mtDNA Haplogroups and Frequency Patterns in Europe
2000; Elsevier BV; Volume: 66; Issue: 3 Linguagem: Inglês
10.1086/302789
ISSN1537-6605
AutoresAntonio Torroni, Martin Richards, Vincent Macaulay, Peter Forster, Richard Villems, Søren Nørby, Marja‐Liisa Savontaus, Kirsi Huoponen, Rosaria Scozzari, Hans‐Jürgen Bandelt,
Tópico(s)Genomics and Phylogenetic Studies
ResumoTo the Editor: Recently, an article by Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar), who used (i) SAAP analysis to analyze the population frequencies of mtDNA haplogroups and (ii) AIDA analysis to examine both the frequency and the sequence similarity of truncated mtDNA sequences, appeared in this Journal. The main outcome of their study was that “the overall patterns of mtDNA diversity appear to be poorly significant in Europe.” The raw data comprised 2,619 hypervariable segment I (HVS-I) sequences (denoted as “HVR-I” [hypervariable region I] sequences by Simoni et al. [2000]) that were obtained from 36 regions or populations of Europe, the Near East, and the Caucasus and that were collected from both the literature and unpublished sources. Simoni et al. ostensibly grouped the HVS-I sequences according to haplogroup motifs proposed elsewhere (Richards et al. Richards et al., 1998Richards MB Macaulay VA Bandelt H-J Sykes BC Phylogeography of mitochondrial DNA in western Europe.Ann Hum Genet. 1998; 62: 241-260Crossref PubMed Google Scholar), and they reported the resulting frequencies for each region/population in table 3 in their study. We have checked the input data displayed in table 3 and have found serious technical errors affecting numerous entries. More critically, the mtDNA categories that they report correspond neither to their own criteria nor to the haplogroup definitions established in the literature (to which they refer). Furthermore, their decision to truncate HVS-I information (and to disregard RFLP information) renders these data inadequate to differentiate even African and East Asian sequences from European sequences in many cases. Inspection of table 3 in the study by Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) reveals that (i) the data in the “Galicia” and “Spain: Central” rows have been, in part, crossed-over, (ii) the data in the “Belgium,” “Alps,” and “Turkey” rows have been computed with the use of sample sizes smaller than those reported in table 1 in the same study, (iii) the haplogroup “J” column has been totally randomized, and (iv) the “Other” column is complementary to the last four “superhaplogroup” columns but not to the first 11 haplogroup columns. As for item (iii), almost all positive entries in the haplogroup “J” column have been either displaced or calculated with the use of sample sizes corresponding to nearby rows. Hence, most entries in this column diverge widely from the real haplogroup J frequencies (see the last column of table 1 in the present study).Table 1Haplogroup J Frequencies According to Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar), a Crude Default Criterion, and Inference in the Present StudyHaplogroup J Frequency (%) According toPopulation/RegionaPopulation samples from published data tables and data banks cited by Simoni et al. (2000).Sample SizebSamples sizes are taken from the original sources, except for the Swiss sample, where four close maternal relatives were excluded (Richards et al. 1998, p 243). The sample sizes actually employed by Simoni et al. (2000) are given in parentheses whenever there is a discrepancy.Simoni et al. (2000)Crude Default Criterion (16126C–16294C)cThe mechanical application of this criterion captures a number of non-J sequences with motif 16126C–16362C, especially in Near Eastern populations.Inference in the Present StudydThe inference was made on the basis of (i) the motif 16069T–16126C and in conjunction with partial screening of 16069 (Richards et al. 1996), (ii) incorporating of HVS-II (J motif 00295T; Torroni et al. 1996) and RFLP information whenever available, and (iii) appreciating recurrent mutations at 16126.Austria117.012.811.1Cornwall69.021.721.7United Kingdom mainland1001.112.012.0Wales92.015.215.2Bulgaria306.710.010.0Adygei50.04.04.0Denmark33 (32).018.218.2Estonia28.07.17.1Finland794.48.98.9North Germany107 (108)17.89.38.4South