1,721,121 research outputs found
Response to Wyckelsma et al.: Loss of a-actinin-3 during human evolution provides superior cold resilience and muscle heat generation
No full textThe common loss-of-function mutation R577X in the structural muscle protein ACTN3 emerged as a potential target of positive selection from early studies and has been the focus of insightful physiological work suggesting a significant impact on muscle metabolism. Adaptation to cold climates has been proposed as a key adaptive mechanism explaining its global allele frequency patterns. Here, we re-examine this hypothesis analyzing modern (n = 3,626) and ancient (n = 1,651) genomic data by using allele-frequency as well as haplotype homozygosity-based methods. The presented results are more consistent with genetic drift rather than selection in cold climates as the main driver of the ACTN3 R577X frequency distribution in human populations across the world. This Matters Arising paper is in response to Wyckelsma et al. (2021),1 published in The American Journal of Human Genetics. See also the response by Wyckelsma et al. (2022),2 published in this issue.sponsorship: A.M. is grateful for institutional support by the Wellcome-MRC IMS-Bioinformatics and Biostatistics Core Facility. Part of the analyses were carried out with the facilities of the High-Performance Computing Center of the University of Tartu. This work was funded by the KU Leuven startup grant STG/18/021 (T.K.). (KU Leuven startup grant|STG/18/021)status: Publishe
Refining the use of linkage disequilibrium as a robust signature of selective sweeps
No full textDuring a selective sweep, characteristic patterns of linkage disequilibrium can arise in the genomic region surrounding a selected locus. These have been used to infer past selective sweeps. However, the recombination rate is known to vary substantially along the genome for many species. We here investigate the effectiveness of current (Kelly's ZnS and ωmax) and novel statistics at inferring hard selective sweeps based on linkage disequilibrium distortions under different conditions, including a human-realistic demographic model and recombination rate variation. When the recombination rate is constant, Kelly's ZnS offers high power, but is outperformed by a novel statistic that we test, which we call Zα. We also find this statistic to be effective at detecting sweeps from standing variation. When recombination rate fluctuations are included, there is a considerable reduction in power for all linkage disequilibrium-based statistics. However, this can largely be reversed by appropriately controlling for expected linkage disequilibrium using a genetic map. To further test these different methods, we perform selection scans on well-characterized HapMap data, finding that all three statistics—ωmax; Kelly’s ZnS; and Zα—are able to replicate signals at regions previously identified as selection candidates based on population differentiation or the site frequency spectrum. While ωmax replicates most candidates when recombination map data are not available, the ZnS and Zα statistics are more successful when recombination rate variation is controlled for. Given both this and their higher power in simulations of selective sweeps, these statistics are preferred when information on local recombination rate variation is available.</p
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Through the layers of the Ethiopian genome: a survey of human genetic variation based on genome-wide genotyping and re-sequencing data
Full text linkUnderstanding our evolutionary history as a species has since long been one of the most attracting and controversial themes of the scientific investigation. From its geographical position, outstanding fossil record and richness of human diversity, the Horn of Africa and, particularly, the Ethiopian region offers an unmatched opportunity to investigate our origins from a genetic perspective. To carry out a genome-wide survey of this region, 13 out of the estimated 80 extant Ethiopian populations were typed on an Illumina Omni 1M SNP array. The results showed a good concordance between genetic and linguistic stratification and, overall, a complex population structure placing the Ethiopians in between North and Sub Saharan Africans, due to the recent non African gene flow which was dated at around 3000 years ago. Furthermore the SNP array data unveiled putative traces of the out of Africa migrations as well as, in two of the typed populations, signatures of genetic adaptation to high altitude.
To obtain an unbiased, high resolution representation of the Ethiopian genetic landscape, 25 individuals from each of five populations were newly collected and sequenced on an Illumina HiSeq platform. These populations were chosen, from among the ones typed on the SNP array, to represent the main components of Ethiopian genetic diversity. Of the 25 samples per population, 24 were sequenced at low depth to generate a broad list of genetic variants, while one sample from each was sequenced at high depth to provide a higher resolution list of variants peculiar to each analysed population. The 125 Ethiopian genomes thus sequenced, while overall consistent with the genotyping results, described the Ethiopian populations in a less biased way than the SNP array data. Furthermore estimation of past effective population size fluctuations
from the individual genomes unveiled a unique pattern in the ancestry of the Ethiopian populations in the early stages of human evolution. These results provide a data resource which can be used in future analyses
Heterogeneity in genetic admixture across different regions of Argentina
Full text linkThe population of Argentina is the result of the intermixing between several groups, including Indigenous American, European and African populations. Despite the commonly held idea that the population of Argentina is of mostly European origin, multiple studies have shown that this process of admixture had an impact in the entire Argentine population. In the present study we characterized the distribution of Indigenous American, European and African ancestry among individuals from different regions of Argentina and evaluated the level of discrepancy between self-reported grandparental origin and genetic ancestry estimates. A set of 99 autosomal ancestry informative markers (AIMs) was genotyped in a sample of 441 Argentine individuals to estimate genetic ancestry. We used non-parametric tests to evaluate statistical significance. The average ancestry for the Argentine sample overall was 65% European (95%CI: 63-68%), 31% Indigenous American (28-33%) and 4% African (3-4%). We observed statistically significant differences in European ancestry across Argentine regions [Buenos Aires province (BA) 76%, 95%CI: 73-79%; Northeast (NEA) 54%, 95%CI: 49-58%; Northwest (NWA) 33%, 95%CI: 21-41%; South 54%, 95%CI: 49-59%; p<0.0001] as well as between the capital and immediate suburbs of Buenos Aires city compared to more distant suburbs [80% (95%CI: 75-86%) versus 68% (95%CI: 58-77%), p = 0.01]. European ancestry among individuals that declared all grandparents born in Europe was 91% (95%CI: 88-94%) compared to 54% (95%CI: 51-57%) among those with no European grandparents (p<0.001). Our results demonstrate the range of variation in genetic ancestry among Argentine individuals from different regions in the country, highlighting the importance of taking this variation into account in genetic association and admixture mapping studies in this population
Using genealogical trees to examine admixture between modern humans and Neandertals
Full text linkThis thesis uses genealogical trees to identify, date, and quantify patterns of admixture between Neandertals and individual modern human populations, using a combination of high quality data and parametric methodology. Previous methods on this subject have either approximated features of trees, or inferred them indirectly. Here, genealogical trees are used directly to understand the admixture process between humans and Neandertals by extending a recently developed method named CEPHi: Coalescent Estimation of Population History. CEPHi uses recombinationally cold regions of the human genome to build genealogical trees specifying the relationships between individuals in two input populations (one Neandertal, one human), including estimated population size histories, split times, and coalescence and mutation times.
Using CEPHi, a Neandertal-human population split time of ∼712,000 years in the past is estimated, as well as uncovering loci introduced by Neandertal-human admixture, revealing distinct bimodal distributions of estimated coalescence times between non-African and Neandertal haplotypes. A Neandertal population history is inferred, from the time of their split with humans up to ∼50,000 years ago (the fossil age), showing this archaic species to have suffered a bottleneck at this time, consistent with leaving Africa, followed by a further reduction to extinction.
Contrasting African-Neandertal and Eurasian-Neandertal analyses are used to define admixture using genealogical trees, and test our procedures in CEPHi via coalescent-based simulations. This region-level definition of admixture is used to specify sets of introgressed coldspots across 13 modern human populations. These sets are compared between pairs of populations, revealing information about the possible timing of interactions between Neandertals and modern humans, and sharing of admixture events between human groups, especially with respect to the split time between European and Asian populations. Online sets of introgressed regions for each of the four continents in our dataset are provided: African, American, Asian, and European.
Finally, in order to investigate the variation in time of contact between Neandertals and individual human populations, a novel method is described and implemented which dates admixture between individual human populations and Neandertals, using information from genealogical trees. Dates of admixture are estimated as ~50-60,000 years in the past in European populations, and ∼80-90,000 years in the past in Asian populations, suggestive of potentially somewhat distinct histories between European and Asian populations. This method can be applied to date any set of introgressed regions, including those shared between particular populations, enabling a clearer picture of the joint evolutionary history of modern humans, Neandertals, and other archaic species.</p
Exploring models in population biology through the simulation of species invasions, natural selection and market-mediated gene flow
No full textIn this thesis, I apply simulation techniques to investigate three questions in population biology, which focus on movement and natural selection. The first model assesses the theoretical implications of long-range dispersal in species invasions, identifying an important interaction between the representation of a finite population and the rate of population spread. The second investigates the genetic impact of movement distortions among domestic animals due to human economic activity, suggesting that the marketing of animals could fundamentally impact their genetic variation and distribution. My third model considers the problem of detecting evidence of positive natural selection in the genome, refining and testing statistics designed to identify which genes have offered a reproductive advantage in the past using population genetic data. These three simulation studies use very different approaches, and, separately, identify the critical and practical importance of assumptions frequently encountered in population models. Such assumptions - infinite population size, unbiased migration, and constant recombination rate - each lead to interesting properties of model behaviour, and may be relevant to interpretation and prediction in real world problems
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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