HLA-G 3'UTR haplotype frequencies in highland and lowland South Native American populations.

Human Leukocyte Antigen (HLA)-G participates in several biological processes, including reproduction, vascular remodeling, immune tolerance, and hypoxia response. HLA-G is a potential candidate gene for high altitude adaptation since its expression is modulated in both micro and macro environment under hypoxia and constant cellular stress. Besides the promoter region, the HLA-G 3'untranslated region (UTR) influences HLA-G expression patterns through several post-transcriptional mechanisms. Currently, the 3'UTR genetic diversity in terms of altitude adaptation of Native American populations is still unexplored, particularly at high altitude ecoregions. Here, we evaluated 288 Native Americans from 9 communities located in the Andes [highland (HL); ≥2,500 m (range = 2,838-4,433 m)] and 8 populations located in lowland (LL) regions [<2,500 m (range = 80-431 m); Amazonian tropical forest, Brazilian central plateau, and Chaco] of South America. In total, nine polymorphic sites and ten haplotypes were observed. The most frequent haplotypes (UTR-1, UTR-2, and UTR-3) accounted for âˆ¼ 77% of haplotypes found in LL, while in the HL, the same haplotypes reach âˆ¼ 93%. Also, a remarkable high frequency of putative ancestral UTR-5 haplotype was observed in LL (21.5%), while in HL UTR-2 reaches up to 47%. Further, UTR-2 frequency positively correlates with altitude-related variables, while a negative correlation for UTR-5 was observed. From an evolutionary perspective, we observed a tendency towards balancing selection in HL and LL populations thus suggesting that haplotypes of ancient and more derived alleles may have been co-opted for relatively recent adaptations such as those experienced by modern humans in the highland and lowland of South America. We also discuss how long-term balancing selection can be a reservoir of genetic variants that can be positively selected. Finally, our study provides some pieces of evidence that HLA-G 3'UTR haplotypes may have contributed to high altitude adaptation in the Andes.

Genetic Variations in the TP53 Pathway in Native Americans Strongly Suggest Adaptation to the High Altitudes of the Andes.

The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway (TP53, rs1042522; MDM2, rs2279744; MDM4, rs1563828; USP7, rs1529916; and LIF, rs929271) were studied in a total of 282 individuals belonging to Quechua, Aymara, Chivay, Cabanaconde, Yanke, Taquile, Amantani, Anapia, Uros, Guarani Ñandeva, and Guarani Kaiowá populations, characterized as Native American or as having a high level (> 90%) of Native American ancestry. In addition, published data pertaining to 100 persons from five other Native American populations (Surui, Karitiana, Maya, Pima, and Piapoco) were analyzed. The populations were classified as living in high altitude (≥ 2,500 m) or in lowlands (< 2,500 m). Our analyses revealed that alleles USP7-G, LIF-T, and MDM2-T showed significant evidence that they were selected for in relation to harsh environmental variables related to high altitudes. Our results show for the first time that alleles of classical TP53 network genes have been evolutionary co-opted for the successful human colonization of the Andes.

Extreme high prevalence of a defective mannose-binding lectin (MBL2) genotype in native South American West Andean populations.

Mannose-binding lectin (MBL) is one of the five recognition molecules in the lectin complement pathway. Common variant alleles in the promoter and structural regions of the human MBL gene (MBL2) influence the stability and serum concentration of the protein. Epidemiological studies have shown that MBL2 variant alleles are associated with susceptibility to and the course of different types of infectious and inflammatory conditions. However, it has been suggested that these alleles are maintained in different populations due to selected advantages for carriers. We investigated the MBL2 allelic variation in indigenous individuals from 12 different West Central South America localities spanning from the desert coast, high altitude Andean plates and the Amazon tropical forest within the territories of Peru (n = 249) (Departments of Loreto, Ucayali, Lambayeque, Junin, Ayacucho, Huancayo and Puno), and Ecuador (n = 182) (Region of Esmeraldas and Santo Domingo de los Colorados). The distribution of MBL2 genotypes among the populations showed that the defective variant LYPB haplotype was very common. It showed the highest frequencies in Puno (Taquile (0.80), Amantani (0.80) and Anapia (0.58) islander communities of the Lake Titicaca), but lower frequencies of 0.22 in Junin (Central Andean highland) and Ucayali (Central Amazonian forest), as well as 0.27 and 0.24 in the Congoma and Cayapa/Chachis populations in the Amazonian forest in Ecuador were also observed. Our results suggest that the high prevalence of the MBL2 LYPB variant causing low levels of functional MBL in serum may mainly reflect a random distribution due to a population bottleneck in the founder populations.

The genetic history of indigenous populations of the Peruvian and Bolivian Altiplano: the legacy of the Uros.

The Altiplano region of the South American Andes is marked by an inhospitable climate to which the autochthonous human populations adapted and then developed great ancient civilizations, such as the Tiwanaku culture and the Inca Empire. Since pre-Columbian times, different rulers established themselves around the Titicaca and Poopo Lakes. By the time of the arrival of Spaniards, Aymara and Quechua languages were predominant on the Altiplano under the rule of the Incas, although the occurrence of other spoken languages, such as Puquina and Uruquilla, suggests the existence of different ethnic groups in this region. In this study, we focused on the pre-Columbian history of the autochthonous Altiplano populations, particularly the Uros ethnic group, which claims to directly descend from the first settlers of the Andes, and some linguists suggest they might otherwise be related to Arawak speaking groups from the Amazon. Using phylogeographic, population structure and spatial genetic analyses of Y-chromosome and mtDNA data, we inferred the genetic relationships among Uros populations (Los Uros from Peru, Uru-Chipaya and Uru-Poopo from Bolivia), and compared their haplotype profiles with eight Aymara, nine Quechua and two Arawak (Machiguenga and Yanesha) speaking populations from Peru and Bolivia. Our results indicated that Uros populations stand out among the Altiplano populations, while appearing more closely related to the Aymara and Quechua from Lake Titicaca and surrounding regions than to the Amazon Arawaks. Moreover, the Uros populations from Peru and Bolivia are genetically differentiated from each other, indicating a high heterogeneity in this ethnic group. Finally, our results support the distinctive ancestry for the Uros populations of Peru and Bolivia, which are likely derived from ancient Andean lineages that were partially replaced during more recent farming expansion events and the establishment of complex civilizations in the Andes.