Germany249.010.08.8Iceland531.417.017.0Druze45.011.16.7Tuscany49.018.414.3Karelia83.06.03.6Near East42.035.719.0Norway301.9.0.0Portugal54.07.45.6SaamieAccording to the original sources, an unspecified number of the 312 Saami may be related to each other.312 (240)1.93.8.0Basques106.02.82.8Catalunya15.06.76.7Mixed SpainfDenoted as “Central Spain” by Simoni et al. (2000).74.49.58.1Galicia92.09.88.7Sweden322.79.49.4Switzerland70 (72).011.411.4Turkey96 (95).016.715.6Volga-Finnic343.217.617.6a Population samples from published data tables and data banks cited by Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar).b Samples sizes are taken from the original sources, except for the Swiss sample, where four close maternal relatives were excluded (Richards et al. Richards et al., 1998Richards MB Macaulay VA Bandelt H-J Sykes BC Phylogeography of mitochondrial DNA in western Europe.Ann Hum Genet. 1998; 62: 241-260Crossref PubMed Google Scholar, p 243). The sample sizes actually employed by Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) are given in parentheses whenever there is a discrepancy.c The mechanical application of this criterion captures a number of non-J sequences with motif 16126C–16362C, especially in Near Eastern populations.d The inference was made on the basis of (i) the motif 16069T–16126C and in conjunction with partial screening of 16069 (Richards et al. Richards et al., 1996Richards M Côrte-Real H Forster P Macaulay V Wilkinson-Herbots H Demaine A Papiha S et al.Paleolithic and neolithic lineages in the European mitochondrial gene pool.Am J Hum Genet. 1996; 59: 185-203PubMed Google Scholar), (ii) incorporating of HVS-II (J motif 00295T; Torroni et al. Torroni et al., 1996Torroni A Huoponen K Francalacci P Petrozzi M Morelli L Scozzari R Obinu D et al.Classification of European mtDNAs from an analysis of three European populations.Genetics. 1996; 144: 1835-1850PubMed Google Scholar) and RFLP information whenever available, and (iii) appreciating recurrent mutations at 16126.e According to the original sources, an unspecified number of the 312 Saami may be related to each other.f Denoted as “Central Spain” by Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar). Open table in a new tab As an example of their haplogroup assignment, Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) specifically referred to the motif 16069T–16126C for haplogroup J, but they overlooked the fact that this criterion cannot formally be applied to the sequences in the study by Richards et al. (1996), since these were reported only between 16090 and 16365. This might explain some of the many “0” entries in the haplogroup “J” column of table 3 in the Simoni et al. study (see table 1 in the present study). Simoni et al. should have either adopted the haplogroup J frequencies reported by Richards et al. (Richards et al., 1996Richards M Côrte-Real H Forster P Macaulay V Wilkinson-Herbots H Demaine A Papiha S et al.Paleolithic and neolithic lineages in the European mitochondrial gene pool.Am J Hum Genet. 1996; 59: 185-203PubMed Google Scholar), excluded these population samples from their study, or trimmed all data to the shortest common segment. In the latter case, by employing the motif 16126C–16294C, one could take the default cluster JT-T (comprising all JT sequences that are not T) as a crude default criterion for haplogroup J (see table 1 in the present study). The discrepancies in haplogroup frequencies are by no means restricted to haplogroup J. Table 2 in the present study shows the marked contrast between published haplogroup frequencies and those assumed by Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) for the well-characterized Tuscan, Druze, and Adygei samples (which were typed for RFLPs as well as for HVS-I sequences by Torroni et al. [Torroni et al., 1996Torroni A Huoponen K Francalacci P Petrozzi M Morelli L Scozzari R Obinu D et al.Classification of European mtDNAs from an analysis of three European populations.Genetics. 1996; 144: 1835-1850PubMed Google Scholar] and Macaulay et al. [Macaulay et al., 1999Macaulay V Richards M Hickey E Vega E Cruciani F Guida V Scozzari R et al.The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs.Am J Hum Genet. 