scholarly journals Identifying and classifying shared selective sweeps from multilocus data

2018 ◽  
Author(s):  
Alexandre M. Harris ◽  
Michael DeGiorgio
Keyword(s):  
Positive Selection ◽  
High Frequency ◽  
Selective Sweep ◽  
Ancestral Population ◽  
Human Populations ◽  
Platelet Response ◽  
Demographic Models ◽  
Asian Populations ◽  
Sub Saharan ◽  
Genomic Regions

AbstractPositive selection causes beneficial alleles to rise to high frequency, resulting in a selective sweep of the diversity surrounding the selected sites. Accordingly, the signature of a selective sweep in an ancestral population may still remain in its descendants. Identifying signatures of selection in the ancestor that are shared among its descendants is important to contextualize the timing of a sweep, but few methods exist for this purpose. We introduce the statistic SS-H12, which can identify genomic regions under shared positive selection across populations and is based on the theory of the expected haplotype homozygosity statistic H12, which detects recent hard and soft sweeps from the presence of high-frequency haplotypes. SS-H12, is distinct from other statistics that detect shared sweeps because it requires a minimum of only two populations, and properly identifies and differentiates between independent convergent sweeps and true ancestral sweeps, with high power and robustness to a variety of demographic models. Furthermore, we can apply SS-H12 in conjunction with the ratio of a different set of expected haplotype homozygosity statistics to further classify identified shared sweeps as hard or soft. Finally, we identified both previously-reported and novel shared sweep candidates from whole-genome sequences of global human populations. Previously-reported candidates include the well-characterized ancestral sweeps atLCTandSLC24A5in Indo-European populations, as well asGPHNworldwide. Novel candidates include an ancestral sweep atRGS18in sub-Saharan African populations involved in regulating the platelet response and implicated in sudden cardiac death, and a convergent sweep atC2CD5between European and East Asian populations that may explain their different insulin responses.Introduction

scholarly journals Identifying and Classifying Shared Selective Sweeps from Multilocus Data

Genetics ◽  
2020 ◽  
Vol 215 (1) ◽  
pp. 143-171 ◽  
Author(s):  
Alexandre M. Harris ◽  
Michael DeGiorgio
Keyword(s):  
Positive Selection ◽  
High Frequency ◽  
Selective Sweep ◽  
Ancestral Population ◽  
Platelet Response ◽  
Demographic Models ◽  
Asian Populations ◽  
Sub Saharan ◽  
Genomic Regions ◽  
Insulin Responses

Positive selection causes beneficial alleles to rise to high frequency, resulting in a selective sweep of the diversity surrounding the selected sites. Accordingly, the signature of a selective sweep in an ancestral population may still remain in its descendants. Identifying signatures of selection in the ancestor that are shared among its descendants is important to contextualize the timing of a sweep, but few methods exist for this purpose. We introduce the statistic SS-H12, which can identify genomic regions under shared positive selection across populations and is based on the theory of the expected haplotype homozygosity statistic H12, which detects recent hard and soft sweeps from the presence of high-frequency haplotypes. SS-H12 is distinct from comparable statistics because it requires a minimum of only two populations, and properly identifies and differentiates between independent convergent sweeps and true ancestral sweeps, with high power and robustness to a variety of demographic models. Furthermore, we can apply SS-H12 in conjunction with the ratio of statistics we term H2Tot and H1Tot to further classify identified shared sweeps as hard or soft. Finally, we identified both previously reported and novel shared sweep candidates from human whole-genome sequences. Previously reported candidates include the well-characterized ancestral sweeps at LCT and SLC24A5 in Indo-Europeans, as well as GPHN worldwide. Novel candidates include an ancestral sweep at RGS18 in sub-Saharan Africans involved in regulating the platelet response and implicated in sudden cardiac death, and a convergent sweep at C2CD5 between European and East Asian populations that may explain their different insulin responses.

scholarly journals Human genomic regions with exceptionally high or low levels of population differentiation identified from 911 whole-genome sequences

2014 ◽  
Author(s):  
Vincenza Colonna ◽  
Qasim Ayub ◽  
Yuan Chen ◽  
Luca Pagani ◽  
Pierre Luisi ◽  
...  
Keyword(s):  
Positive Selection ◽  
Population Differentiation ◽  
High Frequency ◽  
Balancing Selection ◽  
Human Populations ◽  
Background Population ◽  
Human Genomic ◽  
Low Levels ◽  
Candidate Regions ◽  
Genomic Regions

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 of 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 have identified known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.

scholarly journals Revisiting the Notion of Deleterious Sweeps

Genetics ◽  
2021 ◽  
Author(s):  
Parul Johri ◽  
Brian Charlesworth ◽  
Emma K Howell ◽  
Michael Lynch ◽  
Jeffrey D Jensen
Keyword(s):  
Positive Selection ◽  
Selective Sweep ◽  
Significant Proportion ◽  
Functional Genomic ◽  
Deleterious Mutations ◽  
Beneficial Mutations ◽  
Mating Population ◽  
Fixation Probabilities ◽  
Genomic Regions ◽  
Genomic Scans

Abstract It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites - both in the presence and absence of interference amongst deleterious mutations - and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.

