Signals of Positive Selection in Human Populations of Siberia and European Russia

Russian Journal of Genetics - Human adaptation to extreme climatic and geographic conditions mediated by natural selection may be one of the major factors for formation of genetic structure in...     

Simultaneous Selection of Extreme Populations: A Subset Selection Approach

The problem of selecting a “best” (largest mean, or smallest mean) population from a collection of k independent populations was formulated and solved by Bechhofer (1954). Gupta (1965) solved another important problem, that of selecting a subset of populations containing the “best” population from the original collection of populations. Since then many variations of the problem have been considered. Tong (1969) and Lewis (1980) have investigated the problem of selecting extreme populations (populations with a largest, and populations with a smallest, mean) with respect to one and two standard populations, respectively. In this paper we study the selection of extreme populations in absence of any standard population. We formulate subset-selection procedures when variances are known and equal, and also in the most general case when they are unknown and unequal. Nonexistence of a single-stage procedure is noted for this latter case (even if variances are equal). A two-stage procedure and some of its associated properties are discussed. Tables needed for application are provided, as is a worked example.     

The Alto Salaverry child: a case of anemia from the Peruvian preceramic.

Excavations during 1974 at the Peruvian Preceramic site of Alto Salaverry led to the discovery of a child's skeleton. The fragmentary skeleton exhibits cribra orbitalia, a pitting of the orbital roof associated with anemia. This specimen provides the first evidence of anemia in a population of the predominantly non-agricultural Peruvian Preceramic and extends the antiquity of the pathology among Precolumbian Peruvians.     

Subset Selection for Exponential Populations: Determination of the Selection Constant

Given are k(≧2) exponential populations differing only in their location parameter. One wishes to choose the best one, that is the population with the largest value of the location parameter. A possible method for solving this problem is to select a subset of the k populations of size at least one which includes the best population with a required confidence P*(k^?1 ≤ P* ≤1). In this paper the required selection constant is determined for different values of k and P*. Also an approximation for the selection constant is derived. A comparison with the exact results is made.     

ABO blood groups in Peruvian mummies. I. An evaluation of techniques.

Blood groups of Peruvian mummies of known origin were determined by three different methods: agglutination-inhibition, induction of antibody production and mixed cell agglutination. The three techniques gave identical results, but the last two were useful in establishing the presence of H (O) antigen, while the first technique would not. The results indicate the presence of A, B, AB and O blood groups in America prior to known European contact. This suggests the need for a revision of concepts of blood groups in the American Indian.     

Genomic Targets of Positive Selection in Giant Mice from Gough Island

A key challenge in understanding how organisms adapt to their environments is to identify the mutations and genes that make it possible. By comparing patterns of sequence variation to neutral predictions across genomes, the targets of positive selection can be located. We applied this logic to house mice that invaded Gough Island (GI), an unusual population that shows phenotypic and ecological hallmarks of selection. We used massively parallel short-read sequencing to survey the genomes of 14 GI mice. We computed a set of summary statistics to capture diverse aspects of variation across these genome sequences, used approximate Bayesian computation to reconstruct a null demographic model, and then applied machine learning to estimate the posterior probability of positive selection in each region of the genome. Using a conservative threshold, 1,463 5-kb windows show strong evidence for positive selection in GI mice but not in a mainland reference population of German mice. Disproportionate shares of these selection windows contain genes that harbor derived nonsynonymous mutations with large frequency differences. Over-represented gene ontologies in selection windows emphasize neurological themes. Inspection of genomic regions harboring many selection windows with high posterior probabilities pointed to genes with known effects on exploratory behavior and body size as potential targets. Some genes in these regions contain candidate adaptive variants, including missense mutations and/or putative regulatory mutations. Our results provide a genomic portrait of adaptation to island conditions and position GI mice as a powerful system for understanding the genetic component of natural selection.     

The pubic scars of gestation and parturition in a group of pre-Columbian and colonial Peruvian mummies

The pubic scars of pregnancy and parturition as reported in the anthropological literature are a variant of the recognized clinical entity, osteitis pubis. The os pubis from 86 pre-Columbian and colonial Peruvian mummies were examined for this entity. Osteitis pubis was found in 13 pre-Columbian females (72.3%) and 19 colonial Indians (57.6%). Four of the colonial women were buried with newborn children and one had a four-month-old fetus in utero. This type of study has application in paleopathology and forensic medicine to show possible frequency of pregnancy in a population, but must be refined and quantitated to achieve any more than this. This study is of further interest as it demonstrates that racial groups have apparently a wide difference in frequency of this particular lesion of the pubic symphysis, a matter for further investigation.     

