Evolutionary mismatch and the role of GxE interactions in human disease

Lea AJ 1 , Clark AG 2 , Dahl AW 3 , Devinsky O 4 , Garcia AR 5 , Golden CD 6 Show all authors , Kamau J 7 , Kraft TS 8 , Lim YAL 9 , Martins D 10 , Mogoi D 11 , Pajukanta P 12 , Perry G 13 , Pontzer H 14 , Trumble BC 15 , Urlacher SS 16 , Venkataraman VV 17 , Wallace IJ 18 , Gurven M 19 , Lieberman D 20 , Ayroles JF 21

Affiliations 

  • 1 Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA
  • 2 Department of Computational Biology, Cornell University, Ithaca, NY, USA
  • 3 Section of Genetic Medicine, University of Chicago, Chicago, IL, USA
  • 4 Department of Neurology, NYU Langone Medical Center, New York, NY, USA
  • 5 Center for Evolution and Medicine, Arizona State University, Tempe, United States
  • 6 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  • 7 Department of Biochemistry, School of Medicine, University of Nairobi, Nairobi, Kenya
  • 8 Department of Anthropology, University of Utah, Salt Lake City, USA
  • 9 Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
  • 10 Turkana Basin Research Institute, Turkana, Kenya
  • 11 Director at County Government of Laikipia, Nanyuki, Kenya
  • 12 Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
  • 13 Department of Anthropology, Pennsylvania State University, University Park, PA, USA
  • 14 Evolutionary Anthropology, Duke University, Durham, NC, USA
  • 15 School of Human Evolution and Social Change, Arizona State University, Tempe, US
  • 16 Department of Anthropology, Baylor University, Waco, TX, USA
  • 17 Department of Anthropology and Archaeology, University of Calgary, Calgary, Canada
  • 18 Department of Anthropology, University of New Mexico, Albuquerque, USA
  • 19 Department of Anthropology, University of California: Santa Barbara, Santa Barbara, CA, USA
  • 20 Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA
  • 21 Department of Ecology and Evolution, Princeton University, Princeton, NJ, USA
ArXiv, 2023 Feb 13.
PMID: 36713247

Abstract

Globally, we are witnessing the rise of complex, non-communicable diseases (NCDs) related to changes in our daily environments. Obesity, asthma, cardiovascular disease, and type 2 diabetes are part of a long list of "lifestyle" diseases that were rare throughout human history but are now common. A key idea from anthropology and evolutionary biology-the evolutionary mismatch hypothesis-seeks to explain this phenomenon. It posits that humans evolved in environments that radically differ from the ones experienced by most people today, and thus traits that were advantageous in past environments may now be "mismatched" and disease-causing. This hypothesis is, at its core, a genetic one: it predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions and have differential health effects in ancestral versus modern environments. Here, we discuss how this concept could be leveraged to uncover the genetic architecture of NCDs in a principled way. Specifically, we advocate for partnering with small-scale, subsistence-level groups that are currently transitioning from environments that are arguably more "matched" with their recent evolutionary history to those that are more "mismatched". These populations provide diverse genetic backgrounds as well as the needed levels and types of environmental variation necessary for mapping GxE interactions in an explicit mismatch framework. Such work would make important contributions to our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and sociocultural contexts.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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