http://www.ncbi.nlm.nih.gov/pmc/article … 11-103.pdf
Current Genomics, 2010, 11, 103-114 103
1389-2029/10 $55.00+.00 ©2010 Bentham Science Publishers Ltd.
The Origin of Amerindians and the Peopling of the Americas According to
HLA Genes: Admixture with Asian and Pacific People
A. Arnaiz-Villena*,1, C. Parga-Lozano1, E. Moreno2, C. Areces1, D. Rey1 and P. Gomez-Prieto1
1Department Immunology, University Complutense, The Madrid Regional Blood Center, Madrid, Spain
2Department Surgery and Liver Transplant, Hospital 12 de Octubre, Madrid, Spain
Abstract: The classical three-waves theory of American peopling through Beringia was based on a mixed anthropological
and linguistic methodology. The use of mtDNA, Y chromosome and other DNA markers offers different results according
to the different markers and methodologies chosen by different authors. At present, the peopling of Americas remains uncertain,
regarding: time of population, number of peopling waves and place of peopling entrance among other related issues.
In the present review, we have gathered most available HLA data already obtained about First Native American
populations, which raise some doubts about the classical three waves of American peopling hypothesis. In summary, our
conclusions are: 1) North West Canadian Athabaskans have had gene flow with: a) close neighboring populations, b)
Amerindians, c) Pacific Islanders including East Australians and d) Siberians; 2) Beringia was probably not the only entrance
of people to America: Pacific Ocean boat trips may have contributed to the HLA genetic American profile (or the
opposite could also be true); 3) Amerindians entrance to America may have been different to that of Athabaskans and Eskimos
and Amerindians may have been in their lands long before Athabaskans and Eskimos because they present and altogether
different set of HLA-DRB1 allele frequencies; 4) Amerindians show very few “particular alleles”, almost all are
shared with other Amerindians, Athabaskans and Pacific Islanders, including East Australians and Siberians; 5) Our results
do not support the three waves model of American peopling, but another model where the people entrance is not only
Beringia, but also Pacific Coast. Reverse migration (America to Asia) is not discarded and different movements of people
in either direction in different times are supported by the Athabaskan population admixture with Asian-Pacific population
and with Amerindians, 6) HLA variability is more common than allele veriability in Amerindians. Finally, it is shown that
gene genealogy analises should be completed with allele frequency analyses in population relatednes and migrations studies.
Received on: November 01, 2009 - Revised on: December 01, 2009 - Accepted on: December 08, 2009
Keywords: Aleuts, Amerindians, Athabaskans, Eskimo, HLA, peopling of America, mtDNA, Y Chromosome.
INTRODUCTION
The First Amerindian Natives are postulated to have come from Asia through the Bering land bridge between 30,000–12,000 years before the present (BP). These conclusions
have been based on cultural, morphological and genetic similarities between American and Asian populations. Both Siberia [1] and Mongolia [2,3] have been put forward
as the most likely places of origin in Asia. Greenberg first postulated the triple migration theory Fig. (1) for explaining the peopling of the Americas [4]: Amerindians
(most North and South American Indians; 12,000 years BP), Na-Dene (Athabascans, Navajo, Apache; 8,000 years BP) and Eskimo-Aleuts (6,000 years BP). Research carried
out before the widespread use of Y Chromosome (Y Chr) and other nuclear DNA markers including mtDNA [5] for the study of populations [6,7] supported the three-wave
model. However, other mtDNA studies have not [8,9]; other authors postulate only one wave coming from Mongolia /North China as giving rise to the First Native American
*Address correspondence to this author at the Departamento de Inmunologia, Facultad de Medicina, Universidad Complutense, Pabellon 5, planta 4.
Avda. Complutense s/n, 28040 Madrid, Spain; Tel: +34 913 941632;
Fax: +34 91 301 73 56; E-mail: aarnaiz@med.ucm.es
ancestors [2,3].
The study of Y Chromosome DNA markers seemed to suggest the existence of a single major paternal haplotype in both North and South American Native populations
[10,11]. However, other studies on Y Chromosome show that more than one paternal founder haplotypes arrived in America during different migrations [12], probably from
Siberia [13]. See also Fig. (1) [14-17]. More recently, new mtDNA analysis has suggested that all mtDNA lineages must have been isolated in Asia before
entering the New World by at least 7-15 thousand years. They even suggest that this place must have been Beringia [18]. Also, a dispersal of Amerindians coming from Asia has
been put forward through Coastal Pacific line [19] based on all available archaeological, anthropological and mtDNA and genetic data. All these calculations are done by using paternal (Y Chr)
or maternal (mtDNA) lineages may be biased when populations displacements are concerned, as in the putative Amerindians displacement from Asia to the Americas. In addition,
other authors [20] using nuclear histocompatibility (HLA) markers do not regard as important and possible to establish the number and timing of migration waves. The important
issue is whether immigrants (Amerindians) were already differentiated (in Asia) into such ethnic groups whose descendants are still to be found in Asia. If they were differentiated
then the question of how and when they crossed the
Bering Land Bridge is a secondary one [20].
