scholarly journals Genome-Wide Selection Scan in an Arabian Peninsula Population Identifies a TNKS Haplotype Linked to Metabolic Traits and Hypertension

2020 ◽  
Vol 12 (3) ◽  
pp. 77-87 ◽  
Author(s):  
Muthukrishnan Eaaswarkhanth ◽  
Andre Luiz Campelo dos Santos ◽  
Omer Gokcumen ◽  
Fahd Al-Mulla ◽  
Thangavel Alphonse Thanaraj
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Arabian Peninsula ◽  
Integrative Approach ◽  
Human Populations ◽  
Extended Haplotype ◽  
Major Health ◽  
Fitness Advantage ◽  
Genome Wide ◽  
Kuwaiti Population

Abstract Despite the extreme and varying environmental conditions prevalent in the Arabian Peninsula, it has experienced several waves of human migrations following the out-of-Africa diaspora. Eventually, the inhabitants of the peninsula region adapted to the hot and dry environment. The adaptation and natural selection that shaped the extant human populations of the Arabian Peninsula region have been scarcely studied. In an attempt to explore natural selection in the region, we analyzed 662,750 variants in 583 Kuwaiti individuals. We searched for regions in the genome that display signatures of positive selection in the Kuwaiti population using an integrative approach in a conservative manner. We highlight a haplotype overlapping TNKS that showed strong signals of positive selection based on the results of the multiple selection tests conducted (integrated Haplotype Score, Cross Population Extended Haplotype Homozygosity, Population Branch Statistics, and log-likelihood ratio scores). Notably, the TNKS haplotype under selection potentially conferred a fitness advantage to the Kuwaiti ancestors for surviving in the harsh environment while posing a major health risk to present-day Kuwaitis.

scholarly journals Genome-wide Selection Scan in an Arabian Peninsula Population Identifies a TNKS haplotype Linked to Metabolic Traits and Hypertension

2019 ◽  
Author(s):  
Muthukrishnan Eaaswarkhanth ◽  
Andre Luiz Campelo dos Santos ◽  
Omer Gokcumen ◽  
Fahd Al-Mulla ◽  
Thangavel Alphonse Thanaraj
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Arabian Peninsula ◽  
Integrative Approach ◽  
Human Populations ◽  
Extended Haplotype ◽  
Major Health ◽  
Fitness Advantage ◽  
Genome Wide ◽  
Kuwaiti Population

AbstractDespite the extreme and varying environmental conditions prevalent in the Arabian Peninsula, it has experienced several waves of human migrations following the out-of-Africa diaspora. Eventually, the inhabitants of the peninsula region adapted to the hot and dry environment. The adaptation and natural selection that shaped the extant human populations of the Arabian Peninsula region have been scarcely studied. In an attempt to explore natural selection in the region, we analyzed 662,750 variants in 583 Kuwaiti individuals. We searched for regions in the genome that display signatures of positive selection in the Kuwaiti population using an integrative approach in a conservative manner. We highlight a haplotype overlapping TNKS that showed strong signals of positive selection based on the results of the multiple selection tests conducted (integrated Haplotype Score, Cross Population Extended Haplotype Homozygosity, Population Branch Statistics, and log-likelihood ratio scores). Notably, the TNKS haplotype under selection potentially conferred a fitness advantage to the Kuwaiti ancestors for surviving in the harsh environment while posing a major health risk to present-day Kuwaitis.

scholarly journals Genome-wide detection and characterization of positive selection in human populations

Nature ◽  
2007 ◽  
Vol 449 (7164) ◽  
pp. 913-918 ◽  
Author(s):  
Pardis C. Sabeti ◽  
◽  
Patrick Varilly ◽  
Ben Fry ◽  
Jason Lohmueller ◽  
...  
Keyword(s):  
Positive Selection ◽  
Human Populations ◽  
Genome Wide

scholarly journals Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever

2012 ◽  
Vol 367 (1590) ◽  
pp. 868-877 ◽  
Author(s):  
Kristian G. Andersen ◽  
Ilya Shylakhter ◽  
Shervin Tabrizi ◽  
Sharon R. Grossman ◽  
Christian T. Happi ◽  
...  
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Lassa Fever ◽  
West African ◽  
Lassa Virus ◽  
Genome Wide ◽  
African Populations ◽  
Genome Wide Data ◽  
Differential Gene ◽  
Selection Of

Rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. With the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. Based on this approach, we have previously hypothesized that Lassa virus (LASV) may have been a driver of natural selection in West African populations where Lassa haemorrhagic fever is endemic. In this study, we provide further evidence for this notion. By applying tests for selection to genome-wide data from the International Haplotype Map Consortium and the 1000 Genomes Consortium, we demonstrate evidence for positive selection in LARGE and interleukin 21 ( IL21 ), two genes implicated in LASV infectivity and immunity. We further localized the signals of selection, using the recently developed composite of multiple signals method, to introns and putative regulatory regions of those genes. Our results suggest that natural selection may have targeted variants giving rise to alternative splicing or differential gene expression of LARGE and IL21 . Overall, our study supports the hypothesis that selective pressures imposed by LASV may have led to the emergence of particular alleles conferring resistance to Lassa fever, and opens up new avenues of research pursuit.

scholarly journals Identifying loci under positive selection in complex population histories

2018 ◽  
Author(s):  
Alba Refoyo-Martínez ◽  
Rute R. da Fonseca ◽  
Katrín Halldórsdóttir ◽  
Einar Árnason ◽  
Thomas Mailund ◽  
...  
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Human Population ◽  
Genomic Data ◽  
Human Populations ◽  
Selective Sweeps ◽  
Population Genomic ◽  
Complex Population ◽  
History Of ◽  
Over Time

AbstractDetailed modeling of a species’ history is of prime importance for understanding how natural selection operates over time. Most methods designed to detect positive selection along sequenced genomes, however, use simplified representations of past histories as null models of genetic drift. Here, we present the first method that can detect signatures of strong local adaptation across the genome using arbitrarily complex admixture graphs, which are typically used to describe the history of past divergence and admixture events among any number of populations. The method—called Graph-aware Retrieval of Selective Sweeps (GRoSS)—has good power to detect loci in the genome with strong evidence for past selective sweeps and can also identify which branch of the graph was most affected by the sweep. As evidence of its utility, we apply the method to bovine, codfish and human population genomic data containing multiple population panels related in complex ways. We find new candidate genes for important adaptive functions, including immunity and metabolism in under-studied human populations, as well as muscle mass, milk production and tameness in specific bovine breeds. We are also able to pinpoint the emergence of large regions of differentiation due to inversions in the history of Atlantic codfish.

scholarly journals Gene Flow and Natural Selection in Oceanic Human Populations Inferred from Genome-Wide SNP Typing

2008 ◽  
Vol 25 (8) ◽  
pp. 1750-1761 ◽  
Author(s):  
R. Kimura ◽  
J. Ohashi ◽  
Y. Matsumura ◽  
M. Nakazawa ◽  
T. Inaoka ◽  
...  
Keyword(s):  
Gene Flow ◽  
Natural Selection ◽  
Human Populations ◽  
Snp Typing ◽  
Genome Wide

scholarly journals Chromosome X-wide Analysis of Positive Selection in Human Populations: Common and Private Signals of Selection and its Impact on Inactivated Genes and Enhancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Pablo Villegas-Mirón ◽  
Sandra Acosta ◽  
Jessica Nye ◽  
Jaume Bertranpetit ◽  
Hafid Laayouni
Keyword(s):  
Positive Selection ◽  
X Chromosome ◽  
Genetic Basis ◽  
Target Genes ◽  
Regulatory Elements ◽  
Human Populations ◽  
Third Phase ◽  
Genome Wide ◽  
Private Signals ◽  
Sub Saharan

The ability of detecting adaptive (positive) selection in the genome has opened the possibility of understanding the genetic basis of population-specific adaptations genome-wide. Here, we present the analysis of recent selective sweeps, specifically in the X chromosome, in human populations from the third phase of the 1,000 Genomes Project using three different haplotype-based statistics. We describe instances of recent positive selection that fit the criteria of hard or soft sweeps, and detect a higher number of events among sub-Saharan Africans than non-Africans (Europe and East Asia). A global enrichment of neural-related processes is observed and numerous genes related to fertility appear among the top candidates, reflecting the importance of reproduction in human evolution. Commonalities with previously reported genes under positive selection are found, while particularly strong new signals are reported in specific populations or shared across different continental groups. We report an enrichment of signals in genes that escape X chromosome inactivation, which may contribute to the differentiation between sexes. We also provide evidence of a widespread presence of soft-sweep-like signatures across the chromosome and a global enrichment of highly scoring regions that overlap potential regulatory elements. Among these, enhancers-like signatures seem to present putative signals of positive selection which might be in concordance with selection in their target genes. Also, particularly strong signals appear in regulatory regions that show differential activities, which might point to population-specific regulatory adaptations.

scholarly journals Natural selection influenced the genetic architecture of brain structure, behavioral and neuropsychiatric traits

2020 ◽  
Author(s):  
Frank R Wendt ◽  
Gita A Pathak ◽  
Cassie Overstreet ◽  
Daniel S Tylee ◽  
Joel Gelernter ◽  
...  
Keyword(s):  
Natural Selection ◽  
Complex Traits ◽  
Association Studies ◽  
Model Fit ◽  
Human Populations ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Risk Alleles ◽  
Genome Wide ◽  
Improved Model

