scholarly journals When is selection effective?

2014 ◽  
Author(s):  
Simon Gravel
Keyword(s):  
Genetic Load ◽  
Human Populations ◽  
Deleterious Alleles ◽  
Genome Wide ◽  
Biological Insight ◽  
Specific Allele ◽  
Mutational Damage ◽  
Modelling Assumptions ◽  
Random Fluctuations ◽  
Quantitative Explanation

AbstractDeleterious alleles can reach high frequency in small populations because of random fluctuations in allele frequency. This may lead, over time, to reduced average fitness. In that sense, selection is more ‘effective’ in larger populations. Recent studies have considered whether the different demographic histories across human populations have resulted in differences in the number, distribution, and severity of deleterious variants, leading to an animated debate. This article first seeks to clarify some terms of the debate by identifying differences in definitions and assumptions used in recent studies. We argue that variants of Morton, Crow and Muller’s ‘total mutational damage’ provide the soundest and most practical basis for such comparisons. Using simulations, analytical calculations, and 1000 Genomes data, we provide an intuitive and quantitative explanation for the observed similarity in genetic load across populations. We show that recent demography has likely modulated the effect of selection, and still affects it, but the net result of the accumulated differences is small. Direct observation of differential efficacy of selection for specific allele classes is nevertheless possible with contemporary datasets. By contrast, identifying average genome-wide differences in the efficacy of selection across populations will require many modelling assumptions, and is unlikely to provide much biological insight about human populations.

scholarly journals A continent-wide high genetic load in African buffalo revealed by clines in the frequency of deleterious alleles, genetic hitchhiking and linkage disequilibrium

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0259685
Author(s):  
Pim van Hooft ◽  
Wayne M. Getz ◽  
Barend J. Greyling ◽  
Bas Zwaan ◽  
Armanda D. S. Bastos
Keyword(s):  
Linkage Disequilibrium ◽  
Genetic Load ◽  
Male Body ◽  
African Buffalo ◽  
Latitude Range ◽  
Deleterious Alleles ◽  
Genome Wide ◽  
High Fraction ◽  
Frequency Occurrence ◽  
Microsatellite Alleles

A high genetic load can negatively affect population viability and increase susceptibility to diseases and other environmental stressors. Prior microsatellite studies of two African buffalo (Syncerus caffer) populations in South Africa indicated substantial genome-wide genetic load due to high-frequency occurrence of deleterious alleles. The occurrence of these alleles, which negatively affect male body condition and bovine tuberculosis resistance, throughout most of the buffalo’s range were evaluated in this study. Using available microsatellite data (2–17 microsatellite loci) for 1676 animals from 34 localities (from 25°S to 5°N), we uncovered continent-wide frequency clines of microsatellite alleles associated with the aforementioned male traits. Frequencies decreased over a south-to-north latitude range (average per-locus Pearson r = -0.22). The frequency clines coincided with a multilocus-heterozygosity cline (adjusted R2 = 0.84), showing up to a 16% decrease in southern Africa compared to East Africa. Furthermore, continent-wide linkage disequilibrium (LD) at five linked locus pairs was detected, characterized by a high fraction of positive interlocus associations (0.66, 95% CI: 0.53, 0.77) between male-deleterious-trait-associated alleles. Our findings suggest continent-wide and genome-wide selection of male-deleterious alleles driven by an earlier observed sex-chromosomal meiotic drive system, resulting in frequency clines, reduced heterozygosity due to hitchhiking effects and extensive LD due to male-deleterious alleles co-occurring in haplotypes. The selection pressures involved must be high to prevent destruction of allele-frequency clines and haplotypes by LD decay. Since most buffalo populations are stable, these results indicate that natural mammal populations, depending on their genetic background, can withstand a high genetic load.

