The Neolithic transition from hunting and gathering to farming and cattle breeding marks one of the most drastic cultural changes in European prehistory. Short stretches of ancient mitochondrial DNA (mtDNA) from skeletons of pre-Neolithic hunter-gatherers as well as early Neolithic farmers support the demic diffusion model where a migration of early farmers from the Near East and a replacement of pre-Neolithic hunter-gatherers are largely responsible for cultural innovation and changes in subsistence strategies during the Neolithic revolution in Europe. In order to test if a signal of population expansion is still present in modern European mitochondrial DNA, we analyzed a comprehensive dataset of 1,151 complete mtDNAs from present-day Europeans. Relying upon ancient DNA data from previous investigations, we identified mtDNA haplogroups that are typical for early farmers and hunter-gatherers, namely H and U respectively. Bayesian skyline coalescence estimates were then used on subsets of complete mtDNAs from modern populations to look for signals of past population expansions. Our analyses revealed a population expansion between 15,000 and 10,000 years before present (YBP) in mtDNAs typical for hunters and gatherers, with a decline between 10,000 and 5,000 YBP. These corresponded to an analogous population increase approximately 9,000 YBP for mtDNAs typical of early farmers. The observed changes over time suggest that the spread of agriculture in Europe involved the expansion of farming populations into Europe followed by the eventual assimilation of resident hunter-gatherers. Our data show that contemporary mtDNA datasets can be used to study ancient population history if only limited ancient genetic data is available.
Citation: Fu Q, Rudan P, Pääbo S, Krause J (2012) Complete Mitochondrial Genomes Reveal Neolithic Expansion into Europe. PLoS ONE7(3): e32473. https://doi.org/10.1371/journal.pone.0032473
Editor: Carles Lalueza-Fox, Institut de Biologia Evolutiva - Universitat Pompeu Fabra, Spain
Received: November 3, 2011; Accepted: January 31, 2012; Published: March 13, 2012
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Funding: This research was funded by the Max Planck Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Archaeological evidence suggests that agrarian societies emerged in Western Asia around 11,000 years before present (YBP)  and rapidly spread reaching South Eastern Europe by approximately 9,000 YBP . The transition from pre-Neolithic hunter-gatherer societies to Neolithic farming and cattle breeding is often called the Neolithic revolution and marks one of the most pronounced cultural changes in European prehistory ,  that can be observed in the archaeological record all over Europe . By around 5,000 YBP almost all populations in mainland Europe practiced agriculture. There are two main hypotheses for how Neolithic cultures spread across Europe. The first, suggests cultural transmission as the main factor, i.e. that the new technologies and subsistence strategies were learned from neighbouring groups . The second hypothesis suggests an expansion of farmer populations from the Near East into Europe, replacing most of the pre-Neolithic hunter-gatherer populations. This population replacement model, termed demic diffusion, is conceived as population spread and expansion, with limited admixture with resident populations.
Recently, mitochondrial DNA (mtDNA) from skeletal remains of European early farmers and late hunter-gatherers has been retrieved –. The frequency of mtDNA haplogroups, defined by substitutions shared by related mtDNA types (Phylotree.org-mtDNA tree build 12), in early farmers across Europe , – was found to be overall similar to those in modern Europeans (Figure 1, Figure S4, Figure S5), while pre-Neolithic hunter-gatherers appear to be quite distinct (Figure 1). In particular, 83% (19 out of 23) of hunter-gatherers analyzed to date carry mtDNAs belonging to haplogroup U , ,  and none of the hunter-gatherers fall in haplogroup H. In contrast, haplogroup U has been found in only 13 of 105 (around 12%) individuals from early farming cultures of Europe and it occurs in less than 21% of modern Europeans, while haplogroup H comprises between 25% and 37% of mtDNAs retrieved from early farming cultures (Figure S4) and is in about 30% of contemporary Europeans (Figure 1). The mtDNA data thus suggest that the pre-Neolithic populations in Europe were largely replaced by in-coming Neolithic farming groups, with a maximum mtDNA contribution of around 20% from pre-Neolithic hunter-gatherers –. The genetic contribution of pre-Neolithic hunter-gatherers to later Neolithic populations is furthermore supported by a similar frequency of U subhaplogroups (U5, U4, K and U2) that were found in pre-Neolithic hunter-gatherers (Figure S3) and are still the most common U-subhaplogroups in modern Central Europeans (Figure S5).