1999; 64: 232-249Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar]). The large differences in frequency for haplogroup H, the most-common European haplogroup, are due to the premise of Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) that haplogroup “H contains all sequences . . . that show none of the 22 substitutions considered in this study.” This extreme simplification results, on the one hand, in the dumping of large numbers of haplogroup H mtDNAs mainly into the default category “Other” and, on the other hand, in the inclusion of several non-H sequences within their haplogroup H category. For instance, by their criterion, 10/20 haplogroup H mtDNAs from the Tuscan sample (Torroni et al. Torroni et al., 1996Torroni A Huoponen K Francalacci P Petrozzi M Morelli L Scozzari R Obinu D et al.Classification of European mtDNAs from an analysis of three European populations.Genetics. 1996; 144: 1835-1850PubMed Google Scholar) would no longer be scored as “H,” whereas the U sequence 16051G–16309G–16318C would be scored as “H.” In consequence, the haplogroup H category described by Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) is bound to be highly polyphyletic in the mtDNA genealogy and does not reflect the spatial patterns of haplogroup H.Table 2Haplogroup Frequencies, According to Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) vs. the Original Studies, in Tuscan, Druze, and Adygei PopulationsHaplogroup Frequency (%)Population and StudySample SizeHIJKTU3U4U5VWXUaSimoni et al. (2000) had labeled this category as “KU,” which is a misnomer since U encompasses not only U3–U5 but also K and other clusters (Richards et al. 1998; Macaulay et al. 1999).Tuscan: Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar)4922.44.106.16.104.16.102.04.116.3 Francalacci et al. (Francalacci et al., 1996Francalacci P Bertranpetit J Calafell F Underhill PA Sequence diversity of the control region of mitochondrial DNA in Tuscany and its implications for the peopling of Europe.Am J Phys Anthropol. 1996; 100: 443-460Crossref PubMed Scopus (94) Google Scholar), Torroni et al. (Torroni et al., 1996Torroni A Huoponen K Francalacci P Petrozzi M Morelli L Scozzari R Obinu D et al.Classification of European mtDNAs from an analysis of three European populations.Genetics. 1996; 144: 1835-1850PubMed Google Scholar)bOf the 49 Tuscans reported in Francalacci et al. (1996), 48 were RFLP analyzed by Torroni et al. (1996).4841.74.214.66.310.402.14.202.18.316.7Adygei: Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar)5022.06.002.014.014.04.08.000028.0 Macaulay et al. (Macaulay et al., 1999Macaulay V Richards M Hickey E Vega E Cruciani F Guida V Scozzari R et al.The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs.Am J Hum Genet. 1999; 64: 232-249Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar)5030.004.02.014.014.02.08.002.0034.0Druze: Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar)4524.44.4015.64.40000017.815.6 Macaulay et al. (Macaulay et al., 1999Macaulay V Richards M Hickey E Vega E Cruciani F Guida V Scozzari R et al.The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs.Am J Hum Genet. 1999; 64: 232-249Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar)4513.32.26.715.64.40000026.726.7a Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) had labeled this category as “KU,” which is a misnomer since U encompasses not only U3–U5 but also K and other clusters (Richards et al. Richards et al., 1998Richards MB Macaulay VA Bandelt H-J Sykes BC Phylogeography of mitochondrial DNA in western Europe.Ann Hum Genet. 1998; 62: 241-260Crossref PubMed Google Scholar; Macaulay et al. Macaulay et al., 1999Macaulay V Richards M Hickey E Vega E Cruciani F Guida V Scozzari R et al.The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs.Am J Hum Genet. 1999; 64: 232-249Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar).b Of the 49 Tuscans reported in Francalacci et al. (Francalacci et al., 1996Francalacci P Bertranpetit J Calafell F Underhill PA Sequence diversity of the control region of mitochondrial DNA in Tuscany and its implications for the peopling of Europe.Am J Phys Anthropol. 1996; 100: 443-460Crossref PubMed Scopus (94) Google Scholar), 48 were RFLP analyzed by Torroni et al. (Torroni et al., 1996Torroni A Huoponen K Francalacci P Petrozzi M Morelli L Scozzari R Obinu D et al.Classification of European mtDNAs from an analysis of three European populations.Genetics. 