scholarly journals The Strength of Selection Against Neanderthal Introgression

2015 ◽  
Author(s):  
Ivan Juric ◽  
Simon Aeschbacher ◽  
Graham Coop
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
Human Population ◽  
Genetic Load ◽  
Purifying Selection ◽  
Small Population ◽  
Secondary Contact ◽  
Human Populations ◽  
Effective Population ◽  
Deleterious Alleles

AbstractHybridization between humans and Neanderthals has resulted in a low level of Neanderthal ancestry scattered across the genomes of many modern-day humans. After hybridization, on average, selection appears to have removed Neanderthal alleles from the human population. Quantifying the strength and causes of this selection against Neanderthal ancestry is key to understanding our relationship to Neanderthals and, more broadly, how populations remain distinct after secondary contact. Here, we develop a novel method for estimating the genome-wide average strength of selection and the density of selected sites using estimates of Neanderthal allele frequency along the genomes of modern-day humans. We confirm that East Asians had somewhat higher initial levels of Neanderthal ancestry than Europeans even after accounting for selection. We find that the bulk of purifying selection against Neanderthal ancestry is best understood as acting on many weakly deleterious alleles. We propose that the majority of these alleles were effectively neutral—and segregating at high frequency—in Neanderthals, but became selected against after entering human populations of much larger effective size. While individually of small effect, these alleles potentially imposed a heavy genetic load on the early-generation human–Neanderthal hybrids. This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought.Author SummaryA small percentage of Neanderthal DNA is present in the genomes of many contemporary human populations due to hybridization tens of thousands of years ago. Much of this Neanderthal DNA appears to be deleterious in humans, and natural selection is acting to remove it. One hypothesis is that the underlying alleles were not deleterious in Neanderthals, but rather represent genetic incompatibilities that became deleterious only once they were introduced to the human population. If so, reproductive barriers must have evolved rapidly between Neanderthals and humans after their split. Here, we show that oberved patterns of Neanderthal ancestry in modern humans can be explained simply as a consequence of the difference in effective population size between Neanderthals and humans. Specifically, we find that on average, selection against individual Neanderthal alleles is very weak. This is consistent with the idea that Neanderthals over time accumulated many weakly deleterious alleles that in their small population were effectively neutral. However, after introgressing into larger human populations, those alleles became exposed to purifying selection. Thus, rather than being the result of hybrid incompatibilities, differences between human and Neanderthal effective population sizes appear to have played a key role in shaping our present-day shared ancestry.

scholarly journals Human Prehistoric Demography Revealed by the Polymorphic Pattern of CpG Transitions

2020 ◽  
Vol 37 (9) ◽  
pp. 2691-2698 ◽  
Author(s):  
Xiaoming Liu
Keyword(s):  
Population Dynamics ◽  
Population Expansion ◽  
Future Research ◽  
Human Populations ◽  
Neolithic Revolution ◽  
Cpg Sites ◽  
Hunting And Gathering ◽  
Genome Wide ◽  
Polymorphic Pattern ◽  
Improved Model

Abstract The prehistoric demography of human populations is an essential piece of information for illustrating our evolution. Despite its importance and the advancement of ancient DNA studies, our knowledge of human evolution is still limited, which is also the case for relatively recent population dynamics during and around the Holocene. Here, we inferred detailed demographic histories from 1 to 40 ka for 24 population samples using an improved model-flexible method with 36 million genome-wide noncoding CpG sites. Our results showed many population growth events that were likely due to the Neolithic Revolution (i.e., the shift from hunting and gathering to agriculture and settlement). Our results help to provide a clearer picture of human prehistoric demography, confirming the significant impact of agriculture on population expansion, and provide new hypotheses and directions for future research.

scholarly journals Genome-wide SNP data of Izumo and Makurazaki populations support inner-dual structure model for origin of Yamato people