The mtDNA sequences determined from early farmers and hunter-gatherers are however less than 400 bp in length and their number is quite small (105 and 21, respectively), limiting the information that can be gained about population sizes and putative population expansions in the past. Here, we use a total of 1,151 complete mtDNAs from present-day populations in Europe, along with 38 mtDNAs which we determined from a modern population in Croatia, to estimate the frequency of the haplogroup U, putatively typical of hunter-gatherers, and mtDNAs of the haplogroup H, putatively typical of the early farming cultures. We then use these data to study potential differences in signatures of demographic history of hunter-gatherers and farmers in Europe that are discernable in present-day European mtDNAs.
Results and Discussion
A total of 1,151 complete mtDNA sequences from present-day Europeans were collected from GenBank (dataset 1). Due to various ascertainment biases, such as selected sequencing of rare variants – in this data set, which might influence the analysis and conclusions drawn, we first used an unbiased randomly selected subset of 259 complete mtDNAs from all of Europe (dataset 2) . Secondly, to test for potential non-reported ascertainment biases in dataset 2, we furthermore generated 38 complete mtDNAs from random villagers from Croatia (dataset 3). In each data set, mtDNAs of the U-type and H-type were identified (Table 1, Table 2, Table 3).
Whereas H-type mtDNAs have on average six nucleotide differences in their coding region (position 577–16023) (Figure 2, green), U-type mtDNAs have on average 18 differences (Figure 2, red). The distribution of pair-wise differences among the H-type mtDNAs shows a clear mode around 6 differences whereas the U-types have a mode around 22 differences. Such peaks may be caused by past population expansions  (Figure S7, Figure S8, Figure S9). They would suggest that H-type mtDNAs experienced a recent population expansion while U-type mtDNAs experienced a much older population expansion. Notably, these differences in the distributions of pair-wise nucleotide differences are not caused by sequencing of a selected set of mtDNA types present in GenBank, since dataset 2 as well as the individuals sequenced from Croatia (dataset 3) show an average number of differences as well as modes very similar to dataset 1.
In order to analyze potential population size changes over time, we calculated Bayesian skyline plots using the BEAST package  for dataset 1 and dataset 2 (dataset 3 was too small). In both datasets, the direct comparison of skyline plots between the H-type and the U-type mtDNAs (Figure 3) reveals a population increase for individuals carrying the H-type starting around 9,000 YBP and continuing to the present, whereas the U-type shows a population expansion between 20,000 and 10,000 YBP with a putative period of slight decrease between 6,000 and 5,000 YBP (Figure S6A, B). For both U-type and H-type mtDNAs, we observe similar patterns of population growth starting around 4,000 YBP to the present (Figure 3). Thus, H-type and U-type mtDNAs show a distinct population history before 5,000 YBP, possibly reflecting that they were primarily present in different populations with different origins and histories.
The x-axis shows time in years before present, the y axis the effective population size Ne. The center line represents the mean of Ne estimate, upper and lower lines are the 95% posterior density intervals. We assumed a mutation rate of the coding regions of 1.691×10−8 substitutions per site and year –.
