A Machine-Learning-Based Approach to Prediction of Biogeographic Ancestry within Europe.

Data obtained with the use of massive parallel sequencing (MPS) can be valuable in population genetics studies. In particular, such data harbor the potential for distinguishing samples from different populations, especially from those coming from adjacent populations of common origin. Machine learning (ML) techniques seem to be especially well suited for analyzing large datasets obtained using MPS. The Slavic populations constitute about a third of the population of Europe and inhabit a large area of the continent, while being relatively closely related in population genetics terms. In this proof-of-concept study, various ML techniques were used to classify DNA samples from Slavic and non-Slavic individuals. The primary objective of this study was to empirically evaluate the feasibility of discerning the genetic provenance of individuals of Slavic descent who exhibit genetic similarity, with the overarching goal of categorizing DNA specimens derived from diverse Slavic population representatives. Raw sequencing data were pre-processed, to obtain a 1200 character-long binary vector. A total of three classifiers were used-Random Forest, Support Vector Machine (SVM), and XGBoost. The most-promising results were obtained using SVM with a linear kernel, with 99.9% accuracy and F1-scores of 0.9846-1.000 for all classes.

Mitogenomics of the Koryaks and Evens of the northern coast of the Sea of Okhotsk.

Due to the geographical proximity of the northern coast of the Sea of Okhotsk and Kamchatka Peninsula to the Beringia, the indigenous populations of these territories are of great interest for elucidating the human settlement history of northern Asia and America. Meanwhile, there is a clear shortage of genetic studies of the indigenous populations of the northern coast of the Sea of Okhotsk. Here, in order to examine their fine-scale matrilineal genetic structure, ancestry and relationships with neighboring populations, we analyzed 203 complete mitogenomes (174 of which are new) from population samples of the Koryaks and Evens of the northern coast of the Sea of Okhotsk and the Chukchi of the extreme northeast Asia. The patterns observed underscore the reduced level of genetic diversity found in the Koryak, Even, and Chukchi populations, which, along with the high degree of interpopulation differentiation, may be the result of genetic drift. Our phylogeographic analysis reveals common Paleo-Asiatic ancestry for 51.1% of the Koryaks and 17.8% of the Evens. About third of the mitogenomes found in the Koryaks and Evens might be considered as ethno-specific, as these are virtually absent elsewhere in North, Central and East Asia. Coalescence ages of most of these lineages coincide well with the emergence and development of the Tokarev and Old Koryak archaeological cultures associated with the formation of the Koryaks, as well as with the period of separation and split of the North Tungusic groups migrated northwards from the Lake Baikal or the Amur River area.

Response to Wyckelsma et al.: Loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation.

The common loss-of-function mutation R577X in the structural muscle protein ACTN3 emerged as a potential target of positive selection from early studies and has been the focus of insightful physiological work suggesting a significant impact on muscle metabolism. Adaptation to cold climates has been proposed as a key adaptive mechanism explaining its global allele frequency patterns. Here, we re-examine this hypothesis analyzing modern (n = 3,626) and ancient (n = 1,651) genomic data by using allele-frequency as well as haplotype homozygosity-based methods. The presented results are more consistent with genetic drift rather than selection in cold climates as the main driver of the ACTN3 R577X frequency distribution in human populations across the world. This Matters Arising paper is in response to Wyckelsma et al. (2021),1 published in The American Journal of Human Genetics. See also the response by Wyckelsma et al. (2022),2 published in this issue.

An association between copy number variation of enhancer involved in craniofacial development and biogeographic ancestry.

