that stem directly from the founder haplotypes, suggesting that they originated in the region and expanded from there. Moreover, the presence of lineages characteristic of other South American regions reveals the existence of gene flow to Central Argentina. Finally, we report some lineages with discontinuous distribution across the Americas, which suggest the persistence of relic lineages likely linked to the first population arrivals. The present study represents to date the most exhaustive attempt to elaborate a Native American genetic map from modern and ancient complete mitochondrial genomes in Argentina and provides relevant information about the general process of settlement in South America.
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http://dx.doi.org/10.1093/hmg/ddab105DOI Listing
April 2021

Ancient genomes in South Patagonia reveal population movements associated with technological shifts and geography.

Nat Commun 2020 08 3;11(1):3868. Epub 2020 Aug 3.

Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.

Archaeological research documents major technological shifts among people who have lived in the southern tip of South America (South Patagonia) during the last thirteen millennia, including the development of marine-based economies and changes in tools and raw materials. It has been proposed that movements of people spreading culture and technology propelled some of these shifts, but these hypotheses have not been tested with ancient DNA. Here we report genome-wide data from 20 ancient individuals, and co-analyze it with previously reported data. We reveal that immigration does not explain the appearance of marine adaptations in South Patagonia. We describe partial genetic continuity since ~6600 BP and two later gene flows correlated with technological changes: one between 4700-2000 BP that affected primarily marine-based groups, and a later one impacting all <2000 BP groups. From ~2200-1200 BP, mixture among neighbors resulted in a cline correlated to geographic ordering along the coast.
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http://dx.doi.org/10.1038/s41467-020-17656-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400565PMC
August 2020

Fine-scale genomic analyses of admixed individuals reveal unrecognized genetic ancestry components in Argentina.

PLoS One 2020 16;15(7):e0233808. Epub 2020 Jul 16.

Departamento de Ecología, Genética y Evolución, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.

Similarly to other populations across the Americas, Argentinean populations trace back their genetic ancestry into African, European and Native American ancestors, reflecting a complex demographic history with multiple migration and admixture events in pre- and post-colonial times. However, little is known about the sub-continental origins of these three main ancestries. We present new high-throughput genotyping data for 87 admixed individuals across Argentina. This data was combined to previously published data for admixed individuals in the region and then compared to different reference panels specifically built to perform population structure analyses at a sub-continental level. Concerning the Native American ancestry, we could identify four Native American components segregating in modern Argentinean populations. Three of them are also found in modern South American populations and are specifically represented in Central Andes, Central Chile/Patagonia, and Subtropical and Tropical Forests geographic areas. The fourth component might be specific to the Central Western region of Argentina, and it is not well represented in any genomic data from the literature. As for the European and African ancestries, we confirmed previous results about origins from Southern Europe, Western and Central Western Africa, and we provide evidences for the presence of Northern European and Eastern African ancestries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233808PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365470PMC
September 2020

Population History and Gene Divergence in Native Mexicans Inferred from 76 Human Exomes.

Mol Biol Evol 2020 04;37(4):994-1006

National Laboratory of Genomics for Biodiversity (LANGEBIO), UGA, CINVESTAV, Irapuato, Guanajuato 36821, Mexico.

Native American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexico's Indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five Indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of Indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 KYA and subsequently diverging locally 6.5 and 5.7 KYA, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Rarámuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Rarámuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern Indigenous group from Oaxaca whose height is extremely low compared to other Native populations.
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http://dx.doi.org/10.1093/molbev/msz282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086176PMC
April 2020

First genome-wide association study of non-severe malaria in two birth cohorts in Benin.

Hum Genet 2019 Dec 30;138(11-12):1341-1357. Epub 2019 Oct 30.

Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Institut National de la Santé et de la Recherche Médicale, Villejuif, France.