2021 ◽  
Author(s):  
Timothy Jinam ◽  
Yosuke Kawai ◽  
Yoichiro Kamatani ◽  
Shunro Sonoda ◽  
Kanro Makisumi ◽  
...  
Keyword(s):  
Phylogenetic Network ◽  
Principal Component ◽  
Human Populations ◽  
Structure Model ◽  
Rice Farming ◽  
Asian Continent ◽  
Dual Structure ◽  
Snp Data ◽  
Genome Wide ◽  
Kagoshima Prefecture

AbstractThe “Dual Structure” model on the formation of the modern Japanese population assumes that the indigenous hunter-gathering population (symbolized as Jomon people) admixed with rice-farming population (symbolized as Yayoi people) who migrated from the Asian continent after the Yayoi period started. The Jomon component remained high both in Ainu and Okinawa people who mainly reside in northern and southern Japan, respectively, while the Yayoi component is higher in the mainland Japanese (Yamato people). The model has been well supported by genetic data, but the Yamato population was mostly represented by people from Tokyo area. We generated new genome-wide SNP data using Japonica Array for 45 individuals in Izumo City of Shimane Prefecture and for 72 individuals in Makurazaki City of Kagoshima Prefecture in Southern Kyushu, and compared these data with those of other human populations in East Asia, including BioBank Japan data. Using principal component analysis, phylogenetic network, and f4 tests, we found that Izumo, Makurazaki, and Tohoku populations are slightly differentiated from Kanto (including Tokyo), Tokai, and Kinki regions. These results suggest the substructure within Mainland Japanese maybe caused by multiple migration events from the Asian continent following the Jomon period, and we propose a modified version of “Dual Structure” model called the “Inner-Dual Structure” model.

scholarly journals Dynamics of natural selection in two generations (on the example of the population of the Kirovograd region)

2021 ◽  
Vol 29 ◽  
pp. 152-156
Author(s):  
K. K. Kovleva ◽  
N.A. Kozak
Keyword(s):  
Natural Selection ◽  
First Generation ◽  
Second Generation ◽  
Selection Index ◽  
Genetic Load ◽  
Modern Medicine ◽  
Reproductive Age ◽  
Human Populations ◽  
Medical Histories ◽  
Total Selection

Aim. In connection with the success of modern medicine, the pressure of natural selection in various civilized human populations is weakening, which leads to the accumulation of a genetic load. The purpose of this work was to trace the change in the intensity of natural selection among population of the Kirovograd region in two successive generations. Methods. The collection of material was carried out in 2020 and 2021. Anonymous questionnaires were conducted and medical histories of women of post-reproductive age of the Kirovograd region were studied. The first generation included 40 women born in 1937–1959; the second generation consists of 273 women born in 1960–1981. Results. The total selection index was 0.27 in the first generation, and 0.37 in the second generation. The percentage of women who have not had pregnancies increased from the first generation to the second from 2.5 to 3.7, respectively. Conclusions. The index of total selection in the Kirovograd region population for one generation increased by almost one and a half times (from 0.27 to 0.37), as well as the index of differential fertility (from 0.25 to 0.35). Keywords: reproductive characteristics, Kirovograd population, Crow's index, selection, generations.

scholarly journals Genotyping common, large structural variations in 5,202 genomes using pangenomes, the Giraffe mapper, and the vg toolkit

2020 ◽  
Author(s):  
Jouni Sirén ◽  
Jean Monlong ◽  
Xian Chang ◽  
Adam M. Novak ◽  
Jordan M. Eizenga ◽  
...  
Keyword(s):  
Human Populations ◽  
Structural Variations ◽  
Single Nucleotide ◽  
Human Genomes ◽  
Genome Wide ◽  
Sequence Graph ◽  
Long Read ◽  
Comparable Accuracy ◽  
Single Nucleotide Variations ◽  
Allelic Variations

