To Trust or Not to Trust an Idiosyncratic Mitochondrial Data Set
2003; Elsevier BV; Volume: 72; Issue: 5 Linguagem: Inglês
10.1086/375119
ISSN1537-6605
AutoresYong‐Gang Yao, Vincent Macaulay, Toomas Kivisild, Ya‐Ping Zhang, Hans‐Jürgen Bandelt,
Tópico(s)Genomics and Phylogenetic Studies
ResumoTo the Editor: In a recent report, Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar) provided partial (8.8 kb) information on the mtDNA coding region (within the region 7148–15946, in the numbering of the Cambridge reference sequence [CRS]; Anderson et al. [Anderson et al., 1981Anderson S Bankier AT Barrell BG de Bruijn MH Coulson AR Drouin J Eperon IC Nierlich DP Roe BA Sanger F Schreier PH Smith AJ Staden R Young IG Sequence and organization of the human mitochondrial genome.Nature. 1981; 290: 457-465Crossref PubMed Scopus (7183) Google Scholar]) in 40 individuals from Brazil. On the basis of the similarity in nucleotide diversity and age estimates of the four founder haplogroups A, B, C, and D, they claimed to have added new evidence for a single early entry of the founder populations into America. However, a site-by-site audit of the data reveals that their sequences are not of high enough quality to justify such statements. The authors failed to realize that a large number of mutations associated with basal branches of the worldwide mtDNA phylogeny (Finnilä et al. Finnilä et al., 2001Finnilä S Lehtonen MS Majamaa K Phylogenetic network for European mtDNA.Am J Hum Genet. 2001; 68: 1475-1484Abstract Full Text Full Text PDF PubMed Scopus (285) Google Scholar; Maca-Meyer et al. Maca-Meyer et al., 2001Maca-Meyer N González AM Larruga JM Flores C Cabrera VC Major genomic mitochondrial lineages delineate early human expansions.BMC Genetics. 2001; 2: 13Crossref PubMed Scopus (252) Google Scholar; Torroni et al. Torroni et al., 2001Torroni A Rengo C Guida V Cruciani F Sellitto D Coppa A Luna Calderon F Simionati B Valle G Richards M Macaulay V Scozzari R Do the four clades of the mtDNA haplogroup L2 evolve at different rates?.Am J Hum Genet. 2001; 69: 1348-1356Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar; Derbeneva et al. Derbeneva et al., 2002Derbeneva OA Sukernik RI Volodko NV Hosseini SH Lott MT Wallace DC Analysis of mitochondrial DNA diversity in the Aleuts of the Commander Islands and its implications for the genetic history of Beringia.Am J Hum Genet. 2002; 71: 415-421Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar; Herrnstadt et al. Herrnstadt et al., 2002Herrnstadt C Elson JL Fahy E Preston G Turnbull DM Anderson C Ghosh SS Olefsky JM Beal MF Davis RE Howell N Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.Am J Hum Genet. 2002; 70 (71:448–449 (erratum)): 1152-1171Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar; Kivisild et al. Kivisild et al., 2002Kivisild T Tolk H-V Parik J Wang Y Papiha SS Bandelt H-J Villems R The emerging limbs and twigs of the East Asian mtDNA tree.Mol Biol Evol. 2002; 19: 1737-1751Crossref PubMed Scopus (326) Google Scholar) were not correctly scored in their data set. In the case of the hypervariable segments of the mtDNA control region, Bandelt et al. (Bandelt et al., 2001Bandelt H-J Lahermo P Richards M Macaulay V Detecting errors in mtDNA data by phylogenetic analysis.Int J Legal Med. 2001; 115: 64-69Crossref PubMed Scopus (161) Google Scholar, Bandelt et al., 2002Bandelt H-J Quintana-Murci L Salas A Macaulay V The fingerprint of phantom mutations in mitochondrial DNA data.Am J Hum Genet. 