大珠母贝3个养殖种群的遗传多样性初步分析

大珠母贝（Pinctada maxima Jameson），俗称白蝶贝，是最大型的一种养殖海水珍珠的贝类，最大个体壳高达30cm以上，体重大于5k，是生产大型海水优质珍珠最理想的珠母贝。根据贝壳内表面外周珍珠质颜色的差异，可以分为金唇（Gold-lip，G）贝、银唇（Silver-lip，S）贝和黄唇（Yellow-lip，Y）贝等。     

Strategies for genetic conservation of trees in the Peruvian Amazon

Forestry practices and high rates of land clearance for agriculture are causing genetic erosion of valuable tree species in the Peruvian Amazon, thereby endangering the economic sustainability of rural communities and limiting Peru's opportunities for the development of new timber and non-timber forest products. The potential utility and limitations of six low-input interventions to help forestall further genetic erosion in the region are discussed, with a focus on local community involvement. Improved agroforestry systems may help reduce deforestation by increasing farm productivity, although methods to increase the currently low adoption rate of these technologies need to be developed. Use of strategic tree domestication techniques can also improve farm productivity and prevent inadvertent genetic drift and inbreeding associated with traditional domestication practices, although to have a major impact, current programs need to be extended across the region. Woodlot forestry could supplant selective extraction of timber and offers an attractive opportunity for poverty alleviation if appropriate credit and land tenure policies can be developed. However, it may also result in increased deforestation if activities on public land cannot be controlled. The implementation of improved seed collection systems and simple seed transfer guidelines would help to reduce the collection of seed of poor quality and low genetic diversity, and avoid maladapted plantings, although such programs are difficult to monitor and seed costs may increase. Strategic identification and design of in situ conservation areas would help to ensure the viability of conserved populations, but requires the forfeiture of significant revenue from timber concessions.     

Detecting and Characterizing Genomic Signatures of Positive Selection in Global Populations

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event.     

Nutritional influence on childhood development and genetic control of adolescent growth of Quechuas and Mestizos from the Peruvian Lowlands

The growth in height of 1,202 Quechua and Mestizo children aged 6 to 19 years of the province of Lamas in the Peruvian Eastern Lowlands was studied. As shown by evaluations of ABO, Rh systems, and skin reflectance measurements, the Quechuas are genetically different from the Mestizos. The heights of Quechuas and Mestizos were matched for nutritional status based on measurements of subcutaneous fat and body muscle. The study indicates that: (1) during childhood, Quechuas and Mestizos matched for the same nutritional status attain similar heights; (2) during adolescence (or after the age of 11 years), the Mestizos are significantly taller than the Quechuas of the same nutritional status; 3) during childhood, the relative difference in height between Quechuas and Mestizos matched for the same nutritional status is less than the difference between Quechuas (or Mestizos) of the same genetic composition characterized by good and poor nutritional status. These findings suggest that the influence of environmental factors, such as nutrition, have a greater influence in producing differences in body size during childhood than during adolescence. Conversely, the present findings support the hypothesis that the influence of genetic factors on body size are greater during adolescence than during childhood. However, comparison of adolescent samples of similar genetic composition (whether they be Quechuas or Mestizos), characterized by good and poor nutritional status, reveal large differences in height, suggesting that under conditions of malnutrition, the genetic control of growth is diminished.     

Tracing the Origin and Evolutionary Fate of Recent Gene Retrocopies in Natural Populations of the House Mouse

Although the contribution of retrogenes to the evolution of genes and genomes has long been recognized, the evolutionary patterns of very recently derived retrocopies that are still polymorphic within natural populations have not been much studied so far. We use here a set of 2,025 such retrocopies in nine house mouse populations from three subspecies (Mus musculus domesticus, M. m. musculus, and M. m. castaneus) to trace their origin and evolutionary fate. We find that ancient house-keeping genes are significantly more likely to generate retrocopies than younger genes and that the propensity to generate a retrocopy depends on its level of expression in the germline. Although most retrocopies are detrimental and quickly purged, we focus here on the subset that appears to be neutral or even adaptive. We show that retrocopies from X-chromosomal parental genes have a higher likelihood to reach elevated frequencies in the populations, confirming the notion of adaptive effects for “out-of-X” retrogenes. Also, retrocopies in intergenic regions are more likely to reach higher population frequencies than those in introns of genes, implying a more detrimental effect when they land within transcribed regions. For a small subset of retrocopies, we find signatures of positive selection, indicating they were involved in a recent adaptation process. We show that the population-specific distribution pattern of retrocopies is phylogenetically informative and can be used to infer population history with a better resolution than with SNP markers.     

