Population Genomics and the Statistical Values of Race: An Interdisciplinary Perspective on the Biological Classification of Human Populations and Implications for Clinical Genetic Epidemiological Research

Abstract

The biological status and biomedical significance of the concept of race as applied to humans continue to be contentious issues despite the use of advanced statistical and clustering methods to determine continental ancestry. It is thus imperative for researchers to understand the limitations as well as potential uses of the concept of race in biology and biomedicine. This paper deals with the theoretical assumptions behind cluster analysis in human population genomics. Adopting an interdisciplinary approach, it demonstrates that the hypothesis that attributes the clustering of human populations to "frictional" effects of landform barriers at continental boundaries is empirically incoherent. It then contrasts the scientific status of the "cluster" and "cline" constructs in human population genomics, and shows how cluster may be instrumentally produced. It also shows how statistical values of race vindicate Darwin's argument that race is evolutionarily meaningless. Finally, the paper explains why, due to spatiotemporal parameters, evolutionary forces, and socio-cultural factors influencing population structure, continental ancestry may be pragmatically relevant to global and public health genomics. Overall, this work demonstrates that, from a biological systematic and evolutionary taxonomical perspective, human races/continental groups or clusters have no natural meaning or objective biological reality. In fact, the utility of racial categorizations in research and in clinics can be explained by spatiotemporal parameters, socio-cultural factors, and evolutionary forces affecting disease causation and treatment response.

Keywords: Darwinian classification; ancestry; cline; cluster analysis; genomic medicine; pair-wise Fst; phylogenomics; population structure.

Figure 1

(A) The effect of sampling strategies (adopted from Handley et al. 2007) [“Heterogeneous sampling can reveal genetic clusters that are biologically meaningless. The gradation in color from blue to orange represents a hypothetical situation of strictly continuous variation in allele frequencies. If sampling is heterogeneous (population samples represented here by circles) then the pattern of clinal variation can be mistaken for genetically distinct clusters (black ellipses)”] (Handley et al., 2007). (B) Global genetic diversity in humans are distributed in gradients among and within continents, emphasizes intercontinental variation. The inset figure of Africa highlights finer gradations over shorter geographic spans, emphasizing the “clinality” of human genetic variation (adopted from Cavalli-Sforza et al., 1994). Figure reproduced with permission from Cell Press/Elsevier.

Figure 2

Human metapopulations based on their divergence time estimates and evolutionary relationships (adopted from Zhivotovsky et al., , Figure 5). Zhivotovsky et al. (2003)'s Figures 5A,B clearly indicate that human metapopulations with evolutionary implications do not correspond to continental clusters considered as the placeholders for race in human population genomics. [“Population tree based on TD estimates of divergence time. (A). Divergence among major groups. The time estimates are based on 374 STRs (three outlying STRs with tetranucleotide repeats were omitted). Arrows indicate the time (lower bounds, in ky) between adjacent nodes, assuming a generation length of 25 years. (B). Schemes of divergence within the major groups, based on the 374 STRs. Time estimates within each continental group were omitted, because they may be biased owing to possible differential gene flows from other groups”] (Zhivotovsky et al., 2003). Figure reproduced with permission from Cell Press/Elsevier.

Figure 3

Conveniently defined metapopulations that mask human evolutionary history and relationships (adopted from Zhivotovsky et al., , Figure 6). This tree is simply instrumentally produced to meet the demand of our interest in continental groups/human races and may function under some circumstances as useful problem-solving tool. However, from an evolutionary perspective, it carries no natural meaning or independent reality. [“Reduced population tree showing four separation events”] (Zhivotovsky et al., 2003). Figure reproduced with permission from Cell Press/Elsevier.