The western and eastern roots of the Saami--the story of genetic "outliers" told by mitochondrial DNA and Y chromosomes

The Saami are regarded as extreme genetic outliers among European populations. In this study, a high-resolution phylogenetic analysis of Saami genetic heritage was undertaken in a comprehensive context, through use of maternally inherited mitochondrial DNA (mtDNA) and paternally inherited Y-chromosomal variation. DNA variants present in the Saami were compared with those found in Europe and Siberia, through use of both new and previously published data from 445 Saami and 17,096 western Eurasian and Siberian mtDNA samples, as well as 127 Saami and 2,840 western Eurasian and Siberian Y-chromosome samples. It was shown that the “Saami motif” variant of mtDNA haplogroup U5b is present in a large area outside Scandinavia. A detailed phylogeographic analysis of one of the predominant Saami mtDNA haplogroups, U5b1b, which also includes the lineages of the “Saami motif,” was undertaken in 31 populations. The results indicate that the origin of U5b1b, as for the other predominant Saami haplogroup, V, is most likely in western, rather than eastern, Europe. Furthermore, an additional haplogroup (H1) spread among the Saami was virtually absent in 781 Samoyed and Ob-Ugric Siberians but was present in western and central European populations. The Y-chromosomal variety in the Saami is also consistent with their European ancestry. It suggests that the large genetic separation of the Saami from other Europeans is best explained by assuming that the Saami are descendants of a narrow, distinctive subset of Europeans. In particular, no evidence of a significant directional gene flow from extant aboriginal Siberian populations into the haploid gene pools of the Saami was found.     

Genetic Diversity among Ancient Nordic Populations

Using established criteria for work with fossil DNA we have analysed mitochondrial DNA from 92 individuals from 18 locations in Denmark ranging in time from the Mesolithic to the Medieval Age. Unequivocal assignment of mtDNA haplotypes was possible for 56 of the ancient individuals; however, the success rate varied substantially between sites; the highest rates were obtained with untouched, freshly excavated material, whereas heavy handling, archeological preservation and storage for many years influenced the ability to obtain authentic endogenic DNA. While the nucleotide diversity at two locations was similar to that among extant Danes, the diversity at four sites was considerably higher. This supports previous observations for ancient Britons. The overall occurrence of haplogroups did not deviate from extant Scandinavians, however, haplogroup I was significantly more frequent among the ancient Danes (average 13%) than among extant Danes and Scandinavians (∼2.5%) as well as among other ancient population samples reported. Haplogroup I could therefore have been an ancient Southern Scandinavian type “diluted” by later immigration events. Interestingly, the two Neolithic samples (4,200 YBP, Bell Beaker culture) that were typed were haplogroup U4 and U5a, respectively, and the single Bronze Age sample (3,300–3,500 YBP) was haplogroup U4. These two haplogroups have been associated with the Mesolithic populations of Central and Northern Europe. Therefore, at least for Southern Scandinavia, our findings do not support a possible replacement of a haplogroup U dominated hunter-gatherer population by a more haplogroup diverse Neolithic Culture.     

Indian Signatures in the Westernmost Edge of the European Romani Diaspora: New Insight from Mitogenomes

In agreement with historical documentation, several genetic studies have revealed ancestral links between the European Romani and India. The entire mitochondrial DNA (mtDNA) of 27 Spanish Romani was sequenced in order to shed further light on the origins of this population. The data were analyzed together with a large published dataset (mainly hypervariable region I [HVS-I] haplotypes) of Romani (N = 1,353) and non-Romani worldwide populations (N>150,000). Analysis of mitogenomes allowed the characterization of various Romani-specific clades. M5a1b1a1 is the most distinctive European Romani haplogroup; it is present in all Romani groups at variable frequencies (with only sporadic findings in non-Romani) and represents 18% of their mtDNA pool. Its phylogeographic features indicate that M5a1b1a1 originated 1.5 thousand years ago (kya; 95% CI: 1.3–1.8) in a proto-Romani population living in Northwest India. U3 represents the most characteristic Romani haplogroup of European/Near Eastern origin (12.4%); it appears at dissimilar frequencies across the continent (Iberia: ∼31%; Eastern/Central Europe: ∼13%). All U3 mitogenomes of our Iberian Romani sample fall within a new sub-clade, U3b1c, which can be dated to 0.5 kya (95% CI: 0.3–0.7); therefore, signaling a lower bound for the founder event that followed admixture in Europe/Near East. Other minor European/Near Eastern haplogroups (e.g. H24, H88a) were also assimilated into the Romani by introgression with neighboring populations during their diaspora into Europe; yet some show a differentiation from the phylogenetically closest non-Romani counterpart. The phylogeny of Romani mitogenomes shows clear signatures of low effective population sizes and founder effects. Overall, these results are in good agreement with historical documentation, suggesting that cultural identity and relative isolation have allowed the Romani to preserve a distinctive mtDNA heritage, with some features linking them unequivocally to their ancestral Indian homeland.     