The high frequency of H-type mtDNAs in European Neolithic populations and its complete absence in pre-Neolithic hunter-gatherers suggests that H-type mtDNAs arrived with early farmers in Europe. The population size increase observed between 9,000 and 5,000 YBP likely represents the population expansion that accompanied the Neolithic revolution. In contrast, U-type mtDNAs show an increase in population size around 15,000 to 10,000 YBP, which coincides with the end of the last glacial maximum in Europe and a northwards expansion of hunter-gatherer populations. The data suggests that this population remained rather constant after 10,000 YBP until the onset of the Neolithic revolution. However, the H-type mtDNA population size seems to experience an exponential increase around 7,000 YBP, suggesting that both populations are not yet fused. After 4,000 YBP, no archaeological remains of hunter-gatherers were found in central Europe . From approximately that time on, both H- and U-type mtDNAs expand in a similar way. This may reflect fusion of the two populations where these mtDNAs were prevalent.
These results suggest that H-type mtDNAs in the European mtDNA gene pool show evidence of a population expansion related to the spread of animal husbandry and farming. In contrast, U-type mtDNAs seem to represent earlier hunter-gatherers that adopted farming practices and admixed with immigrant farming populations. In agreement with this scenario, the only non-agricultural population of Europe, the Saami in Northern Scandinavia and Russia, carry about 49% of U-type mtDNAs .
Materials and Methods
DNA Sequence Data
Due to the high mutation rate and the risk of homoplasy, we excluded non-coding regions from our analysis. We identified haplogroups for each mtDNA using the database phylotree (based on Phylotree.org-mtDNA build 12). For the whole European mtDNA dataset comprising 1,151 sequences we identified 332 mtDNAs falling into haplogroup H, representing farmers for our purposes, and 227 mtDNAs falling into haplogroup U, typical for early hunter-gatherers (Figure 1B). For the sampled 259 population-wide data, we identified 144 mtDNAs of type H and 41 of type U. Further, we enriched, sequenced and assembled mitochondrial genomes (Supporting Method S1) from a contemporary populations of villagers sampled in the Northeast and Northwest of Croatia (Figure S1, Figure S2, Table S1). In this Croatian dataset we identified 19 mtDNA sequences of type H and 6 of type U (Figure 1B).
Pairwise nucleotide distances were calculated using MEGA 4 . Skyline plots were estimated using coding regions (positions 577–16023) from the U- and the H- type mtDNA datasets using the Bayesian algorithm of BEAST v1.5.3 . The General Time Reversible sequence evolution model with a fixed fraction of invariable sites (GTR+I) was determined by the best-fit model approach of Modeltest and PAUP* . For each analysis, we used parallel models that assumes a Bayesian skyline coalescent and a constant size coalescent across the phylogeny and ran 50,000,000 generations of the Markov Chain Monte Carlo with the first 5,000,000 generations discarded as burn-in. Final model was chosen by using Bayes factors (BF>20 is strong support for the favored model –, and reported as log10 Bayes factors (log10 BF). Here the Bayesian skyline model fits the data better than constant population size in H-type (dataset 1: log10 = 2.69; dataset 2 log10 = 6.86). And the Bayesian skyline model cannot be rejected in U-type (dataset 1: log10 = 0.34; dataset 2 log10 = 0.91). The alignment was analyzed using a strict molecular clock with a substitution rate of 1.691×10−8 substitutions per site and year –.
Map of villages sampled in the Northeast and Northwest of Croatia.
Read coverage (logarithmic scale; upper part) and GC content (lower part) along the complete mitochondrial genome for the 50 Croatian samples. Coverage is not highly correlated with GC content.
Haplogroup frequency of pre-Neolithic samples.
Haplogroup frequency of Neolithic samples.
Haplogroup frequency of modern human sets.
Estimates for the effective population size (Ne) over time for haplotype U mtDNA sequences for the full (A) and the subsampled (B) European mtDNA datasets over 35,000 years. Estimated effective population size (Ne) over time of type H (red) and type U5 mtDNA haplotypes (blue) for the complete European mtDNA dataset (C) as well as for the sampled dataset (D). Estimates for the effective population size (Ne) for haplotype U5 mtDNA sequences for the full (E) and the sampled (F) European mtDNA datasets over 16,000 years. The x-axis shows time in years before present, the y axis the effective population size Ne. The center line represents the mean of Ne estimate, upper and lower lines are the 95% posterior density intervals. We assumed a mutation rate of the coding regions of 1.691×10−8 substitutions per site and year.