Recent research efforts to identify genes involved in malaria susceptibility using genome-wide approaches have focused on severe malaria. Here, we present the first GWAS on non-severe malaria designed to identify genetic variants involved in innate immunity or innate resistance mechanisms. Our study was performed on two cohorts of infants from southern Benin (525 and 250 individuals used as discovery and replication cohorts, respectively) closely followed from birth to 18-24 months of age, with an assessment of a space- and time-dependent environmental risk of exposure. Both the recurrence of mild malaria attacks and the recurrence of malaria infections as a whole (symptomatic and asymptomatic) were considered. Post-GWAS functional analyses were performed using positional, eQTL, and chromatin interaction mapping to identify the genes underlying association signals. Our study highlights a role of PTPRT, a tyrosine phosphatase receptor involved in STAT3 pathway, in the protection against both mild malaria attacks and malaria infections (p = 9.70 × 10 and p = 1.78 × 10, respectively, in the discovery cohort). Strong statistical support was also found for a role of MYLK4 (meta-analysis, p = 5.29 × 10 with malaria attacks), and for several other genes, whose biological functions are relevant in malaria infection. Results shows that GWAS on non-severe malaria can successfully identify new candidate genes and inform physiological mechanisms underlying natural protection against malaria.
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http://dx.doi.org/10.1007/s00439-019-02079-5DOI Listing
December 2019

Genetic Load of Loss-of-Function Polymorphic Variants in Great Apes.

Genome Biol Evol 2016 Mar 26;8(3):871-7. Epub 2016 Mar 26.

Servei de Genòmica, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Catalonia, Spain

Loss of function (LoF) genetic variants are predicted to disrupt gene function, and are therefore expected to substantially reduce individual's viability. Knowing the genetic burden of LoF variants in endangered species is of interest for a better understanding of the effects of declining population sizes on species viability. In this study, we have estimated the number of LoF polymorphic variants in six great ape populations, based on whole-genome sequencing data in 79 individuals. Our results show that although the number of functional variants per individual is conditioned by the effective population size, the number of variants with a drastic phenotypic effect is very similar across species. We hypothesize that for those variants with high selection coefficients, differences in effective population size are not important enough to affect the efficiency of natural selection to remove them. We also describe that mostly CpG LoF mutations are shared across species, and an accumulation of LoF variants at olfactory receptor genes in agreement with its pseudogenization in humans and other primate species.
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http://dx.doi.org/10.1093/gbe/evw040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824148PMC
March 2016

Hierarchical boosting: a machine-learning framework to detect and classify hard selective sweeps in human populations.

Bioinformatics 2015 Dec 26;31(24):3946-52. Epub 2015 Aug 26.

Institut de Biologia Evolutiva (UPF-CSIC), Universitat Pompeu Fabra, Barcelona 08003, Spain.

Motivation: Detecting positive selection in genomic regions is a recurrent topic in natural population genetic studies. However, there is little consistency among the regions detected in several genome-wide scans using different tests and/or populations. Furthermore, few methods address the challenge of classifying selective events according to specific features such as age, intensity or state (completeness).

Results: We have developed a machine-learning classification framework that exploits the combined ability of some selection tests to uncover different polymorphism features expected under the hard sweep model, while controlling for population-specific demography. As a result, we achieve high sensitivity toward hard selective sweeps while adding insights about their completeness (whether a selected variant is fixed or not) and age of onset. Our method also determines the relevance of the individual methods implemented so far to detect positive selection under specific selective scenarios. We calibrated and applied the method to three reference human populations from The 1000 Genome Project to generate a genome-wide classification map of hard selective sweeps. This study improves detection of selective sweep by overcoming the classical selection versus no-selection classification strategy, and offers an explanation to the lack of consistency observed among selection tests when applied to real data. Very few signals were observed in the African population studied, while our method presents higher sensitivity in this population demography.

Availability And Implementation: The genome-wide results for three human populations from The 1000 Genomes Project and an R-package implementing the 'Hierarchical Boosting' framework are available at http://hsb.upf.edu/.
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http://dx.doi.org/10.1093/bioinformatics/btv493DOI Listing
December 2015

The genetics of East African populations: a Nilo-Saharan component in the African genetic landscape.

Sci Rep 2015 May 28;5:9996. Epub 2015 May 28.

Institut de Biologia Evolutiva (UPF-CSIC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.