1996; 144: 1835-1850PubMed Google Scholar). Open table in a new tab At this point, it is important to clarify what haplogroup classification entails. An mtDNA haplogroup, when properly defined, is a monophyletic clade of the mtDNA genealogy. Originally, high-resolution RFLP analysis (employing 14 enzymes) had been used for identification of clades by signature sites (Torroni et al. Torroni et al., 1992Torroni A Schurr TG Yang C-C Szathmary EJE Williams RC Schanfield MS Troup GA et al.Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations.Genetics. 1992; 130: 153-162PubMed Google Scholar, Torroni et al., 1993Torroni A Schurr TG Cabell MF Brown MD Neel JV Larsen M Smith DG et al.Asian affinities and continental radiation of the four founding Native American mtDNAs.Am J Hum Genet. 1993; 53: 563-590PubMed Google Scholar, Torroni et al., 1994aTorroni A Lott MT Cabell MF Chen YS Lavergne L Wallace DC mtDNA and the origin of Caucasians: identification of ancient Caucasian-specific haplogroups, one of which is prone to a recurrent somatic duplication in the D-loop region.Am J Hum Genet. 1994; 55: 760-776PubMed Google Scholar,Torroni et al., 1994bTorroni A Miller JA Moore LG Zamudio S Zhuang J Droma T Wallace DC Mitochondrial DNA analysis in Tibetmplications for the origin of the Tibetan population and its adaptation to high altitude.Am J Phys Anthropol. 1994; 93: 189-199Crossref PubMed Scopus (153) Google Scholar,Torroni et al., 1996Torroni A Huoponen K Francalacci P Petrozzi M Morelli L Scozzari R Obinu D et al.Classification of European mtDNAs from an analysis of three European populations.Genetics. 1996; 144: 1835-1850PubMed Google Scholar; Chen et al. 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Torroni et al., 1997Torroni A Petrozzi M D'Urbano L Sellitto D Zeviani M Carrara F Carducci C et al.Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484.Am J Hum Genet. 1997; 60: 1107-1121PubMed Google Scholar; Brown et al. Brown et al., 1998Brown MD Hosseini SH Torroni A Bandelt H-J Allen JC Schurr TG Scozzari R et al.mtDNA haplogroup X: an ancient link between Europe/Western Asia and North America?.Am J Hum Genet. 1998; 63: 1852-1861Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar; Starikovskaya et al. 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HVS-I data in combination with partial RFLPs can sometimes serve as a satisfactory substitute for a full RFLP analysis (Rando et al Rando et al., 1998Rando JC Pinto F Gonzáles AM Hernández M Larruga JM Cabrera VM Bandelt H-J Mitochondrial DNA analysis of northwest African populations reveals genetic exchanges with European, near-eastern, and sub-Saharan populations.Ann Hum Genet. 1998; 62: 531-550Crossref PubMed Google Scholar, Rando et al., 2000Rando JC Cabrera VM Larruga JM Hernández M Gonzáles AM Pinto F Bandelt H-J Phylogeographic patterns of mtDNA reflecting the colonisation of the Canary Islands.Ann Hum Genet. 2000; 63: 413-428Crossref Google Scholar; Kivisild et al. 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(Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar), yields even poorer results. For example, the motif 16223T–16278T, which was used by Simoni et al. to identify haplogroup X, would transfer most African L1/L2 sequences (Watson et al. Watson et al., 1997Watson E Forster P Richards M Bandelt H-J Mitochondrial footprints of human expansions in Africa.Am J Hum Genet. 1997; 61: 691-704Abstract Full Text PDF PubMed Scopus (289) Google Scholar; Rando et al. Rando et al., 1998Rando JC Pinto F Gonzáles AM Hernández M Larruga JM Cabrera VM Bandelt H-J Mitochondrial DNA analysis of northwest African populations reveals genetic exchanges with European, near-eastern, and sub-Saharan populations.Ann Hum Genet. 1998; 62: 531-550Crossref PubMed Google Scholar) into the then artefactual category “X.” For Europe, this is relevant insofar as a few L1/L2 sequences are present in Iberia (Rocha et al. Rocha et al., 1999Rocha H Flores C Campos Y Arenas J Vilarinho L Santorelli FM Torroni A About the “pathological” role of the mtDNA T3308C mutation….Am J Hum Genet. 