2002; 71: 1150-1160Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar) have highlighted lab-specific idiosyncrasies through comparative phylogenetic analysis. For the coding region, the task of identifying anomalies and reconstructing their potential causes is somewhat easier because the vast majority of sites there do not appear to undergo frequent mutations. The coding region well supports a basal nesting of (monophyletic) haplogroups, many of which had already been identified through RFLP analysis and sequencing of the hypervariable segments (Richards and Macaulay Richards and Macaulay, 2001Richards M Macaulay V The mitochondrial gene tree comes of age.Am J Hum Genet. 2001; 68: 1315-1320Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar). For example, the basal division of Eurasian mtDNAs into macrohaplogroups M and N is amazingly clear cut. The Eurasian mtDNA phylogeny that emerges from the phylogenetic analysis of the complete mtDNA database is detailed (for east Asia) in figure 1 of Kivisild et al. (Kivisild et al., 2002Kivisild T Tolk H-V Parik J Wang Y Papiha SS Bandelt H-J Villems R The emerging limbs and twigs of the East Asian mtDNA tree.Mol Biol Evol. 2002; 19: 1737-1751Crossref PubMed Scopus (326) Google Scholar), which attempts a reconstruction of the mutational history. The African mtDNA phylogeny has also been well documented in recent papers (Maca-Meyer et al. Maca-Meyer et al., 2001Maca-Meyer N González AM Larruga JM Flores C Cabrera VC Major genomic mitochondrial lineages delineate early human expansions.BMC Genetics. 2001; 2: 13Crossref PubMed Scopus (252) Google Scholar; Torroni et al. Torroni et al., 2001Torroni A Rengo C Guida V Cruciani F Sellitto D Coppa A Luna Calderon F Simionati B Valle G Richards M Macaulay V Scozzari R Do the four clades of the mtDNA haplogroup L2 evolve at different rates?.Am J Hum Genet. 2001; 69: 1348-1356Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar; Herrnstadt et al. Herrnstadt et al., 2002Herrnstadt C Elson JL Fahy E Preston G Turnbull DM Anderson C Ghosh SS Olefsky JM Beal MF Davis RE Howell N Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.Am J Hum Genet. 2002; 70 (71:448–449 (erratum)): 1152-1171Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar). Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar) reported 40 mtDNAs, of which they assigned 31 to the Native American haplogroups A, B, C, and D (according to their fig. 1). The remaining nine mtDNAs can be assigned unambiguously to the Asian haplogroups B4 and D4, the Eurasian haplogroup U, and the African haplogroup L2a (table 1), as we will argue below. Figure 1 displays the truncation (relative to the 8.8-kb fragment under study) of the rooted phylogeny that is relevant for assigning these 40 mtDNAs to their respective haplogroups. This phylogeny is unanimously supported by the earlier publications. (However, note that mutations at 15301 and 11944 were not reconstructed most parsimoniously along the African mtDNA tree shown in fig. 1 of Herrnstadt et al. [Herrnstadt et al., 2002Herrnstadt C Elson JL Fahy E Preston G Turnbull DM Anderson C Ghosh SS Olefsky JM Beal MF Davis RE Howell N Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.Am J Hum Genet. 2002; 70 (71:448–449 (erratum)): 1152-1171Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar]). The only instances of recurrent mutations (real or not) for the mutations and haplogroups highlighted in figure 1 are then as follows: the transversion 15487T is missing in the single haplogroup C lineage of Maca-Meyer et al. (Maca-Meyer et al., 2001Maca-Meyer N González AM Larruga JM Flores C Cabrera VC Major genomic mitochondrial lineages delineate early human expansions.BMC Genetics. 2001; 2: 13Crossref PubMed Scopus (252) Google Scholar); in the data of Herrnstadt et al. (Herrnstadt et al., 2002Herrnstadt C Elson JL Fahy E Preston G Turnbull DM Anderson C Ghosh SS Olefsky JM Beal MF Davis RE Howell N Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.Am J Hum Genet. 