Human facial morphology is a combination of many complex traits and is determined by a large number of genes and enhancers. Here, we report a Copy Number Variation (CNV) study of enhancer hs1431 in populations of Central European and South Siberian ancestry. Central European samples included 97 Poles, while South Siberian samples included 78 Buryats and 27 Tuvinians. CNVs were detected by real-time PCR, using ViiA™ 7 Real-Time PCR System (Applied Biosystems). We revealed significant differences in CNV of hs1431 enhancer between Polish and Buryat population (p=0.0378), but not between Central European and South Siberian population (p=0.1225). Our results suggest that an increase in copy number variation of hs1431 enhancer is associated with biogeographic ancestry. However, this result needs extending and replicating in larger cohorts. This is the first study revealing the presence of copy number variation of enhancer hs1431 in humans.

Verification of insertion-deletion markers (InDels) and microsatellites (STRs) as subsidiary tools for inferring Slavic population ancestry.

Genetic markers for the prediction of biogeographical ancestry have proved to be effective tools for law enforcement agencies for many years now. In this study, we attempted to assess the potential of insertion-deletion markers (InDel) and microsatellites (STRs) as subsidiary polymorphisms for inference of Slavic population ancestry. For that purpose, we genotyped Slavic-speaking populations samples from Belarus, the Czech Republic, Poland, Serbia, Ukraine and Russia in 46 InDels and 15 STRs by PCR and capillary electrophoresis and analyzed for between-population differentiation with the use of distance-based methods (FST, principal component analysis and multidimensional scaling). Additionally, we studied a sample from a Polish individual of well-documented genealogy whose biogeographic ancestry had previously been inferred by commercial genomic services using autosomal single nucleotide polymorphisms (SNPs), mitochondrial DNA and Y-SNP markers. For comparative purposes, we used genotype data collected in the "forInDel" browser and allele frequencies from previously published papers. The results obtained for InDels and STRs show that the Slavic populations constitute a genetically homogeneous group, with the exception of the Czechs differing clearly from the other tested populations. The analysis of the known Polish sample in the Snipper application proves the usefulness of the InDel markers on the continental level only. Conversely, microsatellites not only improve prediction, but are also informative if considered as an independent set of ancestry markers.

Mitogenomics of modern Mongolic-speaking populations.

Here, we present a comprehensive data set of 489 complete mitogenomes (211 of which are new) from four Mongolic-speaking populations (Mongols, Barghuts, Khamnigans, and Buryats) to investigate their matrilineal genetic structure, ancestry and relationship with other ethnic groups. We show that along with very high levels of genetic diversity and lack of genetic differentiation, Mongolic-speaking populations exhibit strong genetic resemblance to East Asian populations of Chinese, Japanese, and Uyghurs. Phylogeographic analysis of complete mitogenomes reveals the presence of different components in the gene pools of modern Mongolic-speaking populations-the main East Eurasian component is represented by mtDNA lineages of East Asian, Siberian and autochthonous (the Baikal region/Mongolian) ancestry, whereas the less pronounced West Eurasian component can be ascribed to Europe and West Asia/Caucasus. We also observed that up to one third of the mtDNA subhaplogroups identified in Mongolic-speaking populations can be considered as Mongolic-specific with the coalescence age of most of them not exceeding 1.7 kya. This coincides well with the population size growth which started around 1.1 kya and is detectable only in the Bayesian Skyline Plot constructed based on Mongolic-specific mitogenomes. Our data suggest that the genetic structure established during the Mongol empire is still retained in present-day Mongolic-speaking populations.

Complete mitogenome data for the Serbian population: the contribution to high-quality forensic databases.

Mitochondrial genome (mtDNA) is a valuable resource in resolving various human forensic casework. The usage of variability of complete mtDNA genomes increases their discriminatory power to the maximum and enables ultimate resolution of distinct maternal lineages. However, their wider employment in forensic casework is nowadays limited by the lack of appropriate reference database. In order to fill in the gap in the reference data, which, considering Slavic-speaking populations, currently comprises only mitogenomes of East and West Slavs, we present mitogenome data for 226 Serbians, representatives of South Slavs from the Balkan Peninsula. We found 143 (sub)haplogroups among which West Eurasian ones were dominant. The percentage of unique haplotypes was 85%, and the random match probability was as low as 0.53%. We support previous findings on both high levels of genetic diversity in the Serbian population and patterns of genetic differentiation among this and ten studied European populations. However, our high-resolution data supported more pronounced genetic differentiation among Serbians and two Slavic populations (Russians and Poles) as well as expansion of the Serbian population after the Last Glacial Maximum and during the Migration period (fourth to ninth century A.D.), as inferred from the Bayesian skyline analysis. Phylogenetic analysis of haplotypes found in Serbians contributed towards the improvement of the worldwide mtDNA phylogeny, which is essential for the interpretation of the mtDNA casework.