Mitogenomes from Two Uncommon Haplogroups Mark Late Glacial/Postglacial Expansions from the Near East and Neolithic Dispersals within Europe

The current human mitochondrial (mtDNA) phylogeny does not equally represent all human populations but is biased in favour of representatives originally from north and central Europe. This especially affects the phylogeny of some uncommon West Eurasian haplogroups, including I and W, whose southern European and Near Eastern components are very poorly represented, suggesting that extensive hidden phylogenetic substructure remains to be uncovered. This study expanded and re-analysed the available datasets of I and W complete mtDNA genomes, reaching a comprehensive 419 mitogenomes, and searched for precise correlations between the ages and geographical distributions of their numerous newly identified subclades with events of human dispersal which contributed to the genetic formation of modern Europeans. Our results showed that haplogroups I (within N1a1b) and W originated in the Near East during the Last Glacial Maximum or pre-warming period (the period of gradual warming between the end of the LGM, ∼19 ky ago, and the beginning of the first main warming phase, ∼15 ky ago) and, like the much more common haplogroups J and T, may have been involved in Late Glacial expansions starting from the Near East. Thus our data contribute to a better definition of the Late and postglacial re-peopling of Europe, providing further evidence for the scenario that major population expansions started after the Last Glacial Maximum but before Neolithic times, but also evidencing traces of diffusion events in several I and W subclades dating to the European Neolithic and restricted to Europe.     

Mitochondrial Haplogroup U5b3: A Distant Echo of the Epipaleolithic in Italy and the Legacy of the Early Sardinians

There are extensive data indicating that some glacial refuge zones of southern Europe (Franco-Cantabria, Balkans, and Ukraine) were major genetic sources for the human recolonization of the continent at the beginning of the Holocene. Intriguingly, there is no genetic evidence that the refuge area located in the Italian Peninsula contributed to this process. Here we show, through phylogeographic analyses of mitochondrial DNA (mtDNA) variation performed at the highest level of molecular resolution (52 entire mitochondrial genomes), that the most likely homeland for U5b3—a haplogroup present at a very low frequency across Europe—was the Italian Peninsula. In contrast to mtDNA haplogroups that expanded from other refugia, the Holocene expansion of haplogroup U5b3 toward the North was restricted by the Alps and occurred only along the Mediterranean coasts, mainly toward nearby Provence (southern France). From there, ∼7,000–9,000 years ago, a subclade of this haplogroup moved to Sardinia, possibly as a result of the obsidian trade that linked the two regions, leaving a distinctive signature in the modern people of the island. This scenario strikingly matches the age, distribution, and postulated geographic source of a Sardinian Y chromosome haplogroup (I2a2-M26), a paradigmatic case in the European context of a founder event marking both female and male lineages.     

Between the Baltic and Danubian Worlds: The Genetic Affinities of a Middle Neolithic Population from Central Poland