Poblamiento del continente americano y del Perú sugerido de un análisis filogeográfico de haplogrupos del mtDNA en etnias nativas I: inferencias primarias / Peopling of the American continent and Peru as suggested from a phylogeographic mtDNA haplogroups analysis in native ethnoses. I: preliminary inferences

OBJETIVOS: Precisar el origen de las poblaciones peruanas en un contexto filogeográfico, global y temporal. METODOS: Análisis comparativo de los resultados obtenidos a partir del procesamiento del mtDNA, de cinco poblaciones peruanas nativas sitas en Pucallpa, Taquile, Anapia, Amantani y Los Uros, con los resultados obtenidos por diferentes autores en la misma molécula (reciente y antigua) de 91 etnias–localidades, que incluyen varias del continente americano y algunas de nuestro país, y 13 del SE del continente asiático. Realizamos un análisis filogeográfico a partir de las frecuencias de los haplogrupos hallados por RFLPs y una secINDEL del mtDNA. Los datos fueron procesados por el programa PHYLIP 3.65 opción Distancias de Reynolds, para determinar los valores F de Diferenciación Genética o Coalescencia. El algoritmo UPGMA usó los valores de F entre pares de ST STetnias–localidades, para construir un árbol de distancias que permita el análisis de sus principales grupamientos(clusters). RESULTADOS: El árbol obtenido exhibe 7 clusters. El cluster 1 comprende a la etnia Han ubicada al SEde Asia, en tanto que las americanas se ubican entre los clusters 2 al 7. Las etnias menos diversas fueron dos: la Quechua (Taquile, Puno-Perú) – 100 por ciento haplotipo B - y la de los Kuna (Panamá) – 100 por ciento haplotipo A-.CONCLUSIONES: Los mayores valores encontrados de diferenciación genética, corresponden a los Yanomami, con un F de 0.23741, mientras que en el Perú fueron los Quechua de Taquile con un valor F de 0.16673. En ambos casos los resultados indican, según la tabla de calificación de valores F , una Divergencia Genética Alta.

OBJETIVES: To determine the origins of Peruvian populations in a more global and temporal phylogeographic context. METHODS: mtDNA results obtained in our laboratories from the analysis of the mtDNA from 5 native Peruvian populations that inhabit Pucallpa, Taquile, Anapia, Amantani and Los Uros, were compared with the results obtained different authors on the same molecule from 91 ethnoses-localities that include some of our country, others from the American continent, as well as 13 of the SE of the Asian continent. Phylogeographic analysis was done from the haplogroups frequencies found from the RFLPs and an INDEL sequence of mtDNA, and the data were processed by the program PHYLIP 3.65, option Distances of Reynolds to find F values of Genetic ST Differentiation or Coalescency. The UPGMA algorithm allowed us to express the values F between pairs of ST ethnoses-localities and to carry out the analysis of the main clusters, by means of a tree. RESULTS: The tree exhibit 7 main clusters. Cluster I comprised only the ethnos located to SE of Asia. The American ethnoses are located along the clusters 2 to 7. The less diverse ones were two: the Quechua from Taquile, (Puno-Peru) - 100 per cent B haplotype, and the Kuna from Panama, – 100 per cent A haplotype. CONCLUSIONS: Genetic differentiation larger values were in the Yanomami (0.23741) group. For Peru, they were in the Aymara ethnos from Taquile with F values of 0.16673. Both correspond to a High Genetic Divergence respect to the near closest ones.

Variantes del ADNmt en isleños del lago Titicaca: máxima frecuencia del haplotipo B1 y evidencia de efecto fundador / Variants of DNAmt among islanders of the lake Titicaca: Highest frequency of haplotype B1 and evidence of founder effect

Los polimorfismos del ADN mitocondrial son herramientas en el estudio comparativo de poblaciones modernas y antiguas. Entre los más usados están los haplotipos mitocondriales basados en RFLP (polimorfismo de longitud de fragmentos de restricción) y un sistema de inserción/delección. El presente estudio establece la frecuencia de estos haplotipos y compara un total de 144 individuos representativos de las islas Taquile y Amantaní (lengua quechua) y de las islas de Los Uros y Anapia (lengua aymara) del lago Titicaca, Perú. Nuestros resultados revelan la predominancia del haplotipo B1: 100 por ciento en Taquile (n=57); 88,6 por ciento en Amantaní (n=35); 75 por ciento en Los Uros (n=28) y 87,5 por ciento en Anapia (n=24), siendo las frecuencias más altas registradas en el mundo. Otros haplotipos se observan en menor proporción: 17,9 por ciento de A2 y 7,1 por ciento de D1 en Los Uros; 11,4 por ciento de la variante C1 en Amantaní; 4,2 por ciento de cada haplotipo C1, C2 y D1 en Anapia. La alta frecuencia de B1 indica que las poblaciones de Taquile, Amantaní y Anapia provienen de un grupo fundador reducido. Aunque hay afinidad entre las poblaciones aymaras de Anapia y Los Uros; la proporción de algunos alelos en los últimos, sugiere la persistencia de una acervo genético uru en contraposición a la idea de su extinción.