Population mixture is an important process in biology. We present a suite of methods for learning about population mixtures, implemented in a software package called ADMIXTOOLS, that support formal tests for whether mixture occurred and make it possible to infer proportions and dates of mixture. We also describe the development of a new single nucleotide polymorphism (SNP) array consisting of 629,433 sites with clearly documented ascertainment that was specifically designed for population genetic analyses and that we genotyped in 934 individuals from 53 diverse populations. To illustrate the methods, we give a number of examples that provide new insights about the history of human admixture. The most striking finding is a clear signal of admixture into northern Europe, with one ancestral population related to present-day Basques and Sardinians and the other related to present-day populations of northeast Asia and the Americas. This likely reflects a history of admixture between Neolithic migrants and the indigenous Mesolithic population of Europe, consistent with recent analyses of ancient bones from Sweden and the sequencing of the genome of the Tyrolean "Iceman."

https://www.genetics.org/content/genetics/192/3/1065.full.pdf

Ancient Admixture in Human History

High-throughput DNA sequencing technologies are generating vast amounts of data. Fast, flexible and memory efficient implementations are needed in order to facilitate analyses of thousands of samples simultaneously. We present a multithreaded program suite called ANGSD. This program can calculate various summary statistics, and perform association mapping and population genetic analyses utilizing the full information in next generation sequencing data by working directly on the raw sequencing data or by using genotype likelihoods. The open source c/c++ program ANGSD is available at http://www.popgen.dk/angsd
 . The program is tested and validated on GNU/Linux systems. The program facilitates multiple input formats including BAM and imputed beagle genotype probability files. The program allow the user to choose between combinations of existing methods and can perform analysis that is not implemented elsewhere.

/pdf/angsd-analysis-of-next-generation-sequencing-data-5asmh9loag.pdf

ANGSD: Analysis of Next Generation Sequencing Data

Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

Environment dominates over host genetics in shaping human gut microbiota

Human mitochondrial DNA is widely used as tool in many fields including evolutionary anthropology and population history, medical genetics, genetic genealogy, and forensic science. Many applications require detailed knowledge about the phylogenetic relationship of mtDNA variants. Although the phylogenetic resolution of global human mtDNA diversity has greatly improved as a result of increasing sequencing efforts of complete mtDNA genomes, an updated overall mtDNA tree is currently not available. In order to facilitate a better use of known mtDNA variation, we have constructed an updated comprehensive phylogeny of global human mtDNA variation, based on both coding- and control region mutations. This complete mtDNA tree includes previously published as well as newly identified haplogroups, is easily navigable, will be continuously and regularly updated in the future, and is online available at http://www.phylotree.org. © 2008 Wiley-Liss, Inc.

/pdf/updated-comprehensive-phylogenetic-tree-of-global-human-448qrnrzdo.pdf

Updated Comprehensive Phylogenetic Tree of Global Human Mitochondrial DNA Variation

Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies.

/pdf/the-genetic-structure-and-history-of-africans-and-african-2v92ur94km.pdf

The Genetic Structure and History of Africans and African Americans

We studied the Y-chromosome pool of the ethnic Russian population of Novgorod oblast (Russia) by 49 SNP and 17 STR markers. The total sample (N = 191) consists of four populations of the Novgorod region, including its southwestern (Shelon Pyatina) and eastern (Bezhetsk Pyatina) parts. Altogether, these four populations represent both the area of the Sopki archaeological culture (supposedly linked with the Novgorod Slovens tribe known from the chronicles) and the area of the Long Barrows culture (supposedly linked with the Krivichi Slavic tribe or with Balts). The pronounced genetic differences between southern and northern Russian populations are well known from previous studies; however, the Novgorod gene pool turned out to be neither northern nor southern, but a representative of the intermediate buffer zone. This zone was identified in this study and included a set of regional Russian populations from Pskov in the west to Kostroma in the east. All four studied populations of Novgorod region are genetically similar. The minor differences among them might represent the medieval Slavic migrations along the rivers, which survived despite the massive demographic shifts during the following history. Haplogroup N3 comprises one-fifth of the Novgorod pool of paternal lineages, with conditionally “Finnic” N3a4 and conditionally “East Baltic Sea Coast” N3a3 clades being almost equally frequent. The N3a3 phylogenetic network revealed the specific “Balto-Slavic” cluster of STR haplotypes, which is frequent in Baltic-speaking Lithuanians but infrequent in Finno-Ugric speaking Estonians. The Novgorod haplotypes lie outside this cluster, indicating that the Novgorod population received both N3a3 and N3a4 from Finno-Ugric speaking populations of the region, which, in turn, acquired the Mesolithic gene pool of the Northeastern Europe.