2002; 70 (71:448–449 (erratum)): 1152-1171Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar), the B4b lineage 375 has experienced a transition at 14766, the L2a lineage 223 lacks the 7521 transition, and the 14566 transition is missing in the L2a lineage 165, which is closely related to another L2a lineage (bearing the 14566 mutation) from Torroni et al. (Torroni et al., 2001Torroni A Rengo C Guida V Cruciani F Sellitto D Coppa A Luna Calderon F Simionati B Valle G Richards M Macaulay V Scozzari R Do the four clades of the mtDNA haplogroup L2 evolve at different rates?.Am J Hum Genet. 2001; 69: 1348-1356Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar) in that they both share additional mutations at 3010 and 6663.Table 1Sequence Variation in 40 Samples Reported by Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar)Sample IDHaplogroupSequence on Region 7148–15976aAll bear 14766 in addition.Basal Mutations MissedbBasal polymorphisms that were undetected or omitted by Silva et al. (2002), including 11719 and the two rare mutations (8860 and 15326) in the CRS.Accession NumberGRC0149A7369 7522G 8027 8794 886011335 12007 12705 15326 1552411719AF465949KTN0130A8794 8860 11129 11288 11719 12007 12406 12705 14178 14755 1486115326AF465956KPO0013A8764 8794 9392 9966 11335 11719 12007 12292G 12314G 12705 13708 145668860 15326AF465957PTJ0003A8794 11719 11944 12007 127058860 15326AF465962WTE1182A8794 8860 11617G 11719 12007 12292G 12618 12705 15326…AF465972WPI0167A8794 8860 10398 11719 12007 12705 1497815326AF465974YAN0623A8794 8860 10694 11719 12007 12705 13928C 15317 15326…AF465975YAN0665A8794 8860 11719 12007 12705 13928C15326AF465976KCR0029A8794 8860 9192 103981040011335 12007 12314G 1270511719 15326AF465950GRC0169B4b7626 8860 9950 11335 11719 11821 13590 15326 155358281–8289delAF465953KTN0209B4b8860 11150 11719 13590 14645 14647 15535 15914C8281–8289del 15326AF465955KPO0001B4b7369 7522G 8281–8289del 8860 9950 11335 11719 13590 1553515326AF465958KPO0039B4b8736 8860 9950 10954 11335 11719 13590 155358281–8289del 15326AF465959KPO0023B4b8552 10604 11719 13590 13708 155358281–8289del 8860 15326AF465960QUE1876B4b8020 8860 11335 11719 12618 135908281–8289del 15326 15535AF465964QUE1881B4b8860 9950 11335 11719 1359015043155358281–8289del 15326AF465965YAN0637B4b8860 9950 11177 11719 12155C 13590 13708 15106 155358281–8289del 15326AF465980KRC0033B4b7227T 7251 8860 9950 103981040011335 11719 135908281–8289del 15535 15326AF465951QUE1880B4b7231C 8860 9950 103981040011335 11719 12192 13590 153268281–8289del 15535AF465968JAP1044B4c/B4a1011510238del 10398 11335 11719 15326 153468281–8289del 8860AF465948ARL0058C7196A 8078 8584 8701 9540 9545 10398 10400 10873 11719 11914 12705 13263 14783 15043 15301 153268860 14318 15487TAF465945PTJ0068C8701 8860 9540 9545 10873 11719 11914 12705 13263 14318 14783 14788 15043 15914C7196A 8584 10398 10400 15301 15487T 15326AF465961QUE1875C7196A 8584 8701 8860 9540 954511335 11719 11914 12705 13263 13656 14783 15043 1530110398 10400 10873 14318 15487T 15326AF465966QUE1878C8584 8701 9540 9545 10873 11335 11719 11914 12705 13263 13545 14783 15043 151917196A 8860 10398 10400 14318 15301 15487T 15326AF465967YAN0669C8701 8848 8860 9540 9545 10310 10398 10400 11719 11914 12705 13263 13326 14318 14783 15043 153267196A 8584 10873 15301 15487TAF465977YAN0591C8584 8701 8848 8860 9540 9545 10873 11719 11914 12705 13263 13326 14783 150437196A 10398 10400 14318 15301 15487T 15326AF465978YAN0650C7196A 8701 8848 8860 9540 9545 10398 10873 11617G 11719 11914 12705 13263 13326 14318 14783 15043 153018584 10400 15487T 15326AF465979JAP1045D48701 8860 8964 9296 9540 9824A 10115 10398 10873 11719 12705 14783 15043 15301 153268414 10400 14668AF465947GRC0131D48701 8860 9540 10816T 10873 