East Africa is a strategic region to study human genetic diversity due to the presence of ethnically, linguistically, and geographically diverse populations. Here, we provide new insight into the genetic history of populations living in the Sudanese region of East Africa by analysing nine ethnic groups belonging to three African linguistic families: Niger-Kordofanian, Nilo-Saharan and Afro-Asiatic. A total of 500 individuals were genotyped for 200,000 single-nucleotide polymorphisms. Principal component analysis, clustering analysis using ADMIXTURE, FST statistics, and the three-population test were used to investigate the underlying genetic structure and ancestry of the different ethno-linguistic groups. Our analyses revealed a genetic component for Sudanese Nilo-Saharan speaking groups (Darfurians and part of Nuba populations) related to Nilotes of South Sudan, but not to other Sudanese populations or other sub-Saharan populations. Populations inhabiting the North of the region showed close genetic affinities with North Africa, with a component that could be remnant of North Africans before the migrations of Arabs from Arabia. In addition, we found very low genetic distances between populations in genes important for anti-malarial and anti-bacterial host defence, suggesting similar selective pressures on these genes and stressing the importance of considering functional pathways to understand the evolutionary history of populations.
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http://dx.doi.org/10.1038/srep09996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446898PMC
May 2015

Recent positive selection has acted on genes encoding proteins with more interactions within the whole human interactome.

Genome Biol Evol 2015 Apr 2;7(4):1141-54. Epub 2015 Apr 2.

Institute of Evolutionary Biology, Universitat Pompeu Fabra-CSIC, CEXS-UPF-PRBB, Barcelona, Catalonia, Spain Departament de Genètica i de Microbiologia, Grup de Biologia Evolutiva (GBE), Universitat Autonòma de Barcelona, Bellaterra, Spain

Genes vary in their likelihood to undergo adaptive evolution. The genomic factors that determine adaptability, however, remain poorly understood. Genes function in the context of molecular networks, with some occupying more important positions than others and thus being likely to be under stronger selective pressures. However, how positive selection distributes across the different parts of molecular networks is still not fully understood. Here, we inferred positive selection using comparative genomics and population genetics approaches through the comparison of 10 mammalian and 270 human genomes, respectively. In agreement with previous results, we found that genes with lower network centralities are more likely to evolve under positive selection (as inferred from divergence data). Surprisingly, polymorphism data yield results in the opposite direction than divergence data: Genes with higher centralities are more likely to have been targeted by recent positive selection during recent human evolution. Our results indicate that the relationship between centrality and the impact of adaptive evolution highly depends on the mode of positive selection and/or the evolutionary time-scale.
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http://dx.doi.org/10.1093/gbe/evv055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419801PMC
April 2015

Population and genomic lessons from genetic analysis of two Indian populations.

Hum Genet 2014 Oct 1;133(10):1273-87. Epub 2014 Jul 1.

Department of Genetics, University of Delhi South Campus, New Delhi, 110 021, India.

Indian demographic history includes special features such as founder effects, interpopulation segregation, complex social structure with a caste system and elevated frequency of consanguineous marriages. It also presents a higher frequency for some rare mendelian disorders and in the last two decades increased prevalence of some complex disorders. Despite the fact that India represents about one-sixth of the human population, deep genetic studies from this terrain have been scarce. In this study, we analyzed high-density genotyping and whole-exome sequencing data of a North and a South Indian population. Indian populations show higher differentiation levels than those reported between populations of other continents. In this work, we have analyzed its consequences, by specifically assessing the transferability of genetic markers from or to Indian populations. We show that there is limited genetic marker portability from available genetic resources such as HapMap or the 1,000 Genomes Project to Indian populations, which also present an excess of private rare variants. Conversely, tagSNPs show a high level of portability between the two Indian populations, in contrast to the common belief that North and South Indian populations are genetically very different. By estimating kinship from mates and consanguinity in our data from trios, we also describe different patterns of assortative mating and inbreeding in the two populations, in agreement with distinct mating preferences and social structures. In addition, this analysis has allowed us to describe genomic regions under recent adaptive selection, indicating differential adaptive histories for North and South Indian populations. Our findings highlight the importance of considering demography for design and analysis of genetic studies, as well as the need for extending human genetic variation catalogs to new populations and particularly to those with particular demographic histories.
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http://dx.doi.org/10.1007/s00439-014-1462-0DOI Listing
October 2014

Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences.