For a long time, anthropological and genetic research on the Neolithic revolution in Europe was mainly concentrated on the mechanism of agricultural dispersal over different parts of the continent. Recently, attention has shifted towards population processes that occurred after the arrival of the first farmers, transforming the genetically very distinctive early Neolithic Linear Pottery Culture (LBK) and Mesolithic forager populations into present-day Central Europeans. The latest studies indicate that significant changes in this respect took place within the post-Linear Pottery cultures of the Early and Middle Neolithic which were a bridge between the allochthonous LBK and the first indigenous Neolithic culture of north-central Europe—the Funnel Beaker culture (TRB). The paper presents data on mtDNA haplotypes of a Middle Neolithic population dated to 4700/4600–4100/4000 BC belonging to the Brześć Kujawski Group of the Lengyel culture (BKG) from the Kuyavia region in north-central Poland. BKG communities constituted the border of the “Danubian World” in this part of Europe for approx. seven centuries, neighboring foragers of the North European Plain and the southern Baltic basin. MtDNA haplogroups were determined in 11 individuals, and four mtDNA macrohaplogroups were found (H, U5, T, and HV0). The overall haplogroup pattern did not deviate from other post-Linear Pottery populations from central Europe, although a complete lack of N1a and the presence of U5a are noteworthy. Of greatest importance is the observed link between the BKG and the TRB horizon, confirmed by an independent analysis of the craniometric variation of Mesolithic and Neolithic populations inhabiting central Europe. Estimated phylogenetic pattern suggests significant contribution of the post-Linear BKG communities to the origin of the subsequent Middle Neolithic cultures, such as the TRB.     

Mitochondrial DNA phylogeny in Eastern and Western Slavs

To resolve the phylogeny of certain mitochondrial DNA (mtDNA) haplogroups in eastern Europe and estimate their evolutionary age, a total of 73 samples representing mitochondrial haplogroups U4, HV*, and R1 were selected for complete mitochondrial genome sequencing from a collection of about 2,000 control region sequences sampled in eastern (Russians, Belorussians, and Ukrainians) and western (Poles, Czechs, and Slovaks) Slavs. On the basis of whole-genome resolution, we fully characterized a number of haplogroups (HV3, HV4, U4a1, U4a2, U4a3, U4b, U4c, U4d, and R1a) that were previously described only partially. Our findings demonstrate that haplogroups HV3, HV4, and U4a1 could be traced back to the pre-Neolithic times ( approximately 12,000-19,000 years before present [YBP]) in eastern Europe. In addition, an ancient connection between the Caucasus/Europe and India has been revealed by analysis of haplogroup R1 diversity, with a split between the Indian and Caucasus/European R1a lineages occurring about 16,500 years ago. Meanwhile, some mtDNA subgroups detected in Slavs (such as U4a2a, U4a2*, HV3a, and R1a1) are definitely younger being dated between 6,400 and 8,200 YBP. However, robust age estimations appear to be problematic due to the high ratios of nonsynonymous to synonymous substitutions found in young mtDNA subclusters.     

The First Modern Human Dispersals across Africa

The emergence of more refined chronologies for climate change and archaeology in prehistoric Africa, and for the evolution of human mitochondrial DNA (mtDNA), now make it feasible to test more sophisticated models of early modern human dispersals suggested by mtDNA distributions. Here we have generated 42 novel whole-mtDNA genomes belonging to haplogroup L0, the most divergent clade in the maternal line of descent, and analysed them alongside the growing database of African lineages belonging to L0’s sister clade, L1’6. We propose that the last common ancestor of modern human mtDNAs (carried by “mitochondrial Eve”) possibly arose in central Africa ~180 ka, at a time of low population size. By ~130 ka two distinct groups of anatomically modern humans co-existed in Africa: broadly, the ancestors of many modern-day Khoe and San populations in the south and a second central/eastern African group that includes the ancestors of most extant worldwide populations. Early modern human dispersals correlate with climate changes, particularly the tropical African “megadroughts” of MIS 5 (marine isotope stage 5, 135–75 ka) which paradoxically may have facilitated expansions in central and eastern Africa, ultimately triggering the dispersal out of Africa of people carrying haplogroup L3 ~60 ka. Two south to east migrations are discernible within haplogroup LO. One, between 120 and 75 ka, represents the first unambiguous long-range modern human dispersal detected by mtDNA and might have allowed the dispersal of several markers of modernity. A second one, within the last 20 ka signalled by L0d, may have been responsible for the spread of southern click-consonant languages to eastern Africa, contrary to the view that these eastern examples constitute relicts of an ancient, much wider distribution.     

