The study, led by Elena Bosch, Principal Investigator of the IBE (CSIC-UPF), and Andrés Moreno-Estrada, Principal Investigator of CINVESTAV (UGA-LANGEBIO), authored by the IBE researcher Rocío Caro-Consuegra, gathers samples from 286 Peruvian men and women belonging to the three ecological regions (or ecoregions) of Peru. As a result of the analysis of the variation of their genomes, the researchers found evidence of genetic adaptation to the extreme altitude, the climate, and the pathogens that coexist in these environments.

Native American populations differentially adapted to the different environmental conditions of Peru

Peru has a great diversity of ecosystems that can be grouped into three ecological regions: the arid Pacific coast, the Andes mountains, and the Amazon jungle. These ecoregions are well-defined in the territory and differ in climate, topography, and vegetation. That allowed the investigation to hypothesize that the Native American populations probably had to adapt to these different environments when they arrived in Peru thousands of years ago.

The ancestors of Native American populations are believed to have diverged from East Asians around 23,000 years ago and entered the Americas through the Bering Strait, from where they began to spread throughout the Americas. Thanks to the genetic differences detected in this study, we now know that these populations adapted to life in the high Andes or to pathogens from the Amazon and the Pacific coast.

The heights of the Andes shaped the genetics of its human population

The study found genetic evidence that the Peruvian population settled in the Andes benefited from genetic changes that allowed life at high altitudes, where the oxygen concentration is lower due to a drop in the atmospheric pressure. To make up for this lack of oxygen in the blood, the human body tends to increase the breathing rate and generate an excess of red blood cells to be able to transport oxygen enough to the tissues and organs of the body. However, the increase in red blood cells increases the viscosity of the blood, which can make it difficult to pump blood and increases stress on the cardiovascular system.

In previous investigations, various adaptations of the respiratory system had already been found in Andean populations to compensate for this lower oxygen availability. This study also found positive selection signals in genes related to cardiovascular muscle and heart development, which could compensate for the stress suffered by high blood viscosity.

“There is no doubt that the hypoxia associated with the high altitude of the Andes is a very important selective pressure, and thanks to this study, we have identified the molecular footprint of the genetic adaptations that favored the survival of its population and that we observe today in the offspring.” Concludes Elena Bosch, Principal Investigator of the IBE (CSIC-UPF) who has led the study.

In addition, the study also found genetic adaptations related to skin pigmentation and lipid and glucose metabolism.

The arid Pacific coasts and the Amazon rainforest also required genetic adaptation

In the case of the Pacific and Amazonian populations, many of the genetic adaptations identified in the study are related to the immune system, possibly due to selective pressure exerted by pathogens in the area.

Some of the genes identified in the study are involved in the innate immune response, which intervenes in infectious processes in a non-specific way. In addition to other adaptive immune responses, specific genes have been linked to defense against group B streptococci, gut bacteria that can sicken newborns or adults with chronic conditions. However, many of these adaptations to pathogens were found in all three ecoregions.

The genetics of the populations of Peru help tell the story of their migrations

Although the study expected to find different genetic adaptations among the three ecoregions, some shared adaptations were found, which could reveal part of the adaptation and migration history of Peruvian populations. However, the researchers point out that it is difficult to determine the exact cause of these similarities.

“On the one hand, an ancestral population could have suffered all these selective pressures before dispersing in the three ecoregions, during its migration through the Americas. On the other hand, these adaptations may have been acquired through the relationship between the native populations of each ecoregion, and the consequent gene flow, over time. Likewise, they could also come from some selective pressures shared in more than one ecoregion due to, for example, the same pathogen.” Rocío Caro-Consuegra, currently a researcher at VHIO and the first study author, points out.

Identified genetic adaptations to altitude may help understand altitude sickness

The genetic adaptations to hypoxia found in the study may help to understand the cause of some problems associated with altitude sickness detected among the immigrant population in Peru. Coming from geographic regions at sea level or low altitude, these people do not have centuries of adaptation in their genetic heritage.

Reference article: Rocio Caro-Consuegra, Maria A Nieves-Colón, Erin Rawls, Verónica Rubin-de-Celis, Beatriz Lizárraga, Tatiana Vidaurre, Karla Sandoval, Laura Fejerman, Anne C Stone, Andrés Moreno-Estrada, Elena Bosch, Uncovering Signals of Positive Selection in Peruvian Populations from Three Ecological Regions, Molecular Biology and Evolution, Volume 39, Issue 8, August 2022, msac158, https://doi.org/10.1093/molbev/msac158