An international publication, led by a researcher from the Institut Pasteur, provides the most comprehensive chronology of genetic adaptations in the Latin American population, before and after the arrival of Europeans.
New genetic analyses of Latin Americans have revealed numerous insights into how indigenous peoples evolved before European contact, and how their genetics changed in recent centuries. Using a novel technique to pick apart genetic signatures of indigenous Americans, the international research team identified genetic adaptations in immunity-related genes that occurred after contact between indigenous Americans and Europeans. The latter brought with them many infectious diseases to which the native populations had not been able to adapt, such as smallpox and measles.
These new data, published in the journal Molecular Biology and Evolution, also reveal adaptive variants at a gene associated with pre-eclampsia, a high blood pressure disorder that occurs during pregnancy. These mutations could have helped Andean people avoid complications during pregnancy, which are more likely to occur at high altitudes.
A groundbreaking study of the genetic heritage of early Americans
Using a new statistical model, the authors of the study scanned the genomes of 4000 volunteers from the CANDELA consortium cohort, recruited in Brazil, Colombia, Chile, Mexico, and Peru. They were able to detect signals of ancient adaptations, focusing particularly on subjects with a higher proportion of indigenous ancestry. Until now, indigenous Americans have been severely underrepresented in genomic studies. This technique makes it possible to explore adaptations in past populations without ancient DNA, which is not easily available. The researchers were thus able to determine whether adaptations occurred only in the early Americans or in the mixed population after contact with Europeans about 500 years ago. In this way, they estimated the pressure that European diseases put on the American population.
Previous work on HLA genes on chromosome 6, which are involved in the immune response, has shown that Latin Americans have a high level of African ancestry in this genetic region. African populations displaced during the Atlantic trade appear to have carried adaptive variants in the gene pool that helped Latin American populations cope with emerging diseases. The new results of this study are consistent with this hypothesis.
Natural selection of immunity-related genes
The researchers also identified signs of significant European ancestry in the CD101 gene, which plays an important role in the regulation of inflammation. Variants from African and European populations thus helped American populations adapt to Old World infectious pathogens.
The first author of the study, Javier Mendoza-Revilla, from the Institut Pasteur's Human Evolutionary Genetics Unit, also affiliated with the Universidad Peruana Cayetano Heredia (Peru) and having started his work at the University College London (UK), points out that "these results are extremely interesting, as previous studies have shown that the inflammatory response varies from one human population to another. This highlights the evolutionary trade-off between a strong inflammatory response to fight pathogens and avoidance of the consequences of acute or chronic inflammation." The diseases brought by Europeans would therefore have had a significant impact on the immune system of today's Latin Americans. "This could have consequences, for example, on the risk of developing autoimmune diseases."
The study also found, for the first time, signs of selection before contact with Europeans, on two other genes involved in the immune response, CD300LF and MIF. These genes are notably involved in the macrophage immune response, one of the pathways of inflammation. They may have evolved in a coordinated manner to cope with the new pathogens that the first inhabitants of America encountered when they arrived.
Adaptations to reduce the risk of pregnancy complications
Living at high altitude can have an impact on health and consequences on pregnancy, due to the lack of oxygen. Indeed, altitude is a risk factor for high blood pressure during pregnancy, a disorder called pre-eclampsia. Despite this danger, some populations, such as those in the Andes, have lived at altitude for thousands of years.
The strongest evolutionary selection signal detected in the study was identified in Peruvians with indigenous American ancestors. The study shows that variants of the STOX1 gene, which is associated with preeclampsia in women of European descent, are also associated with preeclampsia in Andean populations, but are found with a much lower frequency. Over the course of the evolutionary history of Latin Americans, the pregnancy complications induced by this gene would therefore have gradually led to a decrease in its frequency in the population. The researchers now want to continue studying this evolutionary history to understand how selection pressures still impact the current health of these populations.
Disentangling Signatures of Selection Before and After European Colonization in Latin Americans, Molecular Biology and Evolution, April 19, 2022
Javier Mendoza-Revilla1,2,3, J. Camilo Chacón-Duque4,5, Macarena Fuentes-Guajardo6, Louise Ormond1, Ke Wang7, Malena Hurtado3, Valeria Villegas3, Vanessa Granja3, Victor Acuña-Alonzo8, Claudia Jaramillo9, William Arias9, Rodrigo Barquera Lozano7,8, Jorge Gómez-Valdés8, Hugo Villamil-Ramírez10,11, Caio C. Silva de Cerqueira12, Keyla M. Badillo Rivera13, Maria A. Nieves-Colón14, Christopher R. Gignoux15, Genevieve L. Wojcik16, Andrés Moreno-Estrada17, Tábita Hunemeier12, Virginia Ramallo12,18, Lavinia Schuler-Faccini12, Rolando Gonzalez-José18, Maria-Cátira Bortolini12, Samuel Canizales-Quinteros10,11, Carla Gallo3, Giovanni Poletti3, Gabriel Bedoya9, Francisco Rothhammer19, David Balding1,20, Matteo Fumagalli21, Kaustubh Adhikari22, Andrés Ruiz-Linares1,23,24, Garrett Hellenthal1
1 - Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London,
2 - Human Evolutionary Genetics Unit, Institut Pasteur, UMR2000, CNRS, Paris, France
3 - Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú
4 - AQ2 Centre for Palaeogenetics, Stockholm, Sweden
5 - Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden
6 - Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Tarapacá, Arica, Chile
7 - Department of Archaeogenetics, Max Planck Institute for the Science of Human History, Jena, Germany
8 - National Institute of Anthropology and History, Mexico City, Mexico
9 - GENMOL (Genética Molecular), Universidad de Antioquia, Medellín, Colombia
10 - Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina
Genómica, Mexico City, Mexico
11 - Universidad Nacional Autónoma de México e Instituto Nacional de Medicina Genómica, Mexico City, Mexico
12 - Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
13 - Department of Genetics, Stanford School of Medicine, Stanford, CA, USA
14 - Department of Anthropology, University of Minnesota Twin Cities, Minneapolis, MN, USA
15 - University of Colorado Anschutz Medical Campus, Aurora, CO, USA
16 - Bloomberg School of Public Health, John Hopkins University, Baltimore, MD, USA
17 - Laboratorio Nacional de Genómica para la Biodiversidad (UGA-LANGEBIO), CINVESTAV, Irapuato, Guanajuato, Mexico
18 - Instituto Patagónico de Ciencias Sociales y Humanas-Centro Nacional Patagónico, CONICET, Puerto Madryn, Argentina
19 - Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile
20 - Schools of BioSciences and Mathematics & Statistics, University of Melbourne, Melbourne, Australia
21 - School of Biological and Behavioural Sciences, Queen Mary University of London, London, United Kingdom
22 - School of Mathematics and Statistics, Faculty of Science, Technology, Engineering and Mathematics, The Open University,
Milton Keynes, United Kingdom
23 - Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and
Development, Fudan University, Shanghai, China
24 - Aix-Marseille Université, CNRS, EFS, ADES, Marseille, France