Ancient DNA Reveals Matrilineal Continuity in Present-Day Poland over the Last Two Millennia

While numerous ancient human DNA datasets from across Europe have been published till date, modern-day Poland in particular, remains uninvestigated. Besides application in the reconstruction of continent-wide human history, data from this region would also contribute towards our understanding of the history of the Slavs, whose origin is hypothesized to be in East or Central Europe. Here, we present the first population-scale ancient human DNA study from the region of modern-day Poland by establishing mitochondrial DNA profiles for 23 samples dated to 200 BC – 500 AD (Roman Iron Age) and for 20 samples dated to 1000–1400 AD (Medieval Age). Our results show that mitochondrial DNA sequences from both periods belong to haplogroups that are characteristic of contemporary West Eurasia. Haplotype sharing analysis indicates that majority of the ancient haplotypes are widespread in some modern Europeans, including Poles. Notably, the Roman Iron Age samples share more rare haplotypes with Central and Northeast Europeans, whereas the Medieval Age samples share more rare haplotypes with East-Central and South-East Europeans, primarily Slavic populations. Our data demonstrates genetic continuity of certain matrilineages (H5a1 and N1a1a2) in the area of present-day Poland from at least the Roman Iron Age until present. As such, the maternal gene pool of present-day Poles, Czechs and Slovaks, categorized as Western Slavs, is likely to have descended from inhabitants of East-Central Europe during the Roman Iron Age.     

Genetic Evidence of an East Asian Origin and Paleolithic Northward Migration of Y-chromosome Haplogroup N

The Y-chromosome haplogroup N-M231 (Hg N) is distributed widely in eastern and central Asia, Siberia, as well as in eastern and northern Europe. Previous studies suggested a counterclockwise prehistoric migration of Hg N from eastern Asia to eastern and northern Europe. However, the root of this Y chromosome lineage and its detailed dispersal pattern across eastern Asia are still unclear. We analyzed haplogroup profiles and phylogeographic patterns of 1,570 Hg N individuals from 20,826 males in 359 populations across Eurasia. We first genotyped 6,371 males from 169 populations in China and Cambodia, and generated data of 360 Hg N individuals, and then combined published data on 1,210 Hg N individuals from Japanese, Southeast Asian, Siberian, European and Central Asian populations. The results showed that the sub-haplogroups of Hg N have a distinct geographical distribution. The highest Y-STR diversity of the ancestral Hg N sub-haplogroups was observed in the southern part of mainland East Asia, and further phylogeographic analyses supports an origin of Hg N in southern China. Combined with previous data, we propose that the early northward dispersal of Hg N started from southern China about 21 thousand years ago (kya), expanding into northern China 12–18 kya, and reaching further north to Siberia about 12–14 kya before a population expansion and westward migration into Central Asia and eastern/northern Europe around 8.0–10.0 kya. This northward migration of Hg N likewise coincides with retreating ice sheets after the Last Glacial Maximum (22–18 kya) in mainland East Asia.     

The Expanded mtDNA Phylogeny of the Franco-Cantabrian Region Upholds the Pre-Neolithic Genetic Substrate of Basques

The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ∼10,000 years before present (YBP), with signals of expansions at ∼3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈15%) of the Franco-Cantabrian maternal gene pool with a putative pre-Neolithic origin to ≈35%, further supporting the notion of a predominant Paleolithic genetic substrate in extant European populations.     

Evaluation of Group Genetic Ancestry of Populations from Philadelphia and Dakar in the Context of Sex-Biased Admixture in the Americas

Background

Population history can be reflected in group genetic ancestry, where genomic variation captured by the mitochondrial DNA (mtDNA) and non-recombining portion of the Y chromosome (NRY) can separate female- and male-specific admixture processes. Genetic ancestry may influence genetic association studies due to differences in individual admixture within recently admixed populations like African Americans.

Principal Findings

We evaluated the genetic ancestry of Senegalese as well as European Americans and African Americans from Philadelphia. Senegalese mtDNA consisted of ∼12% U haplotypes (U6 and U5b1b haplotypes, common in North Africa) while the NRY haplotypes belonged solely to haplogroup E. In Philadelphia, we observed varying degrees of admixture. While African Americans have 9–10% mtDNAs and ∼31% NRYs of European origin, these results are not mirrored in the mtDNA/NRY pools of European Americans: they have less than 7% mtDNAs and less than 2% NRYs from non-European sources. Additionally, there is <2% Native American contribution to Philadelphian African American ancestry and the admixture from combined mtDNA/NRY estimates is consistent with the admixture derived from autosomal genetic data. To further dissect these estimates, we have analyzed our samples in the context of different demographic groups in the Americas.

