title: Genetic Variations in the TP53 Pathway in Native Americans Strongly Suggest Adaptation to the High Altitudes of the Andes.
abstract: 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.
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil.
authors.forename: Vanessa Cristina
authors.initials: VC
authors.lastname: Jacovas
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil.
authors.forename: Diego Luiz
authors.initials: DL
authors.lastname: Rovaris
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Puerto Madryn, Argentina.
authors.forename: Orlando
authors.initials: O
authors.lastname: Peréz
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Puerto Madryn, Argentina.
authors.forename: Soledad
authors.initials: S
authors.lastname: de Azevedo
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil.
authors.forename: Gabriel Souza
authors.initials: GS
authors.lastname: Macedo
authors.affiliation: Facultad de Medicina Humana, Universidad de San Martin de Porres (USMP), Lima, Peru.
authors.forename: José Raul
authors.initials: JR
authors.lastname: Sandoval
authors.affiliation: Facultad de Medicina Humana, Universidad de San Martin de Porres (USMP), Lima, Peru.
authors.forename: Alberto
authors.initials: A
authors.lastname: Salazar-Granara
authors.affiliation: Instituto Boliviano de Biología de Altura (IBBA), Universidad Mayor de San Andres, La Paz, Bolivia.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Villena
authors.affiliation: Anthropologie Moléculaire et Imagerie de Synthèse, CNRS UMR 5288, Université Paul Sabatier Toulouse III, Toulouse, 31000, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dugoujon
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Bisso-Machado
authors.affiliation: Laboratório de Genética Molecular, Departamento de Genética, Universidade Federal do Paraná, Curitiba, PR, Brasil.
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Petzl-Erler
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil.
authors.forename: Francisco Mauro
authors.initials: FM
authors.lastname: Salzano
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil; Serviço de Genética Medica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Puerto Madryn, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Ramallo
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil.
authors.forename: Maria Cátira
authors.initials: MC
authors.lastname: Bortolini
mesh_terms: D000064:Acclimatization / Q000235:genetics*; D000531:Altitude; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53