Pablo Gomez-Prieto

The Origin of Amerindians and the Peopling of the Americas According to HLA Genes: Admixture with Asian and Pacific People

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.

HLA genes in Uros from Titikaka Lake, Peru: origin and relationship with other Amerindians and worldwide populations

Uros population from the Titikaka Lake live in about 42 floating reed (‘totora’) islands in front of Puno City (Peru) at a 4000 m high altiplano. They present both an mtDNA and a human leucocyte antigen (HLA) profile different from the surrounding populations: mtDNA A2 haplogroup is common to Uros and Amazon forest lowland Amerindians. HLA genetic distances between populations have been calculated and neighbour‐joining dendrograms and correspondence analyses were carried out. Approximately 15 006 HLA chromosomes from worldwide populations have been used for comparisons. Only eight HLA‐A alleles have been found, three of them accounting for most of the frequencies. The same phenomenon is seen for HLA‐B, HLA‐DRB1 and HLA‐DQB1 alleles: a few alleles (3, 4 and 3, respectively) are present in most individuals. The presence of HLA‐B*4801 and HLA‐DRB1*0901 alleles in a relatively high frequency (although not the most frequent alleles found) is a characteristic shared with Asians and some populations from the Andean altiplano. Three specific Uros haplotypes have been found among the most frequent ones: HLA‐A*680102‐B*3505‐DRB1*0403‐DQB1*0302; HLA‐A*2402‐B*1504‐DRB1*1402‐DQB1*0301; and HLA‐A*2402‐B*4801‐DRB1*0403‐DQB1*0302. The present study suggests that Uros may have been one of the first populations from the shores of the Titikaka Lake coming from the Amazonian forest, which might have given rise to other later differentiated ethnic group (i.e. Aymaras). Uros HLA profile is also useful to study genetic epidemiology of diseases linked to HLA and to construct a future transplant waiting list by adding up regional lists in order to get a bigger pool for transplanting with better HLA matching.

HLA Genes in Afro-American Colombians (San Basilio de Palenque): The First Free Africans in America

An Afro-American semi-isolated Colombian population is studied for its HLA genes: San Basilio de Palenque community in Colombia northern mountains. This community represents the first free Africans in America earning recog- nition by the Spanish Crown in 1691 AD. Nowadays, they also speak the only extant Bantu-Spanish Creole language over the World; these people have been apart from there neighbours and claim a direct African descent. Their HLA genes were compared with African, Afro-American, Amerindian and worldwide populations by using genetic distances (DA), Neigh- bour-Joining dendograms and correspondences analyses. Arlequin, DISPAN and VISTA softwares were used for the completion of these computerised calculations. San Basilio de Palenque, a relatively ethnic isolate, is genetically close to other North and South Afro-Americans and to West Africa-Bantu speaking groups (Senegalese; Bubi, Guinea Gulf). Five HLA extended haplotypes are found only in this population: A*02-B*07-DRB1*0801-DQB1*0301, A*02-B*35- DRB1*1304-DQB1*0301, A*02-B*15-DRB1*0302-DQB1*0402, A*01-B*51-DRB1*0301-DQB1*0201, A*68-B*15- DRB1*0102-DQB1*0501. Only very limited gene flow is found from either Amerindians or Europeans, as expected by historical records. Our HLA data may also prove useful for future regional transplant programs and genetic epidemiology of HLA-linked diseases.

HLA in Jaidukama: an Amerindian secluded Colombian population with new haplotypes and Asian and Pacific-shared alleles

America first inhabitants and peopling are still debated. In order to increase knowledge about these questions, we have aimed to detect HLA genes of an Amerindian secluded community: Jaidukama, who lives in North Colombia Equatorial forest. HLA genotyping and extended haplotype calculations were carried out in 39 healthy individuals belonging to 13 families. HLA frequencies were compared to other Amerindians and worldwide populations by calculating genetic distances, relatedness dendrograms and correspondence analyses. Only four DRB1 alleles were found (*0404, *0407, *1402 and *1602); however a total of 17 Amerindian different extended class I–class II HLA haplotypes were directly counted from the family studies, nine of them were specific of Jaidukamas. Some of the alleles or group of alleles within an extended haplotype (i.e. DQB1–DRB1) were also found in Asians and Pacific Islanders, further supporting existence of Asian and Pacific gene flow with Amerindians or a common founder effect. It is further supported that HLA extended haplotypes vary faster than alleles in populations. It is concluded that this unique model of Amerindian secluded families study suggests that rapid HLA haplotype variation may be more important than allele variation for survival (starting immune responses). This work may also be useful for future transplant programs in the area.

HLA-class II genes in Mexican Amerindian Mayas: relatedness with Guatemalan Mayans and other populations.

We analyzed the HLA class II allele frequencies in 50 healthy unrelated Mayan individuals. The relationship with other worldwide populations was studied by using HLA data from 71 different populations. The most frequent alleles were HLA-DRB1*04, HLA-DRB1*01, HLA-DQB1*0302 and HLA-DQB1*0501. When comparisons with other Mexican Amerindian groups were made, some differences were observed. Mayans showed an increased frequency of HLA-DRB1*01 when compared to Nahuas, Mayos, Teenek and Mazatecans (p < 0.05), whereas the HLA-DRB1*04 was increased in Mayans when compared to Nahuas (p < 0.05). The analysis of HLA-DQB1 alleles showed an increased frequency of DQB1*0302 in Mayans when compared to Nahuas and Mazatecans (p < 0.05), whereas the frequency of HLA-DQB1*0301 was decreased in Mayans when compared to Nahuas, Mayos, Teenek and Mazatecans (p < 0.05). Decreased frequency of HLA-DQB1*0501 in Mayans when compared to Nahuas was found. Neighbour Joining dendrogram shows that Mexican Mayans are genetically close to some of the most ancient groups living in Mexico and some South American Amerindians. However, Guatemalan Mayans do not cluster together with Mexican Mayas showing that languages do not correlate with genes, particularly in Amerindians. The data corroborate the restricted polymorphism of HLA-DRB1 and DQB1 alleles and the high frequency of HLA-DRB1*04 and HLA-DQB1*0302 in Mayans from Mexico.