Y Chr and mtDNA studies seem unable to resolve this question, mainly because the studies have been gene- rather than population- based. Their emphasis has been on variant
genealogies rather than on population frequencies studies. In this regard HLA data may be more informative [20] because maternal and paternal lineages and both frequencies (i.e.:
genetic distances, dendrograms and correspondence analyses) and genealogies (quasi-specific HLA alleles and haplotypes) may be studied for comparing populations.
Alu-insertion investigations have also been carried out to ascertain the origin of First Americans [21]. The results are not concordant with the multiple-wave migration hypothesis;
a surprisingly short genetic distance between Chinese and Native Americans was found and explained by a recent gene flow from Asia [21].
A Trans-Pacific route of American peopling from Asia or Polynesia has been suggested because HTLV-1 virus strains shared identical sequences in Japan and in the northern coast
of South America [22] and some HLA alleles may have been introduced by the same Trans-Pacific route [15]. Finally, both genetic [17] and archaeological [16] evidence suggests
that a two-way Trans-Atlantic traffic occurred before Columbus discovered America Fig. (1); archaeologists in New Mexico have recently found tools used 20,000 years ago in
Spanish Solutrean culture [16]. All these discrepancies and uncertainties about Amerindian origins may be due to methodological (sampling) differences and also to the different genealogical history of each
genetic marker and/or to the phylogenetic usefulness of different DNA markers. For instance, functional molecules — cytochrome (cyt) b mtDNA— are used against an admixture
of intronic and exonic DNA markers, as in the Alu or STR studies: the obtained molecular genetics history could not be
the same one. In addition, population movements should be studied like a “group of genes” movements, i.e.: with gene frequencies (genetic distances, dendrograms and correspondence
analyses), which better reflect a population displacement and other populations (Asian / Amerindian) relatedness, and afterwards completed with genealogies (quasispecific HLA alleles, HLA haplotypes, mtDNA and Y Chr markers).
Thus, in the present work, we have studied the North, Meso and South American Amerindians’ HLA gene frequencies and compared it with those of other North American Indians and worldwide populations, particularly with
Asian and Pacific populations. Also, we have studied the following Amerindian ethnic groups: Seri, Mixe, Mixtecans, Zapotecans, Guaranis [23], Lakota Sioux [24], Mazatecans [25], Teeneks [26], Mayans [27], Kogi, Arsario, Arhuacs,
Wayu [28], Cayapa [29], Lamas [30], Aymaras [31], Quechuans [32], Terena Indians [33], Xavantes, Mayos [34], Uros [35], Nahuas [36], Tarahumaras [37], Toba Pilaga, Mataco Wichi, Eastern Toba [15], Mexican Mestizos and
Jaidukama (unpublished results) and also Aleuts [14]. Our aims are: 1) To determine the HLA class I (A and B) and class II (DRB1 and DQB1) quasi-specific Amerindian allelic lineages (hereafter ‘‘alleles’’ for simplicity) or specific
HLA haplotypes by using DNA sequencing and serology; in other words, the most frequent HLA alleles and haplotypes in Amerindians which do not exist or exist in very low frequency in other populations, i.e.: genealogy
comparisons and 2) To compare the Amerindians HLA allele frequencies with those of other First American Natives (Na-Dene, Eskimo and Aleuts) and also those of other worldwide populations in order to clarify the still unclear peopling of
the Americas and the origins of Amerindians, i.e.: groups of genes comparisons by using genetic distances, Neighbor Joining (NJ) dendrograms and correspondence analyses.
RESULTS AND DISCUSSION
DRB1 Alleles and HLA-Extended Haplotypes: North-American and Meso / South-American Populations
The low number of class I alleles found may be artificial, since many of them may not have been yet detected. In fact, many more HLA Class I alleles are defined at present day (wwwanthonynolan.org.uk).