Conclusions

We found that sex-biased admixture in African-derived populations is present throughout the Americas, with continual influence of European males, while Native American females contribute mainly to populations of the Caribbean and South America. The high non-European female contribution to the pool of European-derived populations is consistently characteristic of Iberian colonization. These data suggest that genomic data correlate well with historical records of colonization in the Americas.     

Tracing past human male movements in northern/eastern Africa and western Eurasia: new clues from Y-chromosomal haplogroups E-M78 and J-M12

Detailed population data were obtained on the distribution of novel biallelic markers that finely dissect the human Y-chromosome haplogroup E-M78. Among 6,501 Y chromosomes sampled in 81 human populations worldwide, we found 517 E-M78 chromosomes and assigned them to 10 subhaplogroups. Eleven microsatellite loci were used to further evaluate subhaplogroup internal diversification. The geographic and quantitative analyses of haplogroup and microsatellite diversity is strongly suggestive of a northeastern African origin of E-M78, with a corridor for bidirectional migrations between northeastern and eastern Africa (at least 2 episodes between 23.9-17.3 ky and 18.0-5.9 ky ago), trans-Mediterranean migrations directly from northern Africa to Europe (mainly in the last 13.0 ky), and flow from northeastern Africa to western Asia between 20.0 and 6.8 ky ago. A single clade within E-M78 (E-V13) highlights a range expansion in the Bronze Age of southeastern Europe, which is also detected by haplogroup J-M12. Phylogeography pattern of molecular radiation and coalescence estimates for both haplogroups are similar and reveal that the genetic landscape of this region is, to a large extent, the consequence of a recent population growth in situ rather than the result of a mere flow of western Asian migrants in the early Neolithic. Our results not only provide a refinement of previous evolutionary hypotheses but also well-defined time frames for past human movements both in northern/eastern Africa and western Eurasia.     

Revised Timeline and Distribution of the Earliest Diverged Human Maternal Lineages in Southern Africa

The oldest extant human maternal lineages include mitochondrial haplogroups L0d and L0k found in the southern African click-speaking forager peoples broadly classified as Khoesan. Profiling these early mitochondrial lineages allows for better understanding of modern human evolution. In this study, we profile 77 new early-diverged complete mitochondrial genomes and sub-classify another 105 L0d/L0k individuals from southern Africa. We use this data to refine basal phylogenetic divergence, coalescence times and Khoesan prehistory. Our results confirm L0d as the earliest diverged lineage (∼172 kya, 95%CI: 149–199 kya), followed by L0k (∼159 kya, 95%CI: 136–183 kya) and a new lineage we name L0g (∼94 kya, 95%CI: 72–116 kya). We identify two new L0d1 subclades we name L0d1d and L0d1c4/L0d1e, and estimate L0d2 and L0d1 divergence at ∼93 kya (95%CI:76–112 kya). We concur the earliest emerging L0d1’2 sublineage L0d1b (∼49 kya, 95%CI:37–58 kya) is widely distributed across southern Africa. Concomitantly, we find the most recent sublineage L0d2a (∼17 kya, 95%CI:10–27 kya) to be equally common. While we agree that lineages L0d1c and L0k1a are restricted to contemporary inland Khoesan populations, our observed predominance of L0d2a and L0d1a in non-Khoesan populations suggests a once independent coastal Khoesan prehistory. The distribution of early-diverged human maternal lineages within contemporary southern Africans suggests a rich history of human existence prior to any archaeological evidence of migration into the region. For the first time, we provide a genetic-based evidence for significant modern human evolution in southern Africa at the time of the Last Glacial Maximum at between ∼21–17 kya, coinciding with the emergence of major lineages L0d1a, L0d2b, L0d2d and L0d2a.     