Evolution of major histocompatibility complex G and C and natural killer receptors in primates

Major histocompatibility complex (MHC)-G and -C molecules bear ligands to natural killer immunoglobulin receptors (KIR). MHC-G evolution in primates shows some anomalies. In New World monkeys MHC-G molecules show a high polymorphism and most likely are classical antigen presenters; they also cluster closer to MHC-E in a relatedness dendrogram. Their genes lack intron 2 deletion, which is typical of all other primates in regard to MHC-G. Medium-sized Eurasian-African monkeys (Cercopithecinae) show stop codons in exon 3: only MHC-G isoforms without exon 3 are possible. Big apes such as the orangutan, gorilla, and chimpanzee as well as human beings show limited HLA-G polymorphism. HLA-C has not been found in medium-size Eurasian-African monkeys, but we have found MHC-C DNA sequences in more evolutionary ancient New World monkeys. Taking into account that the KIR inhibitory receptors signal is dominated by MHC-C in human beings, this suggests that both MHC-C molecules and their ligands within natural killer lymphocyte KIR also exist in the most evolutionary ancient apes (New World monkeys were present on Earth before 40 million years ago), as KIR receptors also appeared before 130 million years ago in evolution. Indeed, KIR receptor genes have recently been found in a New World monkey.

HLA genes in Wayu Amerindians from Colombia

Amerindians origins and prehistory are still debated. HLA profile is different to all other World populations, although they have particular alleles in common with Asians, Australians and Pacific Islanders. In the present work, HLA-A, -B, -DRB1, -DQB1 alleles have been studied in Wayu Amerindians from Colombia. HLA alleles haplotypes, genetic distances and NJ dendrograms were calculated by Arlequin and DISPAN software. Only a few both class I and class II alleles have been observed. Most common extended haplotypes include: A*24-B*51-DRB1*0403-DQB1*0302, A*2-B*15-DRB1*1602-DQB1*0301, A*2-B*35-DRB1*0407-DQB1*0302, but also A*68-B*15-DRB1*0403-DQB1*0302. No trace of Caucasoid or Negroid admixture is detected. The Wayu HLA profile is typical from Amerindians and shows how languages and genes do not correlated particularly in this case (i.e., Wayu closest HLA genetic group is North Argentinian Guarani group). Results obtained in this work may be useful for future transplant programs and also for HLA linked diseases and individualized pharmacogenetics.

HLA Genes in Populations of the Aleutian Islands

Abstract We typed a subset of the Aleut population for HLA loci (HLA-A, HLA-B, HLA-DRB1, HLA-DQB1) to obtain an HLA profile, which was compared to other Eurasian and Amerindian populations for studying Aleut origin and its significance on the peopling of the Americas. Allele frequencies at the four loci were identified in an Aleut sample using standard indirect DNA sequencing methods. Genetic distances with Amerindians and Eurasians were obtained by comparing Aleut allele frequencies with a worldwide population database (13,164 chromosomes). The most frequently extended HLA haplotypes were also calculated. We also generated Aleut relatedness dendrograms and calculated correspondence relatedness in a multidimensional scale. Both neighbor-joining dendrograms and correspondence analysis separated Aleuts from Eskimos and Amerindians. Aleuts are closer genetically to Europeans, including Scandinavians and English. Our results are concordant with those obtained by Y-chromosome analysis, suggesting that most male Aleut ancestors of our sample came mainly from Europe.

What Might have been the Ancestor of New World Siskins?~!2008-08-04~!2008-10-29~!2008-12-05~!

Eurasian Carduelis spinus (siskin) has given rise to the C.pinus (pine siskin) North American radiation,which includes C.dominicensis, C.p. perplexus and C.atriceps . It is addressed the question why C.spinus is not thriving now in America.

Human Leukocyte Antigen-DRB1 Class II Genes in Mexican Amerindian Mazahuas: Genes and Languages Do Not Correlate

BACKGROUND The major histocompatibility complex genes are located on the short arm of the human sixth chromosome; they are highly polymorphic and therefore have been very advantageous in population genetic studies. METHODS A Mazahua group established in North Mexico State and also in nearby Michoacan state in the rainy mountain highlands (Mexico) was studied for their human leukocyte antigen (HLA)-DRB1 alleles. The relationship with other Amerindians and worldwide populations was studied by using 14,996 chromosomes from 75 different populations and calculating neighbor-joining dendrograms and correspondence multidimensional values. RESULTS Five principal HLA allele frequencies were found in our group: DRB1*0802 (the most frequent one in this population), DRB1*0407, DRB1*0403, DRB1*0101, and DRB1*1406. Both genetic distances and correspondence analyses clearly show that our Mazahua group is genetically close to some of the most ancient groups living in Mexico (Mayos, Zapotecans, Tennek) and South American Amerindians. Amerindians remain as a group apart from the rest of the world. CONCLUSIONS The results analyzing the HLA-DR locus suggest that Mazahua language (Otomangue) does not correlate with those of the most closely HLA-correlated ethnic groups. The present data may be useful for future transplantation programs, HLA and disease diagnosis, and pharmacogenetic studies.