ABSTRACTWe introduce Giraffe, a pangenome short read mapper that can efficiently map to a collection of haplotypes threaded through a sequence graph. Giraffe, part of the variation graph toolkit (vg)1, maps reads to thousands of human genomes at around the same speed BWA-MEM2 maps reads to a single reference genome, while maintaining comparable accuracy to VG-MAP, vg’s original mapper. We have developed efficient genotyping pipelines using Giraffe. We demonstrate improvements in genotyping for single nucleotide variations (SNVs), insertions and deletions (indels) and structural variations (SVs) genome-wide. We use Giraffe to genotype and phase 167 thousands structural variations ascertained from long read studies in 5,202 human genomes sequenced with short reads, including the complete 1000 Genomes Project dataset, at an average cost of $1.50 per sample. We determine the frequency of these variations in diverse human populations, characterize their complex allelic variations and identify thousands of expression quantitative trait loci (eQTLs) driven by these variations.

Genetic load and biological changes to extant humans

2020 ◽  
pp. 1-4
Author(s):  
Arthur Saniotis ◽  
Maciej Henneberg ◽  
Kazhaleh Mohammadi
Keyword(s):  
Natural Selection ◽  
Current Knowledge ◽  
Genetic Load ◽  
Differential Fertility ◽  
Medical Interventions ◽  
Deleterious Alleles ◽  
Gradual Process ◽  
Genetic Complexity ◽  
Sexual Recombination ◽  
Improved Sanitation

Abstract Extant humans are currently increasing their genetic load, which is informing present and future human microevolution. This has been a gradual process that has been rising over the last centuries as a consequence of improved sanitation, nutritional improvements, advancements in microbiology and medical interventions, which have relaxed natural selection. Moreover, a reduction in infant and child mortality and changing societal attitudes towards fertility have led to a decrease in total fertility rates (TFRs) since the 19th century. Generally speaking, decreases in differential fertility and mortality have meant that there is less opportunity for natural selection to eliminate deleterious mutations from the human gene pool. It has been argued that the average human may carry ~250–300 mutations that are mostly deleterious, as well as several hundred less-deleterious variants. These deleterious alleles in extant humans mean that our fitness is being constrained. While such alleles are viewed as reducing human fitness, they may also have had an adaptive function in the past, such as assisting in genetic complexity, sexual recombination and diploidy. Saying this, our current knowledge on these fitness compromising alleles is still lacking.

scholarly journals Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry

2019 ◽  
Vol 25 (10) ◽  
pp. 2455-2467 ◽  
Author(s):  
Tim B. Bigdeli ◽  
◽  
Giulio Genovese ◽  
Penelope Georgakopoulos ◽  
Jacquelyn L. Meyers ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Large Fraction ◽  
African Ancestry ◽  
Common Variant ◽  
Human Populations ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Common Genetic Variants

Abstract Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations.

scholarly journals Genetics of hypertension: discoveries from the bench to human populations

2014 ◽  
Vol 306 (1) ◽  
pp. F1-F11 ◽  
Author(s):  
Nora Franceschini ◽  
Thu H. Le
Keyword(s):  
Association Studies ◽  
Complex Trait ◽  
Experimental Models ◽  
Sodium Reabsorption ◽  
Human Populations ◽  
Genome Wide Association Studies ◽  
Blood Pressure Homeostasis ◽  
Genome Wide ◽  
Clinical Hypertension ◽  
Renal Sodium Reabsorption

Hypertension is a complex trait that is influenced by both heritable and environmental factors. The search for genes accounting for the susceptibility to hypertension has driven parallel efforts in human research and in research using experimental animals in controlled environmental settings. Evidence from rodent models of genetic hypertension and human Mendelian forms of hypertension and hypotension have yielded mechanistic insights into the pathways that are perturbed in blood pressure homeostasis, most of which converge at the level of renal sodium reabsorption. However, the bridging of evidence from these very diverse approaches to identify mechanisms underlying hypertension susceptibility and the translation of these findings to human populations and public health remain a challenge. Furthermore, findings from genome-wide association studies still require functional validation in experimental models. In this review, we highlight results and implications from key studies in experimental and clinical hypertension to date.

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