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

Vanessa Cristina Jacovas; Diego Luiz Rovaris; Orlando Peréz; Soledad de Azevedo; Gabriel Souza Macedo; José Raul Sandoval; Alberto Salazar-Granara; Mercedes Villena; Jean-Michel Dugoujon; Rafael Bisso-Machado; Maria Luiza Petzl-Erler; Francisco Mauro Salzano; Patricia Ashton-Prolla; Virginia Ramallo; Maria Cátira Bortolini

doi:10.1371/journal.pone.0137823

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

PLoS One. 2015 Sep 18;10(9):e0137823. doi: 10.1371/journal.pone.0137823. eCollection 2015.

Authors

Vanessa Cristina Jacovas¹, Diego Luiz Rovaris¹, Orlando Peréz², Soledad de Azevedo², Gabriel Souza Macedo¹, José Raul Sandoval³, Alberto Salazar-Granara³, Mercedes Villena⁴, Jean-Michel Dugoujon⁵, Rafael Bisso-Machado¹, Maria Luiza Petzl-Erler⁶, Francisco Mauro Salzano¹, Patricia Ashton-Prolla⁷, Virginia Ramallo², Maria Cátira Bortolini¹

Affiliations

¹ Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil.
² Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Puerto Madryn, Argentina.
³ Facultad de Medicina Humana, Universidad de San Martin de Porres (USMP), Lima, Peru.
⁴ Instituto Boliviano de Biología de Altura (IBBA), Universidad Mayor de San Andres, La Paz, Bolivia.
⁵ Anthropologie Moléculaire et Imagerie de Synthèse, CNRS UMR 5288, Université Paul Sabatier Toulouse III, Toulouse, 31000, France.
⁶ Laboratório de Genética Molecular, Departamento de Genética, Universidade Federal do Paraná, Curitiba, PR, Brasil.
⁷ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acclimatization / genetics*
Altitude
Humans
Indians, North American / genetics*
Polymorphism, Single Nucleotide*
Tumor Suppressor Protein p53 / genetics*

Substances

TP53 protein, human
Tumor Suppressor Protein p53

Grants and funding

This work was supported the by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (Brazil).