Insights into matrilineal genetic structure, differentiation and ancestry of Armenians based on complete mitogenome data.

Distinctive peculiarities of Armenians such as their millennia-long genetic isolation and strong national identity attract a keen interest while studying the demographic history of the West Asia. Here, to examine their fine-scale matrilineal genetic structure, ancestry and relationships with neighboring populations, we analyzed 536 complete mitogenomes (141 of which are novel) from 8 geographically different Armenian populations, covering the whole stretch of historical Armenia. The observed patterns highlight a remarkable degree of matrilineal genetic heterogeneity and weak population structuring of Armenians. Moreover, our phylogeographic analysis reveals common ancestries for some mtDNA lineages shared by West Asians, Transcaucasians, Europeans, Central Asians and Armenians. About third of the mtDNA subhaplogroups found in Armenian gene pool might be considered as Armenian-specific, as these are virtually absent elsewhere in Europe, West Asia and Transcaucasia. Coalescence ages of most of these lineages do not exceed 3.1 kya and coincide well with the population size growth started around 1.8-2.8 kya detectable only in the Bayesian Skyline Plots based on the Armenian-specific mtDNA haplotypes.

Whole mitochondrial genome diversity in two Hungarian populations.

Complete mitochondrial genomics is an effective tool for studying the demographic history of human populations, but there is still a deficit of mitogenomic data in European populations. In this paper, we present results of study of variability of 80 complete mitochondrial genomes in two Hungarian populations from eastern part of Hungary (Szeged and Debrecen areas). The genetic diversity of Hungarian mitogenomes is remarkably high, reaching 99.9% in a combined sample. According to the analysis of molecular variance (AMOVA), European populations showed a low, but statistically significant level of between-population differentiation (Fst = 0.61%, p = 0), and two Hungarian populations demonstrate lack of between-population differences. Phylogeographic analysis allowed us to identify 71 different mtDNA sub-clades in Hungarians, sixteen of which are novel. Analysis of ancestry-informative mtDNA sub-clades revealed a complex genetic structure associated with the genetic impact of populations from different parts of Eurasia, though the contribution from European populations is the most pronounced. At least 8% of ancestry-informative haplotypes found in Hungarians demonstrate similarity with East and West Slavic populations (sub-clades H1c23a, H2a1c1, J2b1a6, T2b25a1, U4a2e, K1c1j, and I1a1c), while the influence of Siberian populations is not so noticeable (sub-clades A12a, C4a1a, and probably U4b1a4).

Mitogenomic diversity and differentiation of the Buryats.

In this paper we present a results of first comprehensive study of the complete mitogenomes in the Buryats with regard to their belonging to the main regional (eastern and western Buryats); tribal (Khori, Ekhirid, Bulagad, and Khongodor), and ethno-territorial (Aginsk, Alar, Balagansk, Barguzin, Ida, Khorinsk, Kuda, Selenga, Verkholensk, Olkhon, Tunka, and Shenehen Buryats) groups. The analysis of molecular variation performed using regional, tribal, and ethno-territorial divisions of the Buryats showed lack of genetic differentiation at all levels. Nonetheless, the complete mitogenome analysis revealed a very high level of genetic diversity in the Buryats which is the highest among Siberian populations and comparable to that in populations of eastern and western Asia. The AMOVA and MDS analyses results imply to a strong genetic similarity between the Buryats and eastern Asian populations of Chinese and Japanese, suggesting their origin on the basis of common maternal ancestry components. Several new Buryat-specific branches of haplogroup G (G2a2a, G2a1i, G2a5a) display signals of dispersals dating to 2.6-6.6 kya with a possible origin in eastern Asia, thus testifying Bronze Age and Neolithic arrival of ancestral eastern Asian component to the South Siberia region.