A Microsatellite-Based Multilocus Screen for the Identification of Local Selective Sweeps

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 753-763 ◽  
Author(s):  
Christian Schlötterer
Keyword(s):  
Microsatellite Loci ◽  
Selective Sweep ◽  
Demographic History ◽  
Human Populations ◽  
Selective Sweeps ◽  
Test Statistic ◽  
Data Set ◽  
History Of ◽  
Microsatellite Mutation ◽  
Genomic Regions

AbstractWith the availability of completely sequenced genomes, multilocus scans of natural variability have become a feasible approach for the identification of genomic regions subjected to natural and artificial selection. Here, I introduce a new multilocus test statistic, ln RV, which is based on the ratio of observed variances in repeat number at a set of microsatellite loci in two groups of populations. The distribution of ln RV values captures demographic history of the populations as well as variation in microsatellite mutation among loci. Given that microsatellite loci associated with a recent selective sweep differ from the remainder of the genome, they are expected to fall outside of the distribution of neutral ln RV values. The ln RV test statistic is applied to a data set of 94 loci typed in eight non-African and two African human populations.

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 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 The Signature of Positive Selection at Randomly Chosen Loci

Genetics ◽  
2002 ◽  
Vol 160 (3) ◽  
pp. 1179-1189 ◽  
Author(s):  
Molly Przeworski
Keyword(s):  
Linkage Disequilibrium ◽  
Positive Selection ◽  
High Frequency ◽  
Selective Sweep ◽  
Random Mating ◽  
Significant Excess ◽  
Independent Evidence ◽  
Constant Size ◽  
Mating Population ◽  
Unequal Sampling

Abstract In Drosophila and humans, there are accumulating examples of loci with a significant excess of high-frequency-derived alleles or high levels of linkage disequilibrium, relative to a neutral model of a random-mating population of constant size. These are features expected after a recent selective sweep. Their prevalence suggests that positive directional selection may be widespread in both species. However, as I show here, these features do not persist long after the sweep ends: The high-frequency alleles drift to fixation and no longer contribute to polymorphism, while linkage disequilibrium is broken down by recombination. As a result, loci chosen without independent evidence of recent selection are not expected to exhibit either of these features, even if they have been affected by numerous sweeps in their genealogical history. How then can we explain the patterns in the data? One possibility is population structure, with unequal sampling from different subpopulations. Alternatively, positive selection may not operate as is commonly modeled. In particular, the rate of fixation of advantageous mutations may have increased in the recent past.

scholarly journals Revisiting the notion of deleterious sweeps

2020 ◽  
Author(s):  
Parul Johri ◽  
Brian Charlesworth ◽  
Emma K. Howell ◽  
Michael Lynch ◽  
Jeffrey D. Jensen
Keyword(s):  
Positive Selection ◽  
Selective Sweep ◽  
Significant Proportion ◽  
Functional Genomic ◽  
Deleterious Mutations ◽  
Beneficial Mutations ◽  
Mating Population ◽  
Fixation Probabilities ◽  
Genomic Regions ◽  
Genomic Scans

ABSTRACTIt has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations may generate selective sweep effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites, and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious sweeps are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.

Interactions between ecological and socio-economic drivers of Buruli ulcer burden in Sub-Saharan Africa: opportunities for an improved control

2018 ◽  
Author(s):  
Andes Garchitorena ◽  
Matthew H. Bonds ◽  
Jean-Francois Guégan ◽  
Benjamin Roche
Keyword(s):  
Socioeconomic Factors ◽  
Disease Transmission ◽  
Access To Health Care ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Sub Saharan Africa ◽  
Aquatic Environments ◽  
Human Populations ◽  
Complex Interactions ◽  
Sub Saharan

This chapter provides an overview of the complex interactions between ecological and socioeconomic factors for the development and control of Buruli ulcer in Sub-Saharan Africa. We review key ecological and evolutionary processes driving the environmental persistence and proliferation of Mycobacterium ulcerans, the causative agent, within aquatic environments, as well as transmission processes from these aquatic environments to human populations. We also outline key socioeconomic factors driving the economic and health burden of Buruli ulcer in endemic regions, revealed by reciprocal feedbacks between poverty, disease transmission from exposure aquatic environments and disease progression to severe stages owing to low access to health care. The implications of such insights for disease control, both in terms of limitations of current strategies and directions for the future, are discussed.

scholarly journals Selective sweep for an enhancer involucrin allele identifies skin barrier adaptation out of Africa

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mary Elizabeth Mathyer ◽  
Erin A. Brettmann ◽  
Alina D. Schmidt ◽  
Zane A. Goodwin ◽  
Inez Y. Oh ◽  
...  
Keyword(s):  
Selective Sweep ◽  
Skin Barrier ◽  
Human Migration ◽  
Epidermal Differentiation ◽  
Human Populations ◽  
Epidermal Differentiation Complex ◽  
Regulatory Module ◽  
Reporter Assays ◽  
Out Of Africa

AbstractThe genetic modules that contribute to human evolution are poorly understood. Here we investigate positive selection in the Epidermal Differentiation Complex locus for skin barrier adaptation in diverse HapMap human populations (CEU, JPT/CHB, and YRI). Using Composite of Multiple Signals and iSAFE, we identify selective sweeps for LCE1A-SMCP and involucrin (IVL) haplotypes associated with human migration out-of-Africa, reaching near fixation in European populations. CEU-IVL is associated with increased IVL expression and a known epidermis-specific enhancer. CRISPR/Cas9 deletion of the orthologous mouse enhancer in vivo reveals a functional requirement for the enhancer to regulate Ivl expression in cis. Reporter assays confirm increased regulatory and additive enhancer effects of CEU-specific polymorphisms identified at predicted IRF1 and NFIC binding sites in the IVL enhancer (rs4845327) and its promoter (rs1854779). Together, our results identify a selective sweep for a cis regulatory module for CEU-IVL, highlighting human skin barrier evolution for increased IVL expression out-of-Africa.

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