11335 11914 12705 13059 13067 14783 150438414 10398 10400 11719 14668 15301 15326AF465952JAP1043D48701 8860 9540 10398 10400 10873 11215 11719 12705 14783 15043 15301 15326 158748414 14668AF465946KTN0018D8701 8860 9540 10873 10874 12705 14687 14783 1504310398 10400 11719 15301 15326AF465954PTJ0001D8701 8860 9540 10398 10400 10873 11150 11719 12705 14783 15043 15106 1530115326AF465963TYR0004D8701 8860 9540 10398 10400 11719 12406 12705 12810 1530110873 14783 15043 15326AF465969TYR0016D8701 8860 10398 10400 10819 10873 10874 11719 12406 12705 128109540 14783 15043 15301 15326AF465970NGR0524L2a7175 7256 7274 7521 8047del 8701 8860 9221 9540 10115 10398 10873 11719 11914 11944 12314G 12693 12705 13590 136507771 8206 13803 14566 15301 15326 15784AF465941NGR0522L2a7256 7274 7521 7771 8701 8860 9221 9540 10873 10994C 11029T 11335 11719 11914 11944 12292G 12693 12705 13590 13650 13803 1578415802del 15848del7175 8206 10115 10398 14566 15301 15326AF465942NGR0475L2a7175 7256 7274 7521 7771 8701 8860 9221 9540 10373 10873 11719 11914 11944 12693 12705 13590 13650 1380314668157848206 10115 10398 14566 15301 15326AF465943NGR0510L2a7256 7274 7521 7771 8701 8860 9221 9540 10115 10398 10873 11617G 11719 11914 11944 12693 12705 13590 13650 13803 157847175 8206 14566 15301 15326AF465944WTE1150L2a7175 7256 7274 7521 7771 8701 8860 9221 10115 10398 10873 11335 11719 11914 11944 12693 12705 13194 13590 13650 13803 15301 15326 157848206 9540 14566AF465973WTE1145U7220A 7227T 7642 8860 9668 11467 11719 12308 1237213590 15326…AF465971Note.—Sites are numbered according to the revised reference sequence (Andrews et al. Andrews et al., 1999Andrews RM Kubacka I Chinnery PF Lightowlers RN Turnbull DM Howell N Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA.Nat Genet. 1999; 23: 147Crossref PubMed Scopus (2376) Google Scholar); suffixes A, G, C, and T indicate transversions; “del” indicates a deletion. The mutations in boldface distinguish each sequence from the nearest mtDNA ancestor of haplogroups L2′3, M, N, and R. Potential reading errors or possible phantom mutations are italicized and underlined.a All bear 14766 in addition.b Basal polymorphisms that were undetected or omitted by Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar), including 11719 and the two rare mutations (8860 and 15326) in the CRS. Open table in a new tab Note .—Sites are numbered according to the revised reference sequence (Andrews et al. Andrews et al., 1999Andrews RM Kubacka I Chinnery PF Lightowlers RN Turnbull DM Howell N Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA.Nat Genet. 1999; 23: 147Crossref PubMed Scopus (2376) Google Scholar); suffixes A, G, C, and T indicate transversions; “del” indicates a deletion. The mutations in boldface distinguish each sequence from the nearest mtDNA ancestor of haplogroups L2′3, M, N, and R. Potential reading errors or possible phantom mutations are italicized and underlined. It is conspicuous that in all five haplogroup L2a mtDNAs of Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar), two of the basal transitions, 8206 and 14566, characteristic of L2 and L2a, respectively, are missed. Further L2a-diagnostic mutations, such as 7175, 7771, 13803, and 15784, are not always reported in the sequences (table 1). Moreover, the five L2a lineages have a total of only 11 other (private) mutations, comprising as many as five transversions, four deletions, and only two transitions. This pattern of private mutations differs from that in the three L2a lineages (nine transitions and no other mutations) of Ingman et al. (Ingman et al., 2000Ingman M Kaessmann H Pääbo S Gyllensten U Mitochondrial genome variation and the origin of modern humans.Nature. 