We have chosen DRB1 alleles because many populations are typed for DRB1 high resolution alleles and very few for HLA class I or other class II loci. No completely specific DRB1 alleles are found in North or South American populations:
some of the alleles are found in other populations in a very low frequency Fig. (2), footnote, [38]. At the moment, the only exceptions are DRB1*0411 and DRB1*0417 alleles, which are only found in all studied Meso and
South Amerindians (Table 1), Fig. (2), bold red color (wwwantonynolan.org.uk), compared to previous times.
Notwithstanding, some Meso and South American DRB1 Amerindian alleles tend to be quasi-specific Table 1, Fig. (2), red color, but not North American alleles which are clearly shared with other non-Amerindian populations Fig.(2), blue color.
This is concordant with the existence of gene flow between Amerindians and Pacific or Siberian people, but not necessarily with a migration of Amerindians from Asia or Pacific Areas, although there are signs of cultural or genetic contacts with Asia [19] or even with Iberians
[16,17], Fig. (1). DRB1*0802 and DRB1*0407 are present in all the most frequent Meso-American haplotypes Fig. (2).
DRB1*0802 is also present in Siberian Eskimos and Japanese Ainu: otherwise it is present in almost all Amerindians.
DRB1*0407 is present in almost all Amerindian populations and absent or in a non-significant frequency in other populations.
DRB1*0403 is present in one South American most frequent haplotype Fig. (2) but also is found in high frequency throughout Pacific Islands (Samoa, Papua New Guinea, New Zealand Maories, Taiwan, Tonga, Cook Islands)
[38]. A Pacific gene flow in either direction may not be discarded by this genealogy approach also; HLA frequency data (elaborated in dendrograms and correspondence analyses) separate more Amerindians from other populations Figs. (3, 4), see below).
DRB1*0407 is an Amerindian allele in one of the most frequent South American Amerindian (Table 1) [39-57 and previous references], Fig. (2), bold red colour [58].
Both genealogy (extended haplotypes, HLA-A,-B,-DRB1,-DQB1) and allele frequency in population analyses (Correspondence and NJ multidimensional populations relatedness) have been carried out.
a. North-Americans
The relatively low number of class I alleles found some years ago in Amerindians [57] compared to other worldwide populations may be due to the fact that techniques were not by then detecting new class I alleles and many of the alleles had not yet been described.
Fig. (2) shows that the most frequent extended haplotypes in North Americans are specific for North American populations, Yupik (Eskimos), Aleuts and one of the five most frequent haplotypes are also found in Taiwan and Japanese populations (A*24-B*40-DRB1*1401-DQB1*0503).
This shows that a low degree of North American haplotypes sharing is found between North American and Asian-Pacific populations. However, there is a clear genetic HLA relatedness between isolated populations close to Beringia: Eskimos, Udegeys, Nivkhs (North East coast of Siberia) and
Koryaks and Chukchi from extreme North East Siberia Figs. (3, 4, 5), and North West American populations: Athabaskan, Alaskan Eskimos (Yupik) and Tlingit.
These results in which class II high resolution alleles and also specific class I-class II extended haplotypes are used suggest that admixture occurred between extreme North East Siberian groups and North American Na-Dene (including Tlingit) and Eskimo (Yupik) people. However, results do not
indicate anything about direction of admixture or whether migrations in both directions occurred.
On the other hand, Asian populations which are geographically not close to Beringia (Japanese, Ainu, Manchu, Singapore Chinese, Buyi) do not cluster with North Americans neither in NJ dendrogram Fig. (3) or correspondence analysis Fig. (4).
Finally, Lakota-Sioux Amerindians which have inhabited in North United States, are not related with Asians and West Siberians Figs. (3, 4, 5) but with Meso and South Americans.
Table 1. Populations Studied in the Present Work. A Total of 14,698 Chromosomes were Analyzed
Fig. (2). Geography of the most frequent HLA-DRB1 alleles and HLA extended haplotypes (the latter are ordered by frequency) in indigenous
populations of America. Most frequent North American DRB1 alleles are represented in blue. “Specific alleles” are highlighted in red.