Phylogenetic tree of mtDNAs from dataset 1. The phylogeny was estimated with a Bayesian approach under a GTR+I+R model using 332 present-day European mtDNA sequences of haplogroup H and 228 sequences from haplogroup U. The outgroup is a African mtDNA sequence.
Phylogenetic tree of mtDNAs from dataset 2. The phylogeny was estimated with a Bayesian approach under a GTR+I+R model using 144 present-day European mtDNA sequences of haplogroup H and 41 sequences from haplogroup U. The outgroup is the African mtDNA sequence.
Phylogenetic tree of mtDNAs of dataset 3. The phylogeny was estimated with a Bayesian approach under a GTR+I+R model using 20 present-day Croatian mtDNA sequences of haplogroup H and 7 sequences from haplogroup U. The outgroup is the African mtDNA sequence.
Supporting sequence information of Croatians.
The authors thank: Ellen D. Gunnarsdottir for helping with the analysis; Janet Kelso, Martin Kircher, Anja Heinze and Kirsten Bos for comments on the manuscript; Marike Schreiber for polishing the figure.
Analyzed the data: QF. Contributed reagents/materials/analysis tools: PR. Wrote the paper: JK QM SP. Designed the experiment: QF PR JK. Conducted the lab work: QF JK.
- 1. Daniel Zohary MH (1993) Domestication of Plants in the Old World: The Origin and Spread of Cultivated Plants in West Asia, Europe, and the Nile Valley. Oxford: Clarendon Press. MH Daniel Zohary1993Domestication of Plants in the Old World: The Origin and Spread of Cultivated Plants in West Asia, Europe, and the Nile ValleyOxfordClarendon Press
- 2. Greenfield H (2006) The spatial organization of Early Neolithic settlements in temperate southeastern Europe: a view from Blagotin, Serbia. In: Robertson JDS ElizabethC, Fernandez DeepikaC, Zender MarcU, editors. In Space and Spatial Analysis in Archaeology. Calgary: University of Calgary Press. pp. 69–79.H. Greenfield2006The spatial organization of Early Neolithic settlements in temperate southeastern Europe: a view from Blagotin, Serbia.ElizabethC Robertson JDSDeepikaC FernandezMarcU ZenderIn Space and Spatial Analysis in ArchaeologyCalgaryUniversity of Calgary Press6979
- 3. Alasdair Whittle VC, editor. (2007) Going over: the mesolithic-neolithic transition in North-West Europe. Oxford: Oxford University Press. pp. 1–3.VC Alasdair Whittle2007Going over: the mesolithic-neolithic transition in North-West EuropeOxfordOxford University Press13
- 4. Zvelebil M (1989) On the transition to farming in Europe, or what was spreading with the Neolithic: a relay to Ammerman. Antiqutiy 63: 379–383.M. Zvelebil1989On the transition to farming in Europe, or what was spreading with the Neolithic: a relay to Ammerman.Antiqutiy63379383
- 5. Harris DR, editor. (1996) The Origins and Spread of Agriculture and Pastoralism in Eurasia. London: University College of London Press. pp. 552–574.DR Harris1996The Origins and Spread of Agriculture and Pastoralism in EurasiaLondonUniversity College of London Press552574
- 6. Alena Lukes MZ, editor. (2004) LBK Dialogues: Studies in the Formation of the Linear Pottery Culture. Oxford: British Archaeological Reports. pp. 183–205.MZ Alena Lukes2004LBK Dialogues: Studies in the Formation of the Linear Pottery CultureOxfordBritish Archaeological Reports183205