AbstractNatural selection has shaped the phenotypic characteristics of human populations. Genome-wide association studies (GWAS) have elucidated contributions of thousands of common variants with small effects on an individual’s predisposition to complex traits (polygenicity), as well as wide-spread sharing of risk alleles across traits in the human phenome (pleiotropy). It remains unclear how the pervasive effects of natural selection influence polygenicity in brain-related traits. We investigate these effects by annotating the genome with measures of background (BGS) and positive selection, indications of Neanderthal introgression, measures of functional significance including loss-of-function (LoF) intolerant and genic regions, and genotype networks in 75 brain-related traits. Evidence of natural selection was determined using binary annotations of top 2%, 1%, and 0.5% of selection scores genome-wide. We detected enrichment (q<0.05) of SNP-heritability at loci with elevated BGS (7 phenotypes) and in genic (34 phenotypes) and LoF-intolerant regions (67 phenotypes). BGS (top 2%) significantly predicted effect size variance for trait-associated loci (σ2 parameter) in 75 brain-related traits (β=4.39×10−5, p=1.43×10−5, model r2=0.548). By including the number of DSM-5 diagnostic combinations per psychiatric disorder, we substantially improved model fit (σ2 ~ BTop2% × Genic × diagnostic combinations; model r2=0.661). We show that GWAS with larger variance in risk locus effect sizes are collectively predicted by the effects of loci under strong BGS and in regulatory regions of the genome. We further show that diagnostic complexity exacerbates this relationship and perhaps dampens the ability to detect psychiatric risk loci.

scholarly journals Chromosome X-wide analysis of positive selection in human populations: from common and private signals to selection impact on inactivated genes and enhancers-like signatures

2021 ◽  
Author(s):  
Pablo Villegas Mirón ◽  
Sandra Acosta ◽  
Jessica Nye ◽  
Jaume Bertranpetit ◽  
Hafid Laayouni
Keyword(s):  
Positive Selection ◽  
X Chromosome ◽  
Target Genes ◽  
Regulatory Elements ◽  
Human Populations ◽  
Third Phase ◽  
Recent Positive Selection ◽  
Genome Wide ◽  
Private Signals ◽  
Sub Saharan

The ability of detecting adaptive (positive) selection in the genome has opened the possibility of understanding the genetic bases of population-specific adaptations genome-wide. Here we present the analysis of recent selective sweeps specifically in the X chromosome in different human populations from the third phase of the 1000 Genomes Project using three different haplotype-based statistics. We describe numerous instances of genes under recent positive selection that fit the regimes of hard and soft sweeps, showing a higher amount of detectable sweeps in sub-Saharan Africans than in non-Africans (Europe and East Asia). A global enrichment is seen in neural-related processes while numerous genes related to fertility appear among the top candidates, reflecting the importance of reproduction in human evolution. Commonalities with previously reported genes under positive selection are found, while particularly strong new signals are reported in specific populations or shared across different continental groups. We report an enrichment of signals in genes that escape X chromosome inactivation, which may contribute to the differentiation between sexes. We also provide evidence of a widespread presence of soft-sweep-like signatures across the chromosome and a global enrichment of highly scoring regions that overlap potential regulatory elements. Among these, enhancers-like signatures seem to present putative signals of positive selection that might be in concordance with selection in their target genes. Also, particularly strong signals appear in regulatory regions that show differential activities, which might point to population-specific regulatory adaptations.

scholarly journals Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy

2016 ◽  
Author(s):  
Sean G. Byars ◽  
Qin Qin Huang ◽  
Lesley-Ann Gray ◽  
Samuli Ripatti ◽  
Gad Abraham ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Genetic Variation ◽  
Natural Selection ◽  
Coronary Artery ◽  
Positive Selection ◽  
Genetic Risk ◽  
Human Reproduction ◽  
Human Populations ◽  
Modern Humans ◽  
Artery Disease

AbstractTraditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. This suggests the presence of widespread antagonistic-pleiotropic tradeoffs on CAD loci, which provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.Author SummaryHow genetic variation contributes to disease is complex, especially for those such as coronary artery disease (CAD) that develop over the lifetime of individuals. One of the fundamental questions about CAD — whose progression begins in young adults with arterial plaque accumulation leading to life-threatening outcomes later in life — is why natural selection has not removed or reduced this costly disease. It is the leading cause of death worldwide and has been present in human populations for thousands of years, implying considerable pressures that natural selection should have operated on. Our study provides new evidence that genes underlying CAD have recently been modified by natural selection and that these same genes uniquely and extensively contribute to human reproduction, which suggests that natural selection may have maintained genetic variation contributing to CAD because of its beneficial effects on fitness. This study provides novel evidence that CAD has been maintained in modern humans as a byproduct of the fitness advantages those genes provide early in human lifecycles.

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