Anticancer activity and toxicity of new quaternary ammonium geldanamycin derivative salts and their mixtures with potentiators

Geldanamycin (GDM) has been modified by different type neutral/acidic/basic substituents (1–7) and by quinuclidine motif (8), transformed into ammonium salts (9–13) at C(17). These compounds have been characterised by spectroscopic and x-ray methods. Derivative 8 shows better potency than GDM in MCF-7, MDA-MB-231, A549 and HeLa (IC₅₀s = 0.09–1.06 µM). Transformation of 8 into salts 9–13 reduces toxicity (by 11-fold) at attractive potency, e.g. MCF-7 cell line (IC₅₀∼2 µM). Our studies show that higher water solubility contributes to lower toxicity of salts than GDM in healthy CCD39Lu and HDF cells. The use of 13 mixtures with potentiators PEI and DOX enhanced anticancer effects from IC₅₀∼2 µM to IC₅₀∼0.5 µM in SKBR-3, SKOV-3, and PC-3 cancer cells, relative to 13. Docking studies showed that complexes between quinuclidine-bearing 8–13 and Hsp90 are stabilised by extra hydrophobic interactions between the C(17)-arms and K58 or Y61 of Hsp90.     

Evidence for multi-copy Mega-NUMTs in the human genome

The maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals. Cells without nuclear DNA, i.e. thrombocytes and hair shafts, only showed the mitotype of haplogroup (hg) V. Skin biopsies were prepared to generate ρ° cells void of mtDNA, sequencing of which resulted in a hg U4c1 mitotype. The position of the Mega-NUMT sequence was determined by fluorescence in situ hybridization and two different quantitative PCR assays were used to determine the number of contributing mtDNA copies. Thus, evidence for the presence of repetitive, full mitogenome Mega-NUMTs matching haplogroup U4c1 in various tissues of eight maternally related individuals was provided. Multi-copy Mega-NUMTs mimic mixtures of mtDNA that cannot be experimentally avoided and thus may appear in diverse fields of mtDNA research and diagnostics. We demonstrate that hair shaft mtDNA sequencing provides a simple but reliable approach to exclude NUMTs as source of misleading results.     

Adaptive evolution signals in mitochondrial genes of Europeans

Since modern Europeans appear to be descendants of the Late Pleistocene European peoples who survived the last glacial period, it is quite reasonable to expect the presence of adaptive genetic variants that originated in the Ice Age in the modern gene pool of Europeans. To find such adaptive variants, mitochondrial genomes have been analyzed of the modern population from Eastern and Central Europe belonging to haplogroups U4, U5, and V, that diversified during the Late Pleistocene and Holocene periods. Analysis of distribution of nonsynonymous and synonymous substitutions, as well as results of search for radical amino acid changes that arose under the influence of adaptation (positive destabilizing selection) allowed us to detect signals of molecular adaptation in different mitochondrial genes and haplogroups of mtDNA. However, there were very few strong adaptive signals (z > 3.09, P < 0.001) that could be due to the loss of adaptive mtDNA haplotypes during the Holocene warming.     

Metabolic Depression in Cunner (Tautogolabrus adspersus) Is Influenced by Ontogeny,and Enhances Thermal Tolerance

To examine the effect of ontogeny on metabolic depression in the cunner (Tautogolabrus adspersus), and to understand how ontogeny and the ability to metabolically depress influence this species'' upper thermal tolerance: 1) the metabolic rate of 9°C-acclimated cunner of three size classes [0.2–0.5 g, young of the year (YOY); 3–6 g, small; and 80–120 g, large (adult)] was measured during a 2°C per day decrease in temperature; and 2) the metabolic response of the same three size classes of cunner to an acute thermal challenge [2°C h⁻¹ from 10°C until Critical Thermal Maximum, CT_Max] was examined, and compared to that of the Atlantic cod (Gadus morhua). The onset-temperature for metabolic depression in cunner increased with body size, i.e. from 5°C in YOY cunner to 7°C in adults. In contrast, the extent of metabolic depression was ∼80% (Q₁₀ = ∼15) for YOY fish, ∼65% (Q₁₀ = ∼8) for small fish and ∼55% (Q₁₀ = ∼5) for adults, and this resulted in the metabolic scaling exponent (b) gradually increasing from 0.84 to 0.92 between 9°C to 1°C. All size classes of cunner had significantly (approximately 60%) lower routine metabolic rates at 10°C than Atlantic cod. However, there was no species'' difference in the temperature-induced maximum metabolic rate, and this resulted in factorial metabolic scope values that were more than two-fold greater for cunner, and CT_Max values that were 6–9°C higher (∼21 vs. 28°C). These results: 1) show that ontogeny influences the temperature of initiation and the extent of metabolic depression in cunner, but not O₂ consumption when in a hypometabolic state; and 2) suggest that the evolution of cold-induced metabolic depression in this northern wrasse species has not resulted in a trade-off with upper thermal tolerance, but instead, an enhancement of this species'' metabolic plasticity.     