- 7. Sampietro ML, Lao O, Caramelli D, Lari M, Pou R, et al. (2007) Palaeogenetic evidence supports a dual model of Neolithic spreading into Europe. Proceedings of the Royal Society B-Biological Sciences 274: 2161–2167.ML SampietroO. LaoD. CaramelliM. LariR. Pou2007Palaeogenetic evidence supports a dual model of Neolithic spreading into Europe.Proceedings of the Royal Society B-Biological Sciences27421612167
- 8. Haak W, Forster P, Bramanti B, Matsumura S, Brandt G, et al. (2005) Ancient DNA from the first European farmers in 7500-year-old Neolithic sites. Science 310: 1016–1018.W. HaakP. ForsterB. BramantiS. MatsumuraG. Brandt2005Ancient DNA from the first European farmers in 7500-year-old Neolithic sites.Science31010161018
- 9. Bramanti B, Thomas MG, Haak W, Unterlaender M, Jores P, et al. (2009) Genetic Discontinuity Between Local Hunter-Gatherers and Central Europe's First Farmers. Science 326: 137–140.B. BramantiMG ThomasW. HaakM. UnterlaenderP. Jores2009Genetic Discontinuity Between Local Hunter-Gatherers and Central Europe's First Farmers.Science326137140
- 10. Haak W, Balanovsky O, Sanchez JJ, Koshel S, Zaporozhchenko V, et al. (2010) Ancient DNA from European early neolithic farmers reveals their near eastern affinities. PLoS Biol 8: e1000536.W. HaakO. BalanovskyJJ SanchezS. KoshelV. Zaporozhchenko2010Ancient DNA from European early neolithic farmers reveals their near eastern affinities.PLoS Biol8e1000536
- 11. Deguilloux MF, Soler L, Pemonge MH, Scarre C, Joussaume R, et al. (2011) News From the West: Ancient DNA From a French Megalithic Burial Chamber. American Journal of Physical Anthropology 144: 108–118.MF DeguillouxL. SolerMH PemongeC. ScarreR. Joussaume2011News From the West: Ancient DNA From a French Megalithic Burial Chamber.American Journal of Physical Anthropology144108118
- 12. Lacan M, Keyser C, Ricaut FX, Brucato N, Duranthon F, et al. (2011) Ancient DNA reveals male diffusion through the Neolithic Mediterranean route. Proceedings of the National Academy of Sciences of the United States of America 108: 9788–9791.M. LacanC. KeyserFX RicautN. BrucatoF. Duranthon2011Ancient DNA reveals male diffusion through the Neolithic Mediterranean route.Proceedings of the National Academy of Sciences of the United States of America10897889791
- 13. Gamba C, Fernandez E, Tirado M, Deguilloux MF, Pemonge MH, et al. (2012) Ancient DNA from an Early Neolithic Iberian population supports a pioneer colonization by first farmers. Mol Ecol 21: 45–56.C. GambaE. FernandezM. TiradoMF DeguillouxMH Pemonge2012Ancient DNA from an Early Neolithic Iberian population supports a pioneer colonization by first farmers.Mol Ecol214556
- 14. Krause J, Briggs AW, Kircher M, Maricic T, Zwyns N, et al. (2010) A complete mtDNA genome of an early modern human from Kostenki, Russia. Curr Biol 20: 231–236.J. KrauseAW BriggsM. KircherT. MaricicN. Zwyns2010A complete mtDNA genome of an early modern human from Kostenki, Russia.Curr Biol20231236
- 15. Pala M, Achilli A, Olivieri A, Kashani BH, Perego UA, et al. (2009) Mitochondrial haplogroup U5b3: a distant echo of the epipaleolithic in Italy and the legacy of the early Sardinians. American Journal of Human Genetics 84: 814–821.M. PalaA. AchilliA. OlivieriBH KashaniUA Perego2009Mitochondrial haplogroup U5b3: a distant echo of the epipaleolithic in Italy and the legacy of the early Sardinians.American Journal of Human Genetics84814821