绞股蓝种群次生代谢产物的动态及其生态学意义

利用植物生理生态学方法,研究了自然条件下不同绞股蓝Ｇｙｎｏｓｔｅｍｍａｐｅｎｔａｐｈｙｌｌｕｍ种群中黄酮类化合物和绞股蓝皂甙的动态特征及其生态学意义。结果表明：（１）同一种群的茎,叶片和枝中黄酮类化合物的绞股蓝皂甙的动态不同,在生活史的不同阶段,种群中这两类次生代谢物受茎和叶片的影响的动态不同。     

Ecological and Geographical Divergence and Interpopulation Variability of the Masu Salmon Oncorhynchus masou As Illustrated by Populations from Primorye and Sakhalin

The geographical and ecotypical differentiation of masu salmon populations is analyzed based on the study of the scale structure and other biological characteristics of fish from different rivers of Primorye and Sakhalin. The possibility of identification of different populations (during the sea life period as well) using the indicated characteristics is discussed.     

Searching for Footprints of Positive Selection in Whole-Genome SNP Data From Nonequilibrium Populations

A major goal of population genomics is to reconstruct the history of natural populations and to infer the neutral and selective scenarios that can explain the present-day polymorphism patterns. However, the separation between neutral and selective hypotheses has proven hard, mainly because both may predict similar patterns in the genome. This study focuses on the development of methods that can be used to distinguish neutral from selective hypotheses in equilibrium and nonequilibrium populations. These methods utilize a combination of statistics on the basis of the site frequency spectrum (SFS) and linkage disequilibrium (LD). We investigate the patterns of genetic variation along recombining chromosomes using a multitude of comparisons between neutral and selective hypotheses, such as selection or neutrality in equilibrium and nonequilibrium populations and recurrent selection models. We perform hypothesis testing using the classical P-value approach, but we also introduce methods from the machine-learning field. We demonstrate that the combination of SFS- and LD-based statistics increases the power to detect recent positive selection in populations that have experienced past demographic changes.GENOMES contain information related to the history of natural populations. Past neutral and selective processes may have left footprints in the genome. Recent advances in population genetics aim to understand the patterns of genetic diversity and identify events that have led to genetic adaptations. Among them, positive selection has been a focus of many recent studies (Harr et al. 2002; Kim and Stephan 2002; Glinka et al. 2003; Akey et al. 2004; Orengo and Aguadé 2004). Their goal is to (i) provide evidence of positive selection, (ii) estimate the strength and the rate of selection, and (iii) localize the targets of selection. These objectives form the basis of a long-term pursuit, which is the understanding of the molecular basis of adaptation of populations in a changing environment.Positive selection can cause genetic hitchhiking when a beneficial mutation spreads in the population (Maynard Smith and Haigh 1974). When a strongly beneficial mutation occurs and spreads in a population, linked neutral or slightly deleterious variants hitchhike with it, and their frequency increases. According to Maynard Smith and Haigh''s model, three patterns are generated locally around the position of the beneficial mutation. First, the level of variability will be reduced since standing variation of the population that is not linked to the beneficial allele vanishes, and tightly linked polymorphisms may fix (Kaplan et al. 1989; Stephan et al. 1992). Second, the site frequency spectrum (SFS), which describes the frequency of allelic variants, shifts from its neutral expectation toward rare and high-frequency derived variants (Braverman et al. 1995; Fay and Wu 2000). The third signature describes the emergence of specific linkage disequilibrium (LD) patterns around the target of positive selection, such as an elevated level of LD in the early phase of the fixation process of the beneficial mutation and a decay of LD across the selected site at the end of the selective phase (Kim and Nielsen 2004; Stephan et al. 2006).The availability of genome-wide SNP data has made possible the scanning of genomes and the identification of loci that may have been targets of recent selective events. Several approaches have been developed within the last years that can detect the molecular signatures of positive selection (Kim and Stephan 2002; Jensen et al. 2005; Nielsen et al. 2005). While the methods of Kim and Stephan (2002) and Jensen et al. (2005) are designed to analyze subgenomic SNP data, the approach of Nielsen et al. (2005) can be applied to both subgenomic and whole-genome data (reviewed in Pavlidis et al. 2008). For this reason we concentrate here on the latter procedure. This method, called SweepFinder, calculates the probability P(x) that a polymorphism of multiplicity x is linked to a beneficial mutation using a simple selective model and the SFS prior to the selective event. Then, for each location in the genome it compares a selective with a neutral model assuming independence between the SNPs, therefore calculating the composite likelihood ratio Λ. Thus, it identifies regions where the likelihood of the selective sweep is greater than that of the neutral model using the maximum value Λ_MAX of Λ.The ω-statistic, developed by Kim and Nielsen (2004), detects specific LD patterns caused by genetic hitchhiking (described above). In the study by Kim and Nielsen (2004) the maximum value of the ω-statistic was used to identify the targets of selective sweeps. Later, Jensen et al. (2007) studied its performance in separating demographic from selective scenarios. An important result by Jensen et al. (2007) is the demonstration that for demographic parameters relevant to nonequilibrium populations (such as the cosmopolitan populations of Drosophila melanogaster) the ω-statistic can distinguish between neutral and selective scenarios. This article further develops SweepFinder and the ω-statistic such that they can eventually be applied to whole-genome SNP data sets that have been collected from nonequilibrium populations. In particular, populations undergoing population-size bottlenecks are of interest as these size changes may confound the patterns of selective sweeps (Barton 1998). For this reason we use the following approach: first, we theoretically analyze the genealogies of bottlenecked populations under neutrality and show to what extent they resemble the genealogies of single hitchhiking (SHH) events. We also point out the importance of high-frequency-derived variants in the identification of selective sweeps. Second, we study the statistical properties of SweepFinder and the ω-statistic separately and in combination. As the main result, we demonstrate that the combination of these two methods (that include both SFS and LD information) increases the power for detecting recent SHH events in nonequilibrium populations, in particular when machine-learning techniques are employed. Third we analyze the performance of SweepFinder and the ω-statistic in the detection of recurrent hitchhiking (RHH) events.     

Spatial modeling of deforestation processes in the Central Peruvian Amazon

This study examines the relation between primary forest loss and landscape characteristics in the Ucayali region, Peru. Seven variables (rivers, elevation, annual precipitation, soil suitability for agriculture, population density, paved roads, and unpaved roads), were identified as potential deforestation drivers. The variables were converted into spatially explicit layers of continuous data and divided into a 9 km² grid. A multiple regression analysis was conducted to determine variable significance. Distance to paved and unpaved roads were strongly associated with deforestation, followed by distance to rivers, annual precipitation and elevation. All significant variables were negatively correlated with deforestation. Variables excluded from the model were population density and soil suitability for agriculture, suggesting that the influence of population density on forest clearing across the study area was not significant, and that deforestation activities were undertaken regardless whether soils are suitable for agriculture or not. Based on the linear regression analysis, the significant variables were selected and added to the Land Change Modeler in order to project primary forest coverage by 2025. The modeling results predict extensive deforestation along the Aguaytia River and at the forest/non-forest interface along the paved highway. The rate of primary forest removal is expected to increase from 4783 ha y⁻¹ (for the 2007–2014 period) to 5086 ha y⁻¹ (for the 2015–2025 period). A preliminary survey questionnaire conducted to explore deforestation intentions by farmers in the region, partly confirmed the overall deforestation trends as projected by the model.     

Genetic Variation and Recent Positive Selection in Worldwide Human Populations: Evidence from Nearly 1 Million SNPs

Background

Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs) have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world.

Methodology

We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations) from the Human Genome Diversity Panel (HGDP-CEPH). When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental) level.

Conclusions

Our analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO) analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature.     

Characterizing Uncertainty in High-Density Maps from Multiparental Populations

Multiparental populations are of considerable interest in high-density genetic mapping due to their increased levels of polymorphism and recombination relative to biparental populations. However, errors in map construction can have significant impact on QTL discovery in later stages of analysis, and few methods have been developed to quantify the uncertainty attached to the reported order of markers or intermarker distances. Current methods are computationally intensive or limited to assessing uncertainty only for order or distance, but not both simultaneously. We derive the asymptotic joint distribution of maximum composite likelihood estimators for intermarker distances. This approach allows us to construct hypothesis tests and confidence intervals for simultaneously assessing marker-order instability and distance uncertainty. We investigate the effects of marker density, population size, and founder distribution patterns on map confidence in multiparental populations through simulations. Using these data, we provide guidelines on sample sizes necessary to map markers at sub-centimorgan densities with high certainty. We apply these approaches to data from a bread wheat Multiparent Advanced Generation Inter-Cross (MAGIC) population genotyped using the Illumina 9K SNP chip to assess regions of uncertainty and validate them against the recently released pseudomolecule for the wheat chromosome 3B.     

Origins and genetic conservation of tropical trees in agroforestry systems: a case study from the Peruvian Amazon

Hundreds of native tree species are currently found in extensive agroforestry ecosystems in the Peruvian Amazon, forming an important reservoir of biodiversity. To further promote conservation, farmers are encouraged to supplement intra-specific genetic diversity in these populations with seed collected from local forests. For some tree species, however, this approach may be inappropriate, as stands of these taxa already found on-farm may not be of local origin. Despite this issue being of importance for conservation, little information is available on the history of cultivated trees in the region, a situation that we here rectify for the important fruit tree Inga edulis. Based on nuclear SSR and chloroplast DHPLC analyses of closely geographically matched natural and planted stands at five sites, it appears that cultivated material of I. edulis is primarily of non-local origin, indicating that conservation based on new wide-scale infusions from local wild stands into farms may be inappropriate in the region. Although nuclear and chloroplast diversity were both lower in planted stands, values were still relatively high (∼80 and 70% of natural stands, respectively), indicating that when farmers plant trees, good collection practice of seed from already cultivated I. edulis should be an effective means for ensuring long-term conservation on farms.