Gene pool of the Novgorod population: Between the north and the south

The indigenous populations of Udmurtia (five populations of Udmurts and Besermyans) have been studied for the first time by the genome-wide array. The populations were studied in the context of all Finno-Ugric and other surrounding ethnic groups. The total analyzed dataset included 728 individual genomes from 76 populations. The ADMIXTURE analysis of ancestral components identified the specific “Udmurt” component comprising nearby 100 % of genomes of all studied Udmurt individuals and the lion’s share of genomes of the studied Besermyans. The second component in Besermyan was the “White Sea” one predominating in Komi Zyryans and northernmost populations of ethnic Russians. The three independent methods - ADMIXTURE, F, and PCA - demonstrated that Udmurts and Besermyans are genetically closest to Komi-Permyaks, followed by Mari, Chuvash, Bashkirs, and Volga Tatars. We also characterized the pharmacogenetic status of Udmurtia population by estimating frequencies of 45 pharmacogenetic markers. The cartographic analysis revealed that genetic markers used in pharmacogenetic recommendations were observed in Besermyan and Udmurt populations at frequencies close to the frequencies in indigenous groups from Volga-Ural region but not from the more remote regions. Thus, within the revealed area of genetic similarity the same pharmacogenetic protocols can be applied. Here we publish the maps of distribution of the “Udmurt” ancestral components in the area of European Russia and Ural. The maps can be used by scholars in humanitarian fields in their own studies to trace genetically the interactions of Udmurts and Besermyans with other ethnic groups.

Gene pools of udmurts and besermyans in the context of finno-ugric and other neighboring ethnic groups: the genome-wide and pharmacogenetic data

In contrast with the traditional methods applied to assessment of population diversity, high-throughput sequencing technologies have a wider application in clinical practice with greater potential to find novel disease-causing variants for multifactorial disorders. Widely used test panels may not meet their goal to diagnose the patient’s condition with a full reliability since this method often does not take into account the population frequencies of analyzed genetic markers. Here, we analyzed 57 male individuals of five ethnic groups from Russia and Tajikistan using the whole exome sequencing technique (Ion AmpliSeq Exome), which resulted in detecting more than 299,000 single nucleotide polymorphisms. Samples formed clusters on the PCA plot according to the geographical location of the corresponding populations. Thereby, the methodology of whole-exome sequencing, in general, and the Ion AmpliSeq Exome panel, in particular, could be positively applied for the purposes of population genetics and for detection of the novel clinically relevant variants.

Lessons from the Whole Exome Sequencing Effort in Populations of Russia and Tajikistan

Comments on the Caucasian Substrate Hypothesis

/pdf/gene-pool-of-three-eastern-tuvan-clans-according-to-y-2fcc4dzz5u.pdf

Oleg Balanovsky

Papers

Gene pool of the Novgorod population: Between the north and the south

Gene pools of udmurts and besermyans in the context of finno-ugric and other neighboring ethnic groups: the genome-wide and pharmacogenetic data

Lessons from the Whole Exome Sequencing Effort in Populations of Russia and Tajikistan

Comments on the Caucasian Substrate Hypothesis

Gene pool of three Eastern Tuvan clans according to Y-chromosome polymorphism