Specific alleles in fact, are “quasi-specific” alleles (see [58]) being found in a very low frequency in Amerindian neighbouring populations,
other North American Amerindians, Pacific Islanders, Eskimos, Athabaskans, East Asians (Ainu, Japanese). DRB1*0411 and DRB1*0417
are found in Meso and South American Amerindians (represented in bold red colour). aYupik (9.3%); Aleuts (6.9%). bAleuts (8.3%). cAleuts
(6.9%); Yupik (5.4%); Taiwan (6.0%); Inuit and Japanese. dYupik (6.6%). eYupik (6.0%). fSeri (18.2%); Teeneks (15.5%); Mayans (10.6%);
Mayos (7.3%); Mixtecans (3%); Mazatecans (2.5%); Aymaras (1.7%); Peruvians (1.7%). gMazatecans (10.8%); Mixe (9%); Mayans (4.2%);
Teeneks (3.7%); Terena Indians (2.3%). hAymaras (10.4%); Mayans (8.4%); Nahuas (6.1%); Mixtecans (6%); Tarahumara (3.4%); Seri
(4.5%); Yupik (3.1%); Zapotecans (3%); Mixe (1.5%). iMayos (8.2%); Mazatecans (3.3%). jMayans (6.4%); Teeneks (5.2%). kUros (13.5%);
Aymaras (10.4%); Peruvians (9.6%); Mayans (8.4%); Quechuas (6.5%); Nahuas (6.1%); Mixtecans (6%); Seri (4.5%); Tarahumara (3.4%);
Zapotecans (3%); Mixe (1.5%). lAinu (8.0%); Quechuas (4.3%); Mayans (0.7%). mUros (6.8%); Mixtecans (5%); Mayans (4.2%); Teeneks
(3.7%); Aymaras (3.1%); Lamas (2.4%); Seri (2.3%); Terena Indians (2.3%); Quechuans (2.2%). nUros (6.3%); Quechuans (2.9%); Mayans
(0.7%). oLamas (5.9%); Aymaras (2.3%) Mayans (0.7%).
See references: [14,25-27,30-37,58].
It was considered for figure elaboration: 1) Most frequent extended four loci haplotypes in North America were taken from Aleuts [14];
Lakota-Sioux [24] and Yupik [58]. The five most frequent ones were chosen from each population; 2) Most frequent DRB1 alleles in North
America were taken (all) from Athabaskans, Canadian Penutians, Tlingit [55], Lakota-Sioux [24], Yupik [58], Aleuts [14] and Zuni. They are
represented in blue color; 3) Most frequent extended four loci haplotypes in Meso and South America were taken from Arnaiz-Villena
et al. papers (Table 1); 4) Most frequent DRB1 alleles in Meso and South American Amerindians were taken from Table 1 (Arnaiz-Villena
et al. papers) and see [58]. Highest frequencies DRB1 alleles found were: DRB1*0301, 0401, 0402, 0403, 0404, 0407, 0411, 0417, 1301,
1402, 1406, 1602, 0802 and 0901.
b. Meso-Americans
Most frequent haplotypes Fig. (2), relatedness dendrograms Fig. (3) and correspondence Fig. (4) do not relate these Amerindians with any Asian population, including North East Siberians. Haplotypes of Meso-Americans are
shared with other Amerindians and one of them with Alaskan Eskimo (Yupik): A*02-B*35-*DRB1*0802-DQB1 *0402.
c. South-Americans
These Amerindian speaking groups are related to other South-American Amerindians and to Meso-American Amerindians
Figs. (3, 4). Most frequent haplotypes are shared with other American Amerindians, but not with Asians Fig.(2).
In summary, the general view after analyzing the most frequent extended haplotypes (genealogy) is that Amerindians
have little relatedness with Asians; this is also confirmed by allele frequencies in populations and the derived analyses, Figs. (3, 4).
Genealogy studies are less suitable for comparing and relating groups of people [20]. Also, comparing HLA four loci most frequent extended haplotypes of North- Americans only share one haplotype (A*24-B*40-DRB1*1401-DQB1*0503) with Taiwanese and Japanese in
low frequencies see Fig. (2) footnote.
Specific Extended Haplotypes for Amerindian Ethnic Groups and Aleuts Some new extended four loci haplotypes have been found only in Amerindian and Aleut specific groups and in no other either Amerindians or World populations (Table 2).
It is striking that in small groups of people apparently specific HLA four loci recombinations occur and are fixed. The evolutive forces to achieve an appropriate extended haplotype may be advantageous for a population to deal with its specific environmental pathogens [59]. In this case, evolu-
Fig. (3). Neighbor-Joining dendrogram based on HLA-DRB1 allele frequencies. The genetic relatedness among Amerindians, Na-Dene,
Eskimos, Asians, Negroids, Europeans and Polynesians are determined by calculating the genetic distances between populations (DA), using
HLA-DRB1 allele frequencies. Amerindians cluster together and separated from the rest of the World populations [14,34,35,37].
Отредактировано Hăva (2011-02-20 10:40:20)
