The genomes of Mexico's native peoples reveal evolutionary adaptations and challenges to global change

Mexico's indigenous ethnic groups are particularly vulnerable to modern lifestyle and dietary changes. In some cases, they inherited biological adaptations developed over millennia by their ancestors that might be no longer playing an advantageous role and posing a risk to their health.

This is shown by the results of a new international study coordinated by researchers at the University of Bologna published in the journal Molecular Biology and Evolution and to which another journal, Nature Ecology & Evolution, dedicated a “Research Highlight”. Researchers analysed the genome of about three hundred individuals belonging to 15 Mexican ethnic groups to trace their evolutionary histories and understand how these may have influenced their different adaptive potential to global changes.

"We focused especially on non-admixed indigenous populations whose genetic heritage could represent as close an approximation as possible to that of the populations of the main Mexican pre-Columbian civilisations, including Mayans and Aztecs", explains Marco Sazzini, professor at the Department of Biological, Geological and Environmental Sciences of the University of Bologna and study coordinator. "This allowed us to examine the genetic bases of the specific biological characteristics of these peoples that had been evolving in their ancestors over thousands of years well before the arrival of Europeans on the American continent."

BIOLOGICAL ADAPTATIONS AND GLOBAL CHANGE: AN EVOLUTIONARY APPROACH
Through the action of natural selection, these populations evolved biological peculiarities allowing them to adapt over time to environmental and social conditions in which their civilisations developed. Nevertheless, modern radical transformations of these conditions and global changes, which are still taking place today, were so rapid that further adaptations were not possible.

The results obtained by researchers show that numerous biological characteristics of native Mexican peoples, including susceptibility to certain diseases, have been variously influenced by their complex and diverse evolutionary history. This dataset could now prove useful in the development of targeted medical actions.

"The data collected can be used to develop prevention initiatives targeted at each ethnic group following a precision medicine approach," confirms Claudia Ojeda Granados, first author of the study and post-doctoral fellow at the University of Bologna with a grant from the National Council of Science and Technology (CONACyT) of Mexico.

"Studies like this one prove the effectiveness of an evolutionary approach to the study of diseases. Such an approach is not alternative to that of biomedical research, but it is instead complementary to it", adds Professor Sazzini. "This is indeed useful for further understanding the risks that environmental, ecological and cultural changes experienced in modern times by our planet and all its populations pose to human health."

DIFFERENT ENVIRONMENTS AND CULTURES SHAPE DIFFERENT BIOLOGICAL TRAITS
Researchers analysed the genome of about three hundred individuals belonging to 15 Mexican ethnic groups and identified several macro-groups of genetically homogeneous populations. Thus, it was possible to examine populations with an allegedly common evolutionary history on an aggregate basis: peoples who lived for thousands of years in contiguous geographical regions, experienced very similar environmental conditions and social organisations, and developed a dense network of migrations and trades.

“These studies showed that Seri and Rarámuri – two ethnic groups from different regions of Northern Mexico – as well as five populations originating in central regions – including the Nahua who descend from the Aztecs – and eight populations inhabiting the southern regions – including descendants of the ancient Mayans and Zapotecs – had independent histories of biological adaptation to their ecological and cultural environments,” explains Andrés Moreno-Estrada, principal investigator at the National Laboratory of Genomics for Biodiversity at Cinvestav (Mexico), who also contributed to the research.

For instance, on the one hand, Seri showed particular modifications in several genes involved in sugar metabolism, in physiological processes related to sweet taste perception, and in the regulation of blood glucose levels. These characteristics probably evolved in response to a diet based mainly on fruit, seeds and succulent plants until the middle of the 20th century. In short, this might have represented a way of reducing risks associated with a diet rich in sugars.

Rarámuri, on the other hand, are a semi-nomadic group that covers long distances during seasonal movements and their primary source of food is corn. In their genome, researchers identified unique combinations of variants in genes regulating energy metabolism, oxygen consumption and body temperature during intense and sustained physical exertion. Researchers also identified genetic changes enhancing the functioning of the intestinal barrier, i.e. the layer of gut cells responsible for ensuring nutrient absorption and blocking harmful substances from entering the circulatory system. The intestinal barrier is the main target of mycotoxins developing when corn is stored for an extended period of time.

Genetic adaptations observed in the populations of Central Mexico were instead found to be disadvantageous for contemporary lifestyles. The regular consumption of psychoactive plants endemic to these regions and of fermented alcoholic beverages in religious practices and traditional medicine has indeed resulted in the maintenance, over millennia, of variants on genes encoding metabotropic glutamate and dopamine receptors and modulating the inhibitory mechanisms of the corresponding neurotransmission systems. These properties have increased tolerance to the harmful effects of these substances, although they confer a higher risk of developing addictions. This risk was exacerbated by the recent disruption of traditional diets, which resulted in increased consumption of alcohol and foods that may lead to the development of pathological addictions.

Finally, ethnic groups native to Southern Mexico show combinations of genetic variants ameliorating immune responses against pathogens endemic to this geographical area, such as the trypanosome and the protozoan responsible for Chagas disease and cutaneous leishmaniosis, respectively. Unlike several populations of South America in which these diseases are widespread and often carry dangerous consequences, infected individuals in the populations of Southern Mexico do not generally present severe comorbidities in the case of Chagas disease or may even develop an asymptomatic form of leishmaniosis.

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THE AUTHORS OF THE STUDY
The study was published in the journal Molecular Biology and Evolution under the title "Dietary, Cultural and Pathogens-related Selective Pressures Shaped Differential Adaptive Evolution Among Native Mexican Populations" and coordinated by Marco Sazzini, professor at the Department of Biological, Geological, and Environmental Sciences (BiGeA) of the University of Bologna, who is belonging also to the Alma Mater Research Institute on Global Challenges and Climate Change.

The first author of this paper is Claudia Ojeda-Granados. She received a two-year postdoctoral fellowship from the National Council of Science and Technology (CONACyT) of Mexico to take part in the project conducted in Bologna at the BiGeA Centre for Genome Biology and in partnership with the graduate program in Integrative Biology of Cinvestav, Mexico. BiGeA researchers of the University of Bologna Stefania Sarno, Paolo Abondio and Sara De Fanti also contributed to the study.

Finally, Alice Setti from the Department of Cellular, Computational and Integrative Biology of the University of Trento (Italy), Guido Alberto Gnecchi Ruscone from the Max Planck Institute for Evolutionary Anthropology in Leipzig (Germany), Héctor Rangel-Villalobos from the University of Guadalajara (Mexico), Eduardo González-Orozco, Andres Jiménez-Kaufmann and Andrés Moreno-Estrada from the National Laboratory of Genomics for Biodiversity of Cinvestav (Mexico) collaborated in the research.

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