- 16. Pereira L, Goncalves J, Franco-Duarte R, Silva J, Rocha T, et al. (2007) No evidence for an mtDNA role in sperm motility: Data from complete sequencing of asthenozoospermic males. Molecular Biology and Evolution 24: 868–874.L. PereiraJ. GoncalvesR. Franco-DuarteJ. SilvaT. Rocha2007No evidence for an mtDNA role in sperm motility: Data from complete sequencing of asthenozoospermic males.Molecular Biology and Evolution24868874
- 17. Carelli V, Achilli A, Valentino ML, Rengo C, Semino O, et al. (2006) Haplogroup effects and recombination of mitochondrial DNA: Novel clues from the analysis of Leber hereditary optic neuropathy pedigrees. American Journal of Human Genetics 78: 564–574.V. CarelliA. AchilliML ValentinoC. RengoO. Semino2006Haplogroup effects and recombination of mitochondrial DNA: Novel clues from the analysis of Leber hereditary optic neuropathy pedigrees.American Journal of Human Genetics78564574
- 18. Malyarchuk B, Grzybowski T, Derenko M, Perkova M, Vanecek T, et al. (2008) Mitochondrial DNA Phylogeny in Eastern and Western Slavs. Molecular Biology and Evolution 25: 1651–1658.B. MalyarchukT. GrzybowskiM. DerenkoM. PerkovaT. Vanecek2008Mitochondrial DNA Phylogeny in Eastern and Western Slavs.Molecular Biology and Evolution2516511658
- 19. Herrnstadt C, Elson JL, Fahy E, Preston G, Turnbull DM, et al. (2002) Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups. American Journal of Human Genetics 70: 1152–1171.C. HerrnstadtJL ElsonE. FahyG. PrestonDM Turnbull2002Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.American Journal of Human Genetics7011521171
- 20. Rogers AR, Harpending H (1992) Population growth makes waves in the distribution of pairwise genetic differences. Molecular Biology and Evolution 9: 552–569.AR RogersH. Harpending1992Population growth makes waves in the distribution of pairwise genetic differences.Molecular Biology and Evolution9552569
- 21. Atkinson QD, Gray RD, Drummond AJ (2008) mtDNA Variation Predicts Population Size in Humans and Reveals a Major Southern Asian Chapter in Human Prehistory. Molecular Biology and Evolution 25: 468–474.QD AtkinsonRD GrayAJ Drummond2008mtDNA Variation Predicts Population Size in Humans and Reveals a Major Southern Asian Chapter in Human Prehistory.Molecular Biology and Evolution25468474
- 22. Nowark M (2007) Middle and Late Holocene hunter-gatherers in East Central Europe: changing paradigms of the ‘non-Neolithic’ way of life. Ljubljana, SLOVENIE: Univerza v Ljubljani, Filozofska fakulteta, Oddelek za Arhaelogijo. 15 p.M. Nowark2007Middle and Late Holocene hunter-gatherers in East Central Europe: changing paradigms of the ‘non-Neolithic’ way of lifeLjubljana, SLOVENIEUniverza v Ljubljani, Filozofska fakulteta, Oddelek za Arhaelogijo15
- 23. Tambets K, Rootsi S, Kivisild T, Help H, Serk P, et al. (2004) The Western and Eastern Roots of the Saami–the Story of Genetic “Outliers” Told by Mitochondrial DNA and Y Chromosomes. The American Journal of Human Genetics 74: 661–682.K. TambetsS. RootsiT. KivisildH. HelpP. Serk2004The Western and Eastern Roots of the Saami–the Story of Genetic “Outliers” Told by Mitochondrial DNA and Y Chromosomes.The American Journal of Human Genetics74661682
- 24. Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Molecular Biology and Evolution 24: 1596–1599.K. TamuraJ. DudleyM. NeiS. Kumar2007MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0.Molecular Biology and Evolution2415961599
- 25. Drummond A, Rambaut A (2007) BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evolutionary Biology 7: 214.A. DrummondA. Rambaut2007BEAST: Bayesian evolutionary analysis by sampling trees.BMC Evolutionary Biology7214
- 26. Posada D, Crandall KA (1998) MODELTEST: testing the model of DNA substitution. Bioinformatics 14: 817–818.D. PosadaKA Crandall1998MODELTEST: testing the model of DNA substitution.Bioinformatics14817818
- 27. Newton MA, Raftery AE, Davison AC, Bacha M, Celeux G, et al. (1994) Approximate Bayesian-Inference with the Weighted Likelihood Bootstrap. Journal of the Royal Statistical Society Series B-Methodological 56: 3–48.MA NewtonAE RafteryAC DavisonM. BachaG. Celeux1994Approximate Bayesian-Inference with the Weighted Likelihood Bootstrap.Journal of the Royal Statistical Society Series B-Methodological56348
- 28. Drummond AJ, Rambaut A (2007) BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7: 214.AJ DrummondA. Rambaut2007BEAST: Bayesian evolutionary analysis by sampling trees.BMC Evol Biol7214
- 29. Suchard MA, Weiss RE, Sinsheimer JS (2001) Bayesian selection of continuous-time Markov chain evolutionary models. Molecular Biology and Evolution 18: 1001–1013.MA SuchardRE WeissJS Sinsheimer2001Bayesian selection of continuous-time Markov chain evolutionary models.Molecular Biology and Evolution1810011013
- 30. Ho SY, Phillips MJ, Cooper A, Drummond AJ (2005) Time dependency of molecular rate estimates and systematic overestimation of recent divergence times. Molecular Biology and Evolution 22: 1561–1568.SY HoMJ PhillipsA. CooperAJ Drummond2005Time dependency of molecular rate estimates and systematic overestimation of recent divergence times.Molecular Biology and Evolution2215611568
- 31. Friedlaender J, Schurr T, Gentz F, Koki G, Friedlaender F, et al. (2005) Expanding Southwest Pacific mitochondrial haplogroups P and Q. Molecular Biology and Evolution 22: 1506–1517.J. FriedlaenderT. SchurrF. GentzG. KokiF. Friedlaender2005Expanding Southwest Pacific mitochondrial haplogroups P and Q.Molecular Biology and Evolution2215061517
- 32. Schonberg A, Theunert C, Li M, Stoneking M, Nasidze I (2011) High-throughput sequencing of complete human mtDNA genomes from the Caucasus and West Asia: high diversity and demographic inferences. Eur J Hum Genet. A. SchonbergC. TheunertM. LiM. StonekingI. Nasidze2011High-throughput sequencing of complete human mtDNA genomes from the Caucasus and West Asia: high diversity and demographic inferences.Eur J Hum Genet
- 33. Finnilä S, Lehtonen MS, Majamaa K (2001) Phylogenetic Network for European mtDNA. The American Journal of Human Genetics 68: 1475–1484.S. FinniläMS LehtonenK. Majamaa2001Phylogenetic Network for European mtDNA.The American Journal of Human Genetics6814751484
- 34. Pello R, Martin MA, Carelli V, Nijtmans LG, Achilli A, et al. (2008) Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease. Hum Mol Genet 17: 4001–4011.R. PelloMA MartinV. CarelliLG NijtmansA. Achilli2008Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease.Hum Mol Genet1740014011
- 35. Gasparre G, Porcelli AM, Bonora E, Pennisi LF, Toller M, et al. (2007) Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors. Proc Natl Acad Sci U S A 104: 9001–9006.G. GasparreAM PorcelliE. BonoraLF PennisiM. Toller2007Disruptive mitochondrial DNA mutations in complex I subunits are markers of oncocytic phenotype in thyroid tumors.Proc Natl Acad Sci U S A10490019006
- 36. Fraumene C, Belle EMS, Castrì L, Sanna S, Mancosu G, et al. (2006) High Resolution Analysis and Phylogenetic Network Construction Using Complete mtDNA Sequences in Sardinian Genetic Isolates. Molecular Biology and Evolution 23: 2101–2111.C. FraumeneEMS BelleL. CastrìS. SannaG. Mancosu2006High Resolution Analysis and Phylogenetic Network Construction Using Complete mtDNA Sequences in Sardinian Genetic Isolates.Molecular Biology and Evolution2321012111
- 37. Achilli A, Rengo C, Magri C, Battaglia V, Olivieri A, et al. (2004) The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool. American Journal of Human Genetics 75: 910–918.A. AchilliC. RengoC. MagriV. BattagliaA. Olivieri2004The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool.American Journal of Human Genetics75910918
- 38. Behar DM, Metspalu E, Kivisild T, Rosset S, Tzur S, et al. (2008) Counting the founders: the matrilineal genetic ancestry of the Jewish Diaspora. PLoS One 3: e2062.DM BeharE. MetspaluT. KivisildS. RossetS. Tzur2008Counting the founders: the matrilineal genetic ancestry of the Jewish Diaspora.PLoS One3e2062
- 39. Ennafaa H, Cabrera VM, Abu-Amero KK, Gonzalez AM, Amor MB, et al. (2009) Mitochondrial DNA haplogroup H structure in North Africa. BMC Genet 10: 8.H. EnnafaaVM CabreraKK Abu-AmeroAM GonzalezMB Amor2009Mitochondrial DNA haplogroup H structure in North Africa.BMC Genet108
- 40. Maca-Meyer N, Gonzalez AM, Larruga JM, Flores C, Cabrera VM (2001) Major genomic mitochondrial lineages delineate early human expansions. BMC Genet 2: 13.N. Maca-MeyerAM GonzalezJM LarrugaC. FloresVM Cabrera2001Major genomic mitochondrial lineages delineate early human expansions.BMC Genet213
- 41. Álvarez-Iglesias V, Mosquera-Miguel A, Cerezo M, Quintáns B, Zarrabeitia MT, et al. (2009) New Population and Phylogenetic Features of the Internal Variation within Mitochondrial DNA Macro-Haplogroup R0. PLoS One 4: e5112.V. Álvarez-IglesiasA. Mosquera-MiguelM. CerezoB. QuintánsMT Zarrabeitia2009New Population and Phylogenetic Features of the Internal Variation within Mitochondrial DNA Macro-Haplogroup R0.PLoS One4e5112
- 42. Maasz A, Komlosi K, Hadzsiev K, Szabo Z, Willems PJ, et al. (2008) Phenotypic variants of the deafness-associated mitochondrial DNA A7445G mutation. Curr Med Chem 15: 1257–1262.A. MaaszK. KomlosiK. HadzsievZ. SzaboPJ Willems2008Phenotypic variants of the deafness-associated mitochondrial DNA A7445G mutation.Curr Med Chem1512571262
- 43. Brisighelli F, Capelli C, Alvarez-Iglesias V, Onofri V, Paoli G, et al. (2009) The Etruscan timeline: a recent Anatolian connection. Eur J Hum Genet 17: 693–696.F. BrisighelliC. CapelliV. Alvarez-IglesiasV. OnofriG. Paoli2009The Etruscan timeline: a recent Anatolian connection.Eur J Hum Genet17693696
- 44. Achilli A, Rengo C, Battaglia V, Pala M, Olivieri A, et al. (2005) Saami and Berbers An Unexpected Mitochondrial DNA Link. American Journal of Human Genetics 76: 883–886.A. AchilliC. RengoV. BattagliaM. PalaA. Olivieri2005Saami and Berbers An Unexpected Mitochondrial DNA Link.American Journal of Human Genetics76883886