Ancient oncogenesis, infection and human evolution

Abstract The recent discovery that malignant neoplastic lesions date back nearly 2 million years ago not only highlights the antiquity of cancer in the human lineage, but also provides remarkable insight into ancestral hominin disease pathology. Using these Early Pleistocene examples as a point of departure, we emphasize the prominent role of viral and bacterial pathogens in oncogenesis and evaluate the impact of pathogens on human evolutionary processes in Africa. In the Shakespearean vernacular “what's past is prologue,” we highlight the significance of novel information derived from ancient pathogenic DNA. In particular, and given the temporal depth of human occupation in sub‐Saharan Africa, it is emphasized that the region is ideally positioned to play a strategic role in the discovery of ancient pathogenic drivers of not only human mortality, but also human evolution. Ancient African pathogen genome data can provide novel revelations concerning human‐pathogen coevolutionary processes, and such knowledge is essential for forecasting the ways in which emerging zoonotic and increasingly transmissible diseases might influence human demography and longevity in the future.

The analyses of phylogenetic relationships of extant pathogens furthermore suggest that many diseases have been coevolving with humans for millennia. In addition to the classic parasite-host coevolutionary contest typified by the link between the malaria-causing Plasmodium falciparum parasite and the origin of HbS sickle-cell disease at c. 100,000 years ago (ka) (Kwiatkowski, 2005), the antiquity of genetic disease prevention mechanisms, such as the origin of immuneregulating Sia-recognizing Ig-like lectin (SIGLEC) genes before 70 ka (Wang et al., 2012), confirms that pathogens played an essential role in human evolution in Africa. Additional examples confirming longstanding exposure to pathogens include the incidence of Helicobacter pylori amongst human populations for >60,000 years (Moodley et al., 2012), evidence for the coevolution of Mycobacterium tuberculosis and humans from 70 ka (Comas et al., 2013) and recent indications that human papillomavirus (HPV) coevolved with ancestral Africans from at least c. 500 ka (Pimenoff et al., 2016). As infectious agents are recognized as selective agents for human polymorphisms, strong selection by pathogens (i.e., interactions of infectious agents with the innate immune system) is expected to be implicated in the evolution of our species (Wang et al., 2012). Pathogens (e.g., H. pylori), and also human parasites (i.e., human lice) have furthermore been used to track human population movements and have provided valuable evidence regarding human migrations within and out of Africa (Comas et al., 2013;Moodley et al., 2012;Reed, Smith, Hammond, Rogers, & Clayton, 2004) and into the New World (Raoult et al., 2008). