Positive Selection within the Schizophrenia-Associated GABA(A) Receptor β(2) Gene

The gamma-aminobutyric acid type-A (GABA(A)) receptor plays a major role in inhibitory neurotransmissions. Intronic SNPs and haplotypes in GABRB2, the gene for GABA(A) receptor β(2) subunit, are associated with schizophrenia and correlated with the expression of two alternatively spliced β(2) isoforms. In the present study, using chimpanzee as an ancestral reference, high frequencies were observed for the derived (D) alleles of the four SNPs rs6556547, rs187269, rs1816071 and rs1816072 in GABRB2, suggesting the occurrence of positive selection for these derived alleles. Coalescence-based simulation showed that the population frequency spectra and the frequencies of H56, the haplotype having all four D alleles, significantly deviated from neutral-evolution expectation in various demographic models. Haplotypes containing the derived allele of rs1816072 displayed significantly less diversity compared to haplotypes containing its ancestral allele, further supporting positive selection. The variations in DD-genotype frequencies in five human populations provided a snapshot of the evolutionary history, which suggested that the positive selections of the D alleles are recent and likely ongoing. The divergence between the DD-genotype profiles of schizophrenic and control samples pointed to the schizophrenia-relevance of positive selections, with the schizophrenic samples showing weakened selections compared to the controls. These DD-genotypes were previously found to increase the expression of β(2), especially its long isoform. Electrophysiological analysis showed that this long β(2) isoform favored by the positive selections is more sensitive than the short isoform to the inhibition of GABA(A) receptor function by energy depletion. These findings represent the first demonstration of positive selection in a schizophrenia-associated gene

Population Genetic Diversity and Phylogenetic Characteristics for High-Altitude Adaptive Kham Tibetan Revealed by DNATyperTM 19 Amplification System

Tibetans residing in the high-altitude inhospitable environment have undergone significant natural selection of their genetic architecture. Recently, highly mutational autosomal short tandem repeats were widely used not only in the anthropology and population genetics to investigate the genetic structure and relationships, but also in the medical genetics to explore the pathogenesis of multiple genetic diseases and in the forensic science to identify individual and parentage relatedness. However, genetic variants and forensic efficiency of DNATyperTM 19 amplification system and genetic background of Kham Tibetan remain uncharacterized. Thus, we genotyped 19 forensic genetic markers in 11,402 Kham Tibetans to gain insight into the genetic diversity of Chinese high-altitude adaptive population. Highly discriminating and polymorphic forensic measures were observed, which indicated that this new-developed DNATyper 19 PCR amplification is suitable for routine forensic identification purposes and Chinese national DNA database establishment. Pairwise genetic distances among the comprehensive population comparisons suggested that this high-altitude adaptive Kham Tibetan has genetically closer relationships with lowlanders of Tibeto-Burman-speaking populations (Chengdu Tibetan, Liangshan Tibetan, and Liangshan Yi). Genetic substructure analyses via phylogenetic reconstruction, principal component analysis, and multidimensional scaling analysis in both nationwide and worldwide contexts suggested that the genetic proximity exists along the linguistic, ethnic, and continental geographical boundary. Further studies with whole-genome sequencing of modern or archaic Kham Tibetans would be useful in reconstructing the Tibetan population history

Genetic consequences of Quaternary climatic oscillations in the Himalayas: Primula tibetica as a case study based on restriction site-associated DNA sequencing.

The effects of Quaternary climatic oscillations on the demography of organisms vary across regions and continents. In taxa distributed in Europe and North America, several paradigms regarding the distribution of refugia have been identified. By contrast, less is known about the processes that shaped the species' spatial genetic structure in areas such as the Himalayas, which is considered a biodiversity hotspot. Here, we investigated the phylogeographic structure and population dynamics of Primula tibetica by combining genomic phylogeography and species distribution models (SDMs). Genomic data were obtained for 293 samples of P. tibetica using restriction site-associated DNA sequencing (RADseq). Ensemble SDMs were carried out to predict potential present and past distribution ranges. Four distinct lineages were identified. Approximate Bayesian computation analyses showed that each of them have experienced both expansions and bottlenecks since their divergence, which occurred during or across the Quaternary glacial cycles. The two lineages at both edges of the distribution were found to be more vulnerable and responded in different ways to past climatic changes. These results illustrate how past climatic changes affected the demographic history of Himalayan organisms. Our findings highlight the significance of combining genomic approaches with environmental data when evaluating the effects of past climatic changes

Uurali rahvaste geneetiline ajalugu läbi isaliini N ja autosoomse varieeruvuse prisma

Väitekirja elektrooniline versioon ei sisalda publikatsiooneEuroopast Lääne-Siberini levinud uurali keelkond postuleeriti enam kui saja aasta eest. Mitme põlvkonna eri teadusvaldkondade teadlaste töö tulemusena on kogutud aukartustäratav andmestik selle keelkonna rahvaste kohta, kuid erilise huvi objektiks on jäänud küsimus nende ühisest päritolust, võimalikust algkodust ja rändeteedest, mille kohta on välja pakutud arvukalt huvitavaid hüpoteese. Eelkõige geograafiast sõltuvas isalt pojale päranduvate Y-kromosoomi variantide ehk isaliinide jaotusmustris eristub selgelt haplogrupp N, mis seob nii Euroopa kui Aasia põhjaaladel elavaid rahvaid ning iseloomustab ka suurt osa uurali keeli kõnelevatest meestest. Käesoleva doktoritöö eesmärgiks oli esiteks rakendada kaasaegseid DNA järjestustehnoloogiaid hindamaks haplogrupi N fülogeneetilise puu sisestruktuuri ja alamklaadide ekspansiooniaegu ning levikut Põhja-Euraasias. Teiseks testida uusimate statistiliste meetoditega võimaliku geneetilise ühisosa olemasolu uurali keelesugulaste vahel, tuginedes ülegenoomsetele genotüpiseerimisandmetele. Selgus, et haplogrupp N on tõenäoliselt algselt pärit Põhja-Hiinast või mandrilisest Kagu-Aasiast ning haplogrupi sisemine struktuur koosneb mitmest piiritletud geograafilise levikuga alamklaadist. Ühel neist, haplogrupi N3 alamklaad N3a3’6, mille levikuaja algus jääb umbes 5000 aasta tagusesse aega, on tähelepanuväärselt lai geograafiline levik, mis ulatub Läänemere idakaldalt kuni Mongoolia ja Vene Beringiani ning hõlmab märkimisväärse osa kõikidesse suurematesse Põhja-Euraasia keelkondadesse kuuluvatest meestest. Ülegenoomsete andmete põhjal on enamusel uurali keeli kõnelejatest piiratud, kuid tuvastatav hiljutine tõenäoliselt Siberi päritolu geneetiline ühisosa, mis vihjab keelte levikuga kaasas käinud inimeste rändele. Samas on see ühine geneetiline komponent seotud ulatuslikumate ida poolt lähtunud mõjutustega Kirde-Euroopa kaasaegsete rahvaste geenifondile, mis tõenäoliselt ei piirdunud ainult uurali keeli rääkinud inimeste sisserändega.The Uralic linguistic family has been postulated for more than a hundred years with a current distribution area spanning from Europe to West Siberia. The prehistory of Uralic languages and their speakers has been under scrutiny of several generations of scientists from a variety of scientific fields. Numerous hypotheses have been proposed regarding their common origin, dispersal routes and possible homeland, but these questions continue to remain scientifically disputable. A clear disruptor in the pattern of geography-dependent distribution of Y-chromosomal paternal lineages is haplogroup N that unites populations across entire north Eurasia and describes a fair share of Uralic-speaking males in both northeastern Europe and west Siberia. First aim of this thesis was to apply novel DNA re-sequencing approach to resolve the inner phylogenetic structure of haplogroup N and estimate coalescent ages along with geographic distribution of its inner subclades. Second aim was to test for a common autosomal genetic substrate between Uralic speakers using novel statistical methods. The results suggest hg N to initially originate from North China or Mainland Southeast Asia and contain several novel subclades with distinct phylogeographic spread. One such subclade, N3a3’6 within subhaplogroup N3, displays an expansion time of 5000 years, but has a remarkably wide geographic distribution ranging from the eastern shores of the Baltic Sea to Mongolia and Pacific Russian Beringia, encompassing a considerate fraction of men from all major linguistic families in north Eurasia. Whole genome data shows a small, yet significant autosomal genetic component of possible Siberian ancestry shared between most of the Uralic-speaking populations, suggesting a migratory contribution to the dispersal of the languages. This component is part of a broader eastern influence on the genepool of modern northern Europe and was probably not limited to the spread of extant Uralic languages.https://www.ester.ee/record=b526783

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Nuclear gene phylogeography using PHASE: dealing with unresolved genotypes, lost alleles, and systematic bias in parameter estimation

<p>Abstract</p> <p>Background</p> <p>A widely-used approach for screening nuclear DNA markers is to obtain sequence data and use bioinformatic algorithms to estimate which two alleles are present in heterozygous individuals. It is common practice to omit unresolved genotypes from downstream analyses, but the implications of this have not been investigated. We evaluated the haplotype reconstruction method implemented by PHASE in the context of phylogeographic applications. Empirical sequence datasets from five non-coding nuclear loci with gametic phase ascribed by molecular approaches were coupled with simulated datasets to investigate three key issues: (1) haplotype reconstruction error rates and the nature of inference errors, (2) dataset features and genotypic configurations that drive haplotype reconstruction uncertainty, and (3) impacts of omitting unresolved genotypes on levels of observed phylogenetic diversity and the accuracy of downstream phylogeographic analyses.</p> <p>Results</p> <p>We found that PHASE usually had very low false-positives (i.e., a low rate of confidently inferring haplotype pairs that were incorrect). The majority of genotypes that could not be resolved with high confidence included an allele occurring only once in a dataset, and genotypic configurations involving two low-frequency alleles were disproportionately represented in the pool of unresolved genotypes. The standard practice of omitting unresolved genotypes from downstream analyses can lead to considerable reductions in overall phylogenetic diversity that is skewed towards the loss of alleles with larger-than-average pairwise sequence divergences, and in turn, this causes systematic bias in estimates of important population genetic parameters.</p> <p>Conclusions</p> <p>A combination of experimental and computational approaches for resolving phase of segregating sites in phylogeographic applications is essential. We outline practical approaches to mitigating potential impacts of computational haplotype reconstruction on phylogeographic inferences. With targeted application of laboratory procedures that enable unambiguous phase determination via physical isolation of alleles from diploid PCR products, relatively little investment of time and effort is needed to overcome the observed biases.</p

Genetic and morphological analyses of historic and contemporary populations of western lowland gorilla: a multidisciplinary approach for the conservation of a critically endangered primate

This study investigates the morphology and genetic diversity of the critically endangered sub-species, the western lowland gorilla (Gorilla gorilla gorilla). Regional variation of a historic wild population was assessed morphologically and genetically, and genetic comparisons between this and a contemporary captive population were made to assess the genetic fitness of the contemporary population with the aim of assisting future conservation planning. Geometric morphometric analyses were applied to skulls and mandibles of both sexes in the historic population of gorillas to assess regional variation in relation to size and shape. No significant difference was found for regional size comparisons but shape variation between regions did find significant variation in skull morphology, particularly for males. MtDNA and nuclear markers were employed to detect regional differentiation in the historic population of gorillas, and to compare genetic diversity between historic and contemporary populations. The mtDNA results were hindered by nuclear insertions (numts) yet 30 sequences of the mitochondrial Control Region Hypervariable Region I (HVI) were obtained and haplogroups identified, which revealed potential differences in the historic distribution of haplogroups than current literature reports. Nuclear analysis based on microsatellites confirmed that all the gorillas used in this study were western lowland gorillas. Furthermore, the paternity of individuals in the contemporary population was confirmed. Comparisons between the historical population and the captive US population showed that genetic diversity of the contemporary population had been retained at similar levels to wild populations and the US captive population thus concluding that the contemporary population is genetically sustainable for the foreseeable future

Learning from the past : genetic analyses of ancient and contemporary samples identify how historic and pre-historic events have shaped modern whale populations

v, 94 leaves : ill. (some col.), map ; 29 cm.Includes abstract.Includes bibliographical references.The techniques for genetic species identification and inferring past population sizes are being utilized in more fields than just population genetics. Anthropology, conservation biology, and species management are also using these practices. They can use these techniques to confirm historical data and to make informed decisions in the future. By using genetic species identification on ancient whale bones recovered from traditional First Nations whaling sites, it was discovered that gray and humpback whales were the species of choice. This is important information in regards to the future of First Nations traditional whaling on Canada’s west coast. The DNA recovered from these ancient whale bones was then used to estimate pre-commercial whaling genetic variation, and make inferences about historic and pre-historic population demography. In addition to gaining insight into historic population demography, I also found that results differed dramatically if such inferences were based on historic or contemporary samples. These results are particularly important given the increasing popularity of using contemporary samples to infer population history, and show that caution is required when interpreting the results of such studies