Scanning the human genome for “signatures” of positive selection: Transformative opportunities and ethical obligations

Abstract

The relationship history of evolutionary anthropology and genetics is complex. At best, genetics is a beautifully integrative part of the discipline. Yet this integration has also been fraught, with punctuated, disruptive challenges to dogma, periodic reluctance by some members of the field to embrace results from analyses of genetic data, and occasional over‐assertions of genetic definitiveness by geneticists. At worst, evolutionary genetics has been a tool for reinforcing racism and colonialism. While a number of genetics/genomics papers have disproportionately impacted evolutionary anthropology, here we highlight the 2002 presentation of an elegantly powerful approach for identifying “signatures” of past positive selection from haplotype‐based patterns of genetic variation. Together with technological advances in genotyping methods, this article transformed our field by facilitating genome‐wide “scans” for signatures of past positive selection in human populations. This approach helped researchers test longstanding evolutionary anthropology hypotheses while simultaneously providing opportunities to develop entirely new ones. Genome‐wide scans for signatures of positive selection have since been conducted in diverse worldwide populations, with striking findings of local adaptation and convergent evolution. Yet there are ethical considerations with respect to the ubiquity of these studies and the cross‐application of the genome‐wide scan approach to existing datasets, which we also discuss.

Parallel evolution in human populations: A biocultural perspective

“…Studies of genetics, development, or physiology are conducted in populations thought to be experiencing similar selective pressures, and the results compared to identify shared or similar adaptations. Genetic approaches to identifying adaptation usually rely on statistical tests that scan the genome for signals of selection 10,18 . Some of these tests infer selection by comparing allele frequencies between a population experiencing the selective pressure and a related population not experiencing it.…”

“…Other tests measure the length of haplotypes (i.e., stretches of chromosomes inherited as a unit) in the population. They infer selection on an allele when the surrounding haplotype is significantly longer than other haplotypes in the genome as haplotypes that contain beneficial alleles tend to be conserved and broken up less often by recombination 18,32 . Once putatively selective alleles are identified, functional in vitro experiments or physiological analyses are needed to determine the phenotypic effect of the allele(s) if not already known.…”

“…In each of the following examples of parallel evolution, we highlight the genetic and physiological adaptations that have been identified and discuss the cultural contexts impacting human biological variation. We do not explore the population genetic models or mathematical formulae underlying the discussed examples in depth here as they are beyond the scope of this review and have been covered elsewhere 1,4,10,18,34 . Instead, we focus on the broad patterns of parallel evolution in humans and how cultural contexts shape human evolution.…”

“…17 Modern genetic adaptation studies rely on mathematical algorithms to identify signals of natural selection in the genome, and some weave stories about the function and significance of variants identified as putatively adaptive without much knowledge of the associated phenotypes, relevant sociocultural contexts, or even whether selection or other evolutionary processes are actually responsible for the patterns of variation observed. 18 Furthermore, assuming a simple relationship between biology and the environment, where biotic environments shape genetic variation and human biologies primarily through natural selection, is problematic. Humans are not passive acceptors of our environmental circumstances 19,20 ; we manipulate our environments and behavior to create more hospitable lives in even the harshest contexts.…”

Evolutionary medicine

“…In principle, worldwide participation in scientific research and expansive sharing in its benefits can improve equity. However, researchers must pay attention to important ethical considerations, especially when partnering with Indigenous populations (Hernandez and Perry, 2021). In particular, efforts should be made to ensure that communities are fairly compensated and receive other longer-term benefits related to the knowledge and any new treatments that are developed on the basis of their participation (Fox, 2020).…”