Genome Biol 2014 Jun 30;15(6):R88. Epub 2014 Jun 30.

Background: Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes.

Results: We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively.

Conclusions: We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.
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http://dx.doi.org/10.1186/gb-2014-15-6-r88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197830PMC
June 2014

Convergent evolution in European and Rroma populations reveals pressure exerted by plague on Toll-like receptors.

Proc Natl Acad Sci U S A 2014 Feb 3;111(7):2668-73. Epub 2014 Feb 3.

Institut de Biologia Evolutiva (Consejo Superior de Investigaciones Cientificas-Universitat Pompeu Fabra), Universitat Pompeu Fabra, 08003 Barcelona, Spain.

Recent historical periods in Europe have been characterized by severe epidemic events such as plague, smallpox, or influenza that shaped the immune system of modern populations. This study aims to identify signals of convergent evolution of the immune system, based on the peculiar demographic history in which two populations with different genetic ancestry, Europeans and Rroma (Gypsies), have lived in the same geographic area and have been exposed to similar environments, including infections, during the last millennium. We identified several genes under evolutionary pressure in European/Romanian and Rroma/Gipsy populations, but not in a Northwest Indian population, the geographic origin of the Rroma. Genes in the immune system were highly represented among those under strong evolutionary pressures in Europeans, and infections are likely to have played an important role. For example, Toll-like receptor 1 (TLR1)/TLR6/TLR10 gene cluster showed a strong signal of adaptive selection. Their gene products are functional receptors for Yersinia pestis, the agent of plague, as shown by overexpression studies showing induction of proinflammatory cytokines such as TNF, IL-1β, and IL-6 as one possible infection that may have exerted evolutionary pressures. Immunogenetic analysis showed that TLR1, TLR6, and TLR10 single-nucleotide polymorphisms modulate Y. pestis-induced cytokine responses. Other infections may also have played an important role. Thus, reconstruction of evolutionary history of European populations has identified several immune pathways, among them TLR1/TLR6/TLR10, as being shaped by convergent evolution in two human populations with different origins under the same infectious environment.
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http://dx.doi.org/10.1073/pnas.1317723111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932890PMC
February 2014

1000 Genomes Selection Browser 1.0: a genome browser dedicated to signatures of natural selection in modern humans.

Nucleic Acids Res 2014 Jan 25;42(Database issue):D903-9. Epub 2013 Nov 25.

Program for Population Genetics, Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), 08003 Barcelona, Spain, Population Genomics Node, National Institute for Bioinformatics (INB), Universitat Pompeu Fabra, 08003 Barcelona, Spain, Institute of Molecular Biology and Biotechnology-FORTH, Heraklion, Crete GR 700 13, Greece and Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.

Searching for Darwinian selection in natural populations has been the focus of a multitude of studies over the last decades. Here we present the 1000 Genomes Selection Browser 1.0 (http://hsb.upf.edu) as a resource for signatures of recent natural selection in modern humans. We have implemented and applied a large number of neutrality tests as well as summary statistics informative for the action of selection such as Tajima's D, CLR, Fay and Wu's H, Fu and Li's F* and D*, XPEHH, ΔiHH, iHS, F(ST), ΔDAF and XPCLR among others to low coverage sequencing data from the 1000 genomes project (Phase 1; release April 2012). We have implemented a publicly available genome-wide browser to communicate the results from three different populations of West African, Northern European and East Asian ancestry (YRI, CEU, CHB). Information is provided in UCSC-style format to facilitate the integration with the rich UCSC browser tracks and an access page is provided with instructions and for convenient visualization. We believe that this expandable resource will facilitate the interpretation of signals of selection on different temporal, geographical and genomic scales.
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http://dx.doi.org/10.1093/nar/gkt1188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965045PMC
January 2014

Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

PLoS One 2012 28;7(12):e53049. Epub 2012 Dec 28.

Inserm UMRS-946, Genetic Variability and Human Diseases, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.

VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2) is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK). This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8), and PRSS8) with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053049PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532425PMC
July 2013

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation.

BMC Evol Biol 2012 Jun 25;12:98. Epub 2012 Jun 25.

IBE, Institut de Biologia Evolutiva (UPF-CSIC), Parc de Recerca Biomèdica de Barcelona (PRBB), Dr, Aiguader, 88, 08003, Barcelona, Catalonia, Spain.

Background: Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints.

Results: Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1.

Conclusions: These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.
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http://dx.doi.org/10.1186/1471-2148-12-98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426484PMC
June 2012

Network-level and population genetics analysis of the insulin/TOR signal transduction pathway across human populations.

Mol Biol Evol 2012 May 1;29(5):1379-92. Epub 2011 Dec 1.

Institute of Evolutionary Biology CEXS-UPF-PRBB, Barcelona, Catalonia, Spain.

Genes and proteins rarely act in isolation, but they rather operate as components of complex networks of interacting molecules. Therefore, for understanding their evolution, it may be helpful to take into account the interaction networks in which they participate. It has been shown that selective constraints acting on genes depend on the position that they occupy in the network. Less understood is how the impact of local adaptation at the intraspecific level is affected by the network structure. Here, we analyzed the patterns of molecular evolution of 67 genes involved in the insulin/target of rapamycin (TOR) signal transduction pathway. This well-characterized pathway plays a key role in fundamental processes such as energetic metabolism, growth, reproduction, and aging and is involved in metabolic disorders such as obesity, insulin resistance, and diabetes. For that purpose, we combined genotype data from worldwide human populations with current knowledge of the structure and function of the pathway. We identified the footprint of recent positive selection in nine of the studied genomic regions. Most of the adaptation signals were observed among Middle East and North African, European, and Central South Asian populations. We found that positive selection preferentially targets the most central elements in the pathway, in contrast to previous observations in the whole human interactome. This observation indicates that the impact of positive selection on genes involved in the insulin/TOR pathway is affected by the pathway structure.
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http://dx.doi.org/10.1093/molbev/msr298DOI Listing
May 2012

The confounding effects of population structure, genetic diversity and the sampling scheme on the detection and quantification of population size changes.

Genetics 2010 Nov 25;186(3):983-95. Epub 2010 Aug 25.

Centre National de la Recherche Scientifique, Laboratoire Evolution et Diversité Biologique, Unité Mixte de Recherche, CNRS/Université Paul Sabatier 5174, F-31062 Toulouse, France.

The idea that molecular data should contain information on the recent evolutionary history of populations is rather old. However, much of the work carried out today owes to the work of the statisticians and theoreticians who demonstrated that it was possible to detect departures from equilibrium conditions (e.g., panmictic population/mutation-drift equilibrium) and interpret them in terms of deviations from neutrality or stationarity. During the last 20 years the detection of population size changes has usually been carried out under the assumption that samples were obtained from populations that can be approximated by a Wright-Fisher model (i.e., assuming panmixia, demographic stationarity, etc.). However, natural populations are usually part of spatial networks and are interconnected through gene flow. Here we simulated genetic data at mutation and migration-drift equilibrium under an n-island and a stepping-stone model. The simulated populations were thus stationary and not subject to any population size change. We varied the level of gene flow between populations and the scaled mutation rate. We also used several sampling schemes. We then analyzed the simulated samples using the Bayesian method implemented in MSVAR, the Markov Chain Monte Carlo simulation program, to detect and quantify putative population size changes using microsatellite data. Our results show that all three factors (genetic differentiation/gene flow, genetic diversity, and the sampling scheme) play a role in generating false bottleneck signals. We also suggest an ad hoc method to counter this effect. The confounding effect of population structure and of the sampling scheme has practical implications for many conservation studies. Indeed, if population structure is creating "spurious" bottleneck signals, the interpretation of bottleneck signals from genetic data might be less straightforward than it would seem, and several studies may have overestimated or incorrectly detected bottlenecks in endangered species.
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http://dx.doi.org/10.1534/genetics.110.118661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975287PMC
November 2010