The Genetic Legacy of the Pre-Colonial Period in Contemporary Bolivians

Only a few genetic studies have been carried out to date in Bolivia. However, some of the most important (pre)historical enclaves of South America were located in these territories. Thus, the (sub)-Andean region of Bolivia was part of the Inca Empire, the largest state in Pre-Columbian America. We have genotyped the first hypervariable region (HVS-I) of 720 samples representing the main regions in Bolivia, and these data have been analyzed in the context of other pan-American samples (>19,000 HVS-I mtDNAs). Entire mtDNA genome sequencing was also undertaken on selected Native American lineages. Additionally, a panel of 46 Ancestry Informative Markers (AIMs) was genotyped in a sub-set of samples. The vast majority of the Bolivian mtDNAs (98.4%) were found to belong to the main Native American haplogroups (A: 14.3%, B: 52.6%, C: 21.9%, D: 9.6%), with little indication of sub-Saharan and/or European lineages; however, marked patterns of haplogroup frequencies between main regions exist (e.g. haplogroup B: Andean [71%], Sub-Andean [61%], Llanos [32%]). Analysis of entire genomes unraveled the phylogenetic characteristics of three Native haplogroups: the pan-American haplogroup B2b (originated ∼21.4 thousand years ago [kya]), A2ah (∼5.2 kya), and B2o (∼2.6 kya). The data suggest that B2b could have arisen in North California (an origin even in the north most region of the American continent cannot be disregarded), moved southward following the Pacific coastline and crossed Meso-America. Then, it most likely spread into South America following two routes: the Pacific path towards Peru and Bolivia (arriving here at about ∼15.2 kya), and the Amazonian route of Venezuela and Brazil southwards. In contrast to the mtDNA, Ancestry Informative Markers (AIMs) reveal a higher (although geographically variable) European introgression in Bolivians (25%). Bolivia shows a decreasing autosomal molecular diversity pattern along the longitudinal axis, from the Altiplano to the lowlands. Both autosomes and mtDNA revealed a low impact (1–2%) of a sub-Saharan component in Bolivians.     

Uniparental Genetic Heritage of Belarusians: Encounter of Rare Middle Eastern Matrilineages with a Central European Mitochondrial DNA Pool

Ethnic Belarusians make up more than 80% of the nine and half million people inhabiting the Republic of Belarus. Belarusians together with Ukrainians and Russians represent the East Slavic linguistic group, largest both in numbers and territory, inhabiting East Europe alongside Baltic-, Finno-Permic- and Turkic-speaking people. Till date, only a limited number of low resolution genetic studies have been performed on this population. Therefore, with the phylogeographic analysis of 565 Y-chromosomes and 267 mitochondrial DNAs from six well covered geographic sub-regions of Belarus we strove to complement the existing genetic profile of eastern Europeans. Our results reveal that around 80% of the paternal Belarusian gene pool is composed of R1a, I2a and N1c Y-chromosome haplogroups – a profile which is very similar to the two other eastern European populations – Ukrainians and Russians. The maternal Belarusian gene pool encompasses a full range of West Eurasian haplogroups and agrees well with the genetic structure of central-east European populations. Our data attest that latitudinal gradients characterize the variation of the uniparentally transmitted gene pools of modern Belarusians. In particular, the Y-chromosome reflects movements of people in central-east Europe, starting probably as early as the beginning of the Holocene. Furthermore, the matrilineal legacy of Belarusians retains two rare mitochondrial DNA haplogroups, N1a3 and N3, whose phylogeographies were explored in detail after de novo sequencing of 20 and 13 complete mitogenomes, respectively, from all over Eurasia. Our phylogeographic analyses reveal that two mitochondrial DNA lineages, N3 and N1a3, both of Middle Eastern origin, might mark distinct events of matrilineal gene flow to Europe: during the mid-Holocene period and around the Pleistocene-Holocene transition, respectively.