Eight Millennia of Matrilineal Genetic Continuity in the South Caucasus.

The South Caucasus, situated between the Black and Caspian Seas, geographically links Europe with the Near East and has served as a crossroad for human migrations for many millennia [1-7]. Despite a vast archaeological record showing distinct cultural turnovers, the demographic events that shaped the human populations of this region is not known [8, 9]. To shed light on the maternal genetic history of the region, we analyzed the complete mitochondrial genomes of 52 ancient skeletons from present-day Armenia and Artsakh spanning 7,800 years and combined this dataset with 206 mitochondrial genomes of modern Armenians. We also included previously published data of seven neighboring populations (n = 482). Coalescence-based analyses suggest that the population size in this region rapidly increased after the Last Glacial Maximum ca. 18 kya. We find that the lowest genetic distance in this dataset is between modern Armenians and the ancient individuals, as also reflected in both network analyses and discriminant analysis of principal components. We used approximate Bayesian computation to test five different demographic scenarios explaining the formation of the modern Armenian gene pool. Despite well documented cultural shifts in the South Caucasus across this time period, our results strongly favor a genetic continuity model in the maternal gene pool. This has implications for interpreting prehistoric migration dynamics and cultural shifts in this part of the world.

Mitogenomic diversity in Russians and Poles.

Complete mtDNA genome sequencing improves molecular resolution for distinguishing variation between individuals and populations, but there is still deficiency of mitogenomic population data. To overcome this limitation, we used Sanger-based protocol to generate complete mtDNA sequences of 376 Russian individuals from six populations of European part of Russia and 100 Polish individuals from northern Poland. Nearly complete resolution of mtDNA haplotypes was achieved - about 97% of haplotypes were unique both in Russians and Poles, and no haplotypes overlapped between them when indels were considered. While European populations showed a low, but statistically significant level of between-population differentiation (Fst=0.66%, p=0), Russians demonstrate lack of between-population differences (Fst=0.22%, p=0.15). Results of the Bayesian skyline analysis of Russian mitogenomes demonstrate not only post-Last Glacial Maximum expansion, but also rapid population growth starting from about 4.3kya (95% CI: 2.9-5.8kya), i.e. in the Bronze Age. This expansion strongly correlates with the Kurgan model established by archaeologists and confirmed by paleogeneticists.

Mitochondrial super-haplogroup U diversity in Serbians.

BACKGROUND: Available mitochondrial (mtDNA) data demonstrate genetic differentiation among South Slavs inhabiting the Balkan Peninsula. However, their resolution is insufficient to elucidate the female-specific aspects of the genetic history of South Slavs, including the genetic impact of various migrations which were rather common within the Balkans, a region having a turbulent demographic history. AIM: The aim was to thoroughly study complete mitogenomes of Serbians, a population linking westward and eastward South Slavs. SUBJECTS AND METHODS: Forty-six predominantly Serbian super-haplogroup U complete mitogenomes were analysed phylogenetically against ∼4000 available complete mtDNAs of modern and ancient Western Eurasians. RESULTS: Serbians share a number of U mtDNA lineages with Southern, Eastern-Central and North-Western Europeans. Putative Balkan-specific lineages (e.g. U1a1c2, U4c1b1, U5b3j, K1a4l and K1a13a1) and lineages shared among Serbians (South Slavs) and West and East Slavs were detected (e.g. U2e1b1, U2e2a1d, U4a2a, U4a2c, U4a2g1, U4d2b and U5b1a1). CONCLUSION: The exceptional diversity of maternal lineages found in Serbians may be associated with the genetic impact of both autochthonous pre-Slavic Balkan populations whose mtDNA gene pool was affected by migrations of various populations over time (e.g. Bronze Age pastoralists) and Slavic and Germanic newcomers in the early Middle Ages.

Selective sweep on human amylase genes postdates the split with Neanderthals.

Humans have more copies of amylase genes than other primates. It is still poorly understood, however, when the copy number expansion occurred and whether its spread was enhanced by selection. Here we assess amylase copy numbers in a global sample of 480 high coverage genomes and find that regions flanking the amylase locus show notable depression of genetic diversity both in African and non-African populations. Analysis of genetic variation in these regions supports the model of an early selective sweep in the human lineage after the split of humans from Neanderthals which led to the fixation of multiple copies of AMY1 in place of a single copy. We find evidence of multiple secondary losses of copy number with the highest frequency (52%) of a deletion of AMY2A and associated low copy number of AMY1 in Northeast Siberian populations whose diet has been low in starch content.

East Eurasian ancestry in the middle of Europe: genetic footprints of Steppe nomads in the genomes of Belarusian Lipka Tatars.

Medieval era encounters of nomadic groups of the Eurasian Steppe and largely sedentary East Europeans had a variety of demographic and cultural consequences. Amongst these outcomes was the emergence of the Lipka Tatars-a Slavic-speaking Sunni-Muslim minority residing in modern Belarus, Lithuania and Poland, whose ancestors arrived in these territories via several migration waves, mainly from the Golden Horde. Our results show that Belarusian Lipka Tatars share a substantial part of their gene pool with Europeans as indicated by their Y-chromosomal, mitochondrial and autosomal DNA variation. Nevertheless, Belarusian Lipkas still retain a strong genetic signal of their nomadic ancestry, witnessed by the presence of common Y-chromosomal and mitochondrial DNA variants as well as autosomal segments identical by descent between Lipkas and East Eurasians from temperate and northern regions. Hence, we document Lipka Tatars as a unique example of former Medieval migrants into Central Europe, who became sedentary, changed language to Slavic, yet preserved their faith and retained, both uni- and bi-parentally, a clear genetic echo of a complex population interplay throughout the Eurasian Steppe Belt, extending from Central Europe to northern China.

Y chromosome haplotype diversity in Mongolic-speaking populations and gene conversion at the duplicated STR DYS385a,b in haplogroup C3-M407.

Y chromosome microsatellite (Y-STR) diversity has been studied in different Mongolic-speaking populations from South Siberia, Mongolia, North-East China and East Europe. The results obtained indicate that the Mongolic-speaking populations clustered into two groups, with one group including populations from eastern part of South Siberia and Central Asia (the Buryats, Barghuts and Khamnigans) and the other group including populations from western part of Central Asia and East Europe (the Mongols and Kalmyks). High frequency of haplogroup C3-M407 (>50%) is present in the Buryats, Barghuts and Khamnigans, whereas in the Mongols and Kalmyks its frequency is much lower. In addition, two allelic combinations in DYS385a,b loci of C3-M407 haplotypes have been observed: the combination 11,18 (as well as 11,17 and 11,19) is frequent in different Mongolic-speaking populations, but the 11,11 branch is present mainly in the Kalmyks and Mongols. Results of locus-specific sequencing suggest that the action of gene conversion is a more likely explanation for origin of homoallelic 11,11 combination. Moreover, analysis of median networks of Y-STR haplotypes demonstrates that at least two gene conversion events can be revealed-one of them has probably occurred among the Mongols, and the other event occurred in the Barghuts. These two events give an average gene conversion rate range of 0.24-7.1 × 10(-3) per generation.

The genetic legacy of the expansion of Turkic-speaking nomads across Eurasia.

The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic languages. These groups have dispersed across a vast area, including Siberia, Northwest China, Central Asia, East Europe, the Caucasus, Anatolia, the Middle East, and Afghanistan. The origin and early dispersal history of the Turkic peoples is disputed, with candidates for their ancient homeland ranging from the Transcaspian steppe to Manchuria in Northeast Asia. Previous genetic studies have not identified a clear-cut unifying genetic signal for the Turkic peoples, which lends support for language replacement rather than demic diffusion as the model for the Turkic language's expansion. We addressed the genetic origin of 373 individuals from 22 Turkic-speaking populations, representing their current geographic range, by analyzing genome-wide high-density genotype data. In agreement with the elite dominance model of language expansion most of the Turkic peoples studied genetically resemble their geographic neighbors. However, western Turkic peoples sampled across West Eurasia shared an excess of long chromosomal tracts that are identical by descent (IBD) with populations from present-day South Siberia and Mongolia (SSM), an area where historians center a series of early Turkic and non-Turkic steppe polities. While SSM matching IBD tracts (> 1cM) are also observed in non-Turkic populations, Turkic peoples demonstrate a higher percentage of such tracts (p-values ≤ 0.01) compared to their non-Turkic neighbors. Finally, we used the ALDER method and inferred admixture dates (~9th-17th centuries) that overlap with the Turkic migrations of the 5th-16th centuries. Thus, our results indicate historical admixture among Turkic peoples, and the recent shared ancestry with modern populations in SSM supports one of the hypothesized homelands for their nomadic Turkic and related Mongolic ancestors.

Mitochondrial DNA perspective of Serbian genetic diversity.

Although south-Slavic populations have been studied to date from various aspects, the population of Serbia, occupying the central part of the Balkan Peninsula, is still genetically understudied at least at the level of mitochondrial DNA (mtDNA) variation. We analyzed polymorphisms of the first and the second mtDNA hypervariable segments (HVS-I and HVS-II) and informative coding-region markers in 139 Serbians to shed more light on their mtDNA variability, and used available data on other Slavic and neighboring non-Slavic populations to assess their interrelations in a broader European context. The contemporary Serbian mtDNA profile is consistent with the general European maternal landscape having a substantial proportion of shared haplotypes with eastern, central, and southern European populations. Serbian population was characterized as an important link between easternmost and westernmost south-Slavic populations due to the observed lack of genetic differentiation with all other south-Slavic populations and its geographical positioning within the Balkan Peninsula. An increased heterogeneity of south Slavs, most likely mirroring turbulent demographic events within the Balkan Peninsula over time (i.e., frequent admixture and differential introgression of various gene pools), and a marked geographical stratification of Slavs to south-, east-, and west-Slavic groups, were also found. A phylogeographic analyses of 20 completely sequenced Serbian mitochondrial genomes revealed not only the presence of mtDNA lineages predominantly found within the Slavic gene pool (U4a2a*, U4a2a1, U4a2c, U4a2g, HV10), supporting a common Slavic origin, but also lineages that may have originated within the southern Europe (H5*, H5e1, H5a1v) and the Balkan Peninsula in particular (H6a2b and L2a1k).

Simple and cost-effective 14-loci SNP assay designed for differentiation of European, East Asian and African samples.

During every criminal investigation, it is vital to extract as much information as possible from every piece of evidence. When it comes to DNA testing, simple short tandem repeat (STR) typing may soon become a relic because it is now possible to genotype more characteristics. Ancestry informative markers are receiving attention from the forensic community because individuals can be assigned to their population or territory of origin based on their analysis. Many panels of this kind have been proposed so far, yet most of them require typing of a large number of loci. In many cases it is crucial to pick a minimal set of the most informative markers due to the limited amount of material available for analysis. In this study, we demonstrate that 14 carefully picked SNPs combined in two multiplex assays are capable of fast, robust and cost effective three-way differentiation of East Asians, Europeans and Africans.