Rewriting Human History and Empowering Indigenous Communities with Genome Editing Tools

Abstract

Appropriate empirical-based evidence and detailed theoretical considerations should be used for evolutionary explanations of phenotypic variation observed in the field of human population genetics (especially Indigenous populations). Investigators within the population genetics community frequently overlook the importance of these criteria when associating observed phenotypic variation with evolutionary explanations. A functional investigation of population-specific variation using cutting-edge genome editing tools has the potential to empower the population genetics community by holding “just-so” evolutionary explanations accountable. Here, we detail currently available precision genome editing tools and methods, with a particular emphasis on base editing, that can be applied to functionally investigate population-specific point mutations. We use the recent identification of thrifty mutations in the CREBRF gene as an example of the current dire need for an alliance between the fields of population genetics and genome editing.

“Where do I even start?” Recommendations for faculty diversifying syllabi in ecology, evolution, and the life sciences

“…Here we have provided a framework to create more diverse and anti‐colonial syllabi by establishing a professional learning process that we have found through our own experience aids individual instructors through collective efforts. A more diverse and holistic understanding of ecology, evolution, and allied fields can be the first step in helping future professionals to address disparities and damaging practices that are still prevalent in their fields (Fox et al, 2020 ; Hoffman et al, 2016 ; Khan & Mian, 2020 ; Ortega & Roby, 2021 ), work to remove barriers for minoritized students and faculty in STEM (Cheung et al, 2021 ; Kiesling et al, 2020 ; Miriti, 2020 ) and provide land management plans and inclusive ecological practices and studies (Schell et al, 2020a ) that support people and the environment without replicating past harms (Frainer et al, 2020 ; Trisos et al, 2021 ). Furthermore, we propose that efforts based on collaboration and communal support (Tzou et al, 2019 ), increasing longevity and effectiveness of these efforts.…”

Seq-ing Higher Ground: Functional Investigation of Adaptive Variation Associated With High-Altitude Adaptation

“…While physiologically relevant isogenic cell lines combined with genome-editing technology offer great insight into some of the biological mechanisms involved in high-altitude adaptive phenotypes, we recognize that evaluations of function and mechanism require consideration of environmental pressure(s) at high altitude (Fox et al, 2020). During hypoxia, HIF transcription factors are stabilized and regulate various genes such as those involved in oxygen transport, and there are multiple methods used in laboratory settings to induce hypoxia in physiologically relevant cell cultures (Wu and Yotnda, 2011).…”

“…The potential to engineer new tools to functionally investigate genetic variation is an exciting prospect as it establishes greater accountability in research (e.g., in population genetics, reducing the tendency toward evolutionary adoptionism narratives (Gould et al, 1979). While some researchers overlook the importance of oral history, ethnography, linguistic, and archeological data when drawing conclusions about phenotypic observations and evolutionary analyses (e.g., GWAS and polygenic risk scores) (Nielsen, 2009), it is important to recognize that Indigenous populations should be included in the co-development of evolutionary and medically actionable narratives surrounding human genetic variation collected in their community (Jackson et al, 2019;Fox et al, 2020). Additionally, echoing previous observations by Lewinton and Gould, both 'empirical evidence and detailed theoretical considerations' should be used for evolutionary explanations of phenotypic variation observed in various Indigenous populations (Claw et al, 2018).…”

Base Editing in Human Cells to Produce Single‐Nucleotide‐Variant Clonal Cell Lines

“…Indeed, although there are currently over 685 million human SNVs identified in the dbSNP database (Sherry et al, 2001), <1% have a defined clinical interpretation in ClinVar (Landrum et al, 2018). This issue is particularly endemic to rare genetic variants and those discovered in minoritized populations and indigenous people (1000Genomes Project Consortium et al, 2015Fox, Rallapalli, & Komor, 2020;Popejoy & Fullerton, 2016), highlighting the need for a significant increase in studies that can functionally assess human genetic variants in laboratory settings. At the core of these studies is the ability to introduce genetic variants in living cells with high efficiency and precision, something that can be accomplished using baseediting technologies.…”