2000; 408: 708-713Crossref PubMed Scopus (984) Google Scholar) and Torroni et al. (Torroni et al., 2001Torroni A Rengo C Guida V Cruciani F Sellitto D Coppa A Luna Calderon F Simionati B Valle G Richards M Macaulay V Scozzari R Do the four clades of the mtDNA haplogroup L2 evolve at different rates?.Am J Hum Genet. 2001; 69: 1348-1356Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar) in the same mtDNA region. It thus looks as though most of the real private mutations in the L2a mtDNAs were missed and that, instead, phantom mutations were scored. The basal mutation 15487T of haplogroup M8 (which embraces haplogroups C and Z) is omitted in all seven C lineages of Silva et al.’s data (table 1). Other basal mutations for haplogroup C lineages are missing at sites 7196A, 8584, and 14318, in different combinations. It is remarkable that even deep mutations, such as 10400, 10873, and 15301 that distinguish macrohaplogroups M and N, were overlooked in six of the seven C lineages. Among the seven D lineages in Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar), three sequences share mutations or motifs with D sequences reported elsewhere (Ingman et al. Ingman et al., 2000Ingman M Kaessmann H Pääbo S Gyllensten U Mitochondrial genome variation and the origin of modern humans.Nature. 2000; 408: 708-713Crossref PubMed Scopus (984) Google Scholar; Derbeneva et al. Derbeneva et al., 2002Derbeneva OA Sukernik RI Volodko NV Hosseini SH Lott MT Wallace DC Analysis of mitochondrial DNA diversity in the Aleuts of the Commander Islands and its implications for the genetic history of Beringia.Am J Hum Genet. 2002; 71: 415-421Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar). The sequence JAP1045 (from an individual of Japanese origin) shares 8964, 9296, and 9824A with a Japanese mtDNA sequence from Ingman et al. (Ingman et al., 2000Ingman M Kaessmann H Pääbo S Gyllensten U Mitochondrial genome variation and the origin of modern humans.Nature. 2000; 408: 708-713Crossref PubMed Scopus (984) Google Scholar) and, therefore, definitely belongs to haplogroup D4, although the two characteristic D4 transitions (8414 and 14668) are not reported in the entire data set, except for one occurrence of 14668 in an L2a sequence! Similarly, the Japanese mtDNA sequence JAP1043 bears one of the mutations, 11215, found in Siberian mtDNAs of haplogroup D4 (Ingman et al. Ingman et al., 2000Ingman M Kaessmann H Pääbo S Gyllensten U Mitochondrial genome variation and the origin of modern humans.Nature. 2000; 408: 708-713Crossref PubMed Scopus (984) Google Scholar; Derbeneva et al. Derbeneva et al., 2002Derbeneva OA Sukernik RI Volodko NV Hosseini SH Lott MT Wallace DC Analysis of mitochondrial DNA diversity in the Aleuts of the Commander Islands and its implications for the genetic history of Beringia.Am J Hum Genet. 2002; 71: 415-421Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar). The Guarani sequence GRC0131 of Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar) shares a rare transversion 10816T and a rare transition 13059 with the Guarani sequence of Ingman et al. (Ingman et al., 2000Ingman M Kaessmann H Pääbo S Gyllensten U Mitochondrial genome variation and the origin of modern humans.Nature. 2000; 408: 708-713Crossref PubMed Scopus (984) Google Scholar), but only the latter one has 8414 and 14668 and is thus confirmed as belonging to D4. These cases provide strong evidence for the systematic oversight of the basal mutations 8414 and 14668 in all haplogroup D lineages from Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). Just as in the case of haplogroup C, several of the basal mutations that separate M and N are also missing in most of the D lineages. Anomalies are also found in the nine sequences belonging to haplogroup A, although it was claimed by Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar) to be “the most homogeneous and best characterized” cluster in figure 1. Sample KCR0029 contains basal mutations 10398 and 10400 for haplogroup M. Sample KPO0013 has the 14566 mutation that is characteristic of haplogroup L2a. Sample PTJ0003 bears the L2abc-specific mutation 11944. Moreover, site 8027 is found mutated in only one A lineage, whereas this mutation was present in all the A sequences in Herrnstadt et al. (Herrnstadt et al., 2002Herrnstadt C Elson JL Fahy E Preston G Turnbull DM Anderson C Ghosh SS Olefsky JM Beal MF Davis RE Howell N Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.Am J Hum Genet. 2002; 70 (71:448–449 (erratum)): 1152-1171Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar) and in one Chukchi sequence reported by Ingman et al. (Ingman et al., 2000Ingman M Kaessmann H Pääbo S Gyllensten U Mitochondrial genome variation and the origin of modern humans.Nature. 2000; 408: 708-713Crossref PubMed Scopus (984) Google Scholar). In the 11 B lineages, only sample KPO0001 has the 9-bp deletion in the COII/tRNALys intergenic region, characteristic of haplogroup B. One or both of the basal mutations of B4b, 13590 and 15535, occur in all the samples (with the exception of JAP1044) and hint that they belong to B4b. It should be noted that in Herrnstadt et al. (Herrnstadt et al., 2002Herrnstadt C Elson JL Fahy E Preston G Turnbull DM Anderson C Ghosh SS Olefsky JM Beal MF Davis RE Howell N Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.Am J Hum Genet. 2002; 70 (71:448–449 (erratum)): 1152-1171Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar), mutations 9950 and 11177 further defined a subhaplogroup of B4b that was baptized “B2.” We suggest that the 11177 mutation could have been omitted by Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar) as well. The Japanese B lineage JAP1044 could belong to haplogroup B4c or, alternatively, to B4a, as judged by the 15346 mutation or the 10238 transition, respectively (if the latter was simply misreported as a deletion). Two samples, KRC0033 and QUE1880, bear the 10400 mutation of haplogroup M, whereas sample QUE1881 harbors the 15043 mutation of M. The U sequence in Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar) contains the full motif of haplogroup U, plus two transversions and three transitions not previously found in the published U sequences (Ingman et al. Ingman et al., 2000Ingman M Kaessmann H Pääbo S Gyllensten U Mitochondrial genome variation and the origin of modern humans.Nature. 2000; 408: 708-713Crossref PubMed Scopus (984) Google Scholar; Finnilä et al. Finnilä et al., 2001Finnilä S Lehtonen MS Majamaa K Phylogenetic network for European mtDNA.Am J Hum Genet. 2001; 68: 1475-1484Abstract Full Text Full Text PDF PubMed Scopus (285) Google Scholar; Maca-Meyer et al. Maca-Meyer et al., 2001Maca-Meyer N González AM Larruga JM Flores C Cabrera VC Major genomic mitochondrial lineages delineate early human expansions.BMC Genetics. 2001; 2: 13Crossref PubMed Scopus (252) Google Scholar; Herrnstadt et al. Herrnstadt et al., 2002Herrnstadt C Elson JL Fahy E Preston G Turnbull DM Anderson C Ghosh SS Olefsky JM Beal MF Davis RE Howell N Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.Am J Hum Genet. 2002; 70 (71:448–449 (erratum)): 1152-1171Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar). Rare deletions are found in two L2a and one B lineage of Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). The 15802delA and 15848delA in the cytochrome b gene of sample NGR0522, 8047delT in the COII gene of sample NGR0524, and 10238delT in the ND3 gene of sample JAP1044 generate premature stop codons in these genes. These rare deletions all occur at a 2-bp repeat of the deleted base and might be generated by the Sequencer reading program. It is clear that the sequences of Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar) harbor more rare transversions and fewer private transitions than other reported sequences (Ingman et al. Ingman et al., 2000Ingman M Kaessmann H Pääbo S Gyllensten U Mitochondrial genome variation and the origin of modern humans.Nature. 