1999; 65: 1457-1459Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar), and there even resides an African L1c sequence with the motif 16223T–16278T in the British data (Piercy et al. Piercy et al., 1993Piercy R Sullivan KM Benson N Gill P The application of mitochondrial DNA typing to the study of white Caucasian genetic identification.Int J Leg Med. 1993; 106: 85-90Crossref PubMed Scopus (213) Google Scholar). In addition, as was previously pointed out (Torroni et al. Torroni et al., 1996Torroni A Huoponen K Francalacci P Petrozzi M Morelli L Scozzari R Obinu D et al.Classification of European mtDNAs from an analysis of three European populations.Genetics. 1996; 144: 1835-1850PubMed Google Scholar; Macaulay et al. Macaulay et al., 1999Macaulay V Richards M Hickey E Vega E Cruciani F Guida V Scozzari R et al.The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs.Am J Hum Genet. 1999; 64: 232-249Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar), one has to be prepared for recurrent mutations in the HVS-I motifs (compare also figs. 4, 5, 8, and 9 of the study by Richards et al. [Richards et al., 1998Richards MB Macaulay VA Bandelt H-J Sykes BC Phylogeography of mitochondrial DNA in western Europe.Ann Hum Genet. 1998; 62: 241-260Crossref PubMed Google Scholar]). For instance, the frequency discrepancy (17.8% vs. 26.7%) for haplogroup X in the Druze sample (see table 2 in the present study) is due to the fact that Simoni et al. did not include four haplogroup X mtDNAs that have mutated to 16223C. Another of the many possible examples of misclassification caused by the use of truncated motifs is illustrated by 16129A–16223T, the motif used by Simoni et al. for classification of haplogroup I mtDNAs. Use of this truncated motif has led them to classify both the Asian haplogroup C mtDNAs (16129A–16223T–16298C–16327T) of the Adygei (6.0%) and the East African haplogroup M1 mtDNA (16129A–16189C–16223T–16249C–16311C–16359C) of the Druze (2.2%) as members of haplogroup I (see table 2 in the present study). The issue of haplogroups only affects the SAAP analysis. However, there are also serious difficulties with the AIDA analysis. Ideally, AIDA should be applied to full DNA-sequence data, but Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) included only 22/241 variant positions. One cannot expect that such a truncated data set would show much evidence of geographic patterns within Europe. Most of the haplogroup diagnostic variants in western Eurasian mtDNA are very ancient, and they probably evolved in the Near East and subsequently spread to Europe (Torroni et al. Torroni et al., 1998Torroni A Bandelt H-J D'Urbano L Lahermo P Moral P Sellitto D Rengo C et al.mtDNA analysis reveals a major late Paleolithic population expansion from southwestern to northeastern Europe.Am J Hum Genet. 1998; 62: 1137-1152Abstract Full Text Full Text PDF PubMed Scopus (290) Google Scholar; Macaulay et al. Macaulay et al., 1999Macaulay V Richards M Hickey E Vega E Cruciani F Guida V Scozzari R et al.The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs.Am J Hum Genet. 1999; 64: 232-249Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar); at any event, they occur throughout western Eurasia. The more recent “rare substitutions,” which have evolved since the earlier dispersals and which Simoni et al. (Simoni et al., 2000Simoni L Calafell F Pettener D Bertranpetit J Barbujani G Geographic patterns of mtDNA diversity in Europe.Am J Hum Genet. 2000; 66: 262-278Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar) discarded as “statistical noise,” are precisely those that are most likely to show regional distributions. The exclusion of such mutations severely restricts the capacity to identify phylogeographic units and, thus, is bound to have seriously reduced the power of the approach to detect autocorrelation. Even when haplogroup assignment is done with care, failure to detect significant clines in haplogroup frequencies does not prove the absence of any spatial structure in the mtDNA pool. Such structure would rather be manifest at a phylogenetically finer scale (defined on the basis of more-recent mutations). In any case, one would not expect that meaningful patterns of mtDNA diversity could emerge from analyses based on categories with no demonstrable phylogenetic support.
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