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

JACOVAS, VC; ROVARIS DIEGO LUIZ ; PERÉZ ORLANDO ; DE AZEVEDO SOLEDAD ; SOUZA MACEDO GABRIEL ; SANDOVAL JOSÉ RAUL ; SALAZAR-GRANARA ALBERTO ; VILLENA MERCEDES ; DUGOUJON JEAN-MICHEL ; BISSO-MACHADO RAFAEL ; PETZL- ERLER MARIA LUIZA ; SALZANO FRANCISCO MAURO ; ASHTON-PROLLA, P; RAMALLO VIRGINIA ; BORTOLINI MARIA CÁTIRA

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2015 p. 1 - 15

1932-6203

The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway(TP53, rs1042522; MDM2, rs2279744; MDM4, rs1563828; USP7, rs1529916; andLIF, rs929271) were studied in a total of 282 individuals belonging to Quechua, Aymara,Chivay, Cabanaconde, Yanke, Taquile, Amantani, Anapia, Uros, Guarani Ñandeva, andGuarani Kaiowá populations, characterized as Native American or as having a high level (>90%) of Native American ancestry. In addition, published data pertaining to 100 personsfrom 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 inlowlands (< 2,500 m). Our analyses revealed that alleles USP7-G, LIF-T, and MDM2-Tshowed significant evidence that they were selected for in relation to harsh environmentalvariables related to high altitudes. Our results show for the first time that alleles of classicalTP53 network genes have been evolutionary co-opted for the successful human colonizationof the Andes.