Adaptation to infectious disease exposure in indigenous Southern African populations

Abstract

Genetic analyses can provide information about human evolutionary history that cannot always be gleaned from other sources. We evaluated evidence of selective pressure due to introduced infectious diseases in the genomes of two indigenous southern African San groups-the ‡Khomani who had abundant contact with other people migrating into the region and the more isolated Ju|'hoansi. We used a dual approach to test for increased selection on immune genes compared with the rest of the genome in these groups. First, we calculated summary values of statistics that measure genomic signatures of adaptation to contrast selection signatures in immune genes and all genes. Second, we located regions of the genome with extreme values of three selection statistics and examined these regions for enrichment of immune genes. We found stronger and more abundant signals of selection in immune genes in the ‡Khomani than in the Ju|'hoansi. We confirm this finding within each population to avoid effects of different demographic histories of the two populations. We identified eight immune genes that have potentially been targets of strong selection in the ‡Khomani, whereas in the Ju|'hoansi, no immune genes were found in the genomic regions with the strongest signals of selection. We suggest that the more abundant signatures of selection at immune genes in the ‡Khomani could be explained by their more frequent contact with immigrant groups, which likely led to increased exposure and adaptation to introduced infectious diseases.

Human Immunology through the Lens of Evolutionary Genetics

“…Another study explored adaptation to infectious diseases in two African San groups of hunter-gatherers: the zKhomani, who have had extensive contact with incoming farmers and herders, and the more isolated Juj'hoansi (Owers et al, 2017). Interestingly, immune genes showed strong signals of selection in the zKhomani but not in the Juj'hoansi, suggesting that the adaptation of immune functions can be rapidly triggered by contact with external groups importing new pathogens (Figure 3).…”

Population isolation predicts the severity of historical human epidemics

“…Conversely, island populations are known to have population genetic structure (Friedlaender et al, ), suggesting that these populations were sufficiently isolated to allow meaningful population differentiation. This is particularly notable given that historical smallpox epidemics have previously been shown to cause population‐level genomic differences consistent with selection favouring individuals with increased resistance (Owers et al, ). Although not conclusive, the decline in mortality in subsequent epidemics and the increased severity of epidemics among indigenous groups are also consistent with long‐term population‐level changes driving epidemic severity (Figure ).…”

“…Both smallpox and influenza are pathogens that arose in the Old World and were largely restricted to those areas until the European colonial period (Porras‐Gallo & Davis, ). In particular, the spread of smallpox is particularly well documented (Owers et al, ; Porras‐Gallo & Davis, ), largely owing to its historical importance, its relatively easy identification and its deadly consequences. The well‐described spread of smallpox allows a high level of confidence when identifying an epidemic as first contact.…”

“…Crucially, these first‐contact epidemics (also referred to as virgin soil epidemics) are typically limited largely to indigenous groups, even where colonizing Eurasian populations co‐occur (Denevan, ). This suggests that long‐term changes to populations might underlie the tremendous severity of such epidemics (Karlsson, Kwiatkowski, & Sabeti, ; Owers, Sjödin, Skoglund, Soodyall, & Jakobsson, ) and that geographical isolation might cause temporal isolation from human pathogens. Given that temporal isolation from a disease is likely to be most proximately responsible for mediating epidemic severity, we may also predict that subsequent epidemics of the same disease in the same population would be less severe (Cliff et al, ).…”

“…Given that temporal isolation from a disease is likely to be most proximately responsible for mediating epidemic severity, we may also predict that subsequent epidemics of the same disease in the same population would be less severe (Cliff et al, ). Despite the importance of isolation for understanding epidemic severity, to our knowledge no study has attempted to link such ecological concepts to historical human epidemics over long time‐scales (but see Owers et al, , for the effects of isolation on disease and human population genetics).…”