2000; 408: 708-713Crossref PubMed Scopus (984) Google Scholar; Finnilä et al. Finnilä et al., 2001Finnilä S Lehtonen MS Majamaa K Phylogenetic network for European mtDNA.Am J Hum Genet. 2001; 68: 1475-1484Abstract Full Text Full Text PDF PubMed Scopus (285) Google Scholar; Maca-Mayer et al. Maca-Meyer et al., 2001Maca-Meyer N González AM Larruga JM Flores C Cabrera VC Major genomic mitochondrial lineages delineate early human expansions.BMC Genetics. 2001; 2: 13Crossref PubMed Scopus (252) Google Scholar; Torroni et al. Torroni et al., 2001Torroni A Rengo C Guida V Cruciani F Sellitto D Coppa A Luna Calderon F Simionati B Valle G Richards M Macaulay V Scozzari R Do the four clades of the mtDNA haplogroup L2 evolve at different rates?.Am J Hum Genet. 2001; 69: 1348-1356Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar; Herrnstadt et al. Herrnstadt et al., 2002Herrnstadt C Elson JL Fahy E Preston G Turnbull DM Anderson C Ghosh SS Olefsky JM Beal MF Davis RE Howell N Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.Am J Hum Genet. 2002; 70 (71:448–449 (erratum)): 1152-1171Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar). One cannot exclude the possibility that true transitions were erroneously scored as transversions or deletions by Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). The two rare mutations 8860 and 15326 of the CRS are also missed in most of the sequences. The mutation 11335 in the CRS, which was found to be a sequencing error (Andrews et al. Andrews et al., 1999Andrews RM Kubacka I Chinnery PF Lightowlers RN Turnbull DM Howell N Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA.Nat Genet. 1999; 23: 147Crossref PubMed Scopus (2376) Google Scholar), was present in 16 mtDNAs. Processes that could account for these anomalies include the following: 1.Only one strand of mtDNA was sequenced;2.Sequences were aligned with some variant of the CRS (a likely source of problems in the past; see Macaulay et al. [Macaulay et al., 1999Macaulay V Richards M Sykes B Mitochondrial DNA recombination: no need to panic.Proc R Soc Lond B. 1999; 266: 2037-2039Crossref PubMed Scopus (45) Google Scholar]);3.Sequences from different samples, especially those belonging to different haplogroups, were aligned together during the editing process (In this way, one might easily “borrow” a fragment of one sample into another when the sequences of the latter were not overlapping and, thus, introduce basal polymorphisms of one mtDNA lineage into another);4.Possible sample crossover or contamination during data collection;5.Relying just on the sequence scored by the Sequencer reading program without further manual checking of the chromatogram, especially relevant in the case of the rare deletions; and/or6.PCR errors during amplification. In summary, we have every reason to mistrust the mtDNA sequences published by Silva et al. (Silva et al., 2002Silva Jr, WA Bonatto SL Holanda AJ Ribeiro-dos-Santos AK Paixão BM Goldman GH Abe-Sandes K Rodriguez-Delfin L Barbosa M Paçó-Larson ML Petzl-Erler ML Valente V Santos SEB Zago MA Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America.Am J Hum Genet. 2002; 71: 187-192Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). One cannot escape the conclusion that these data are seriously flawed or, at least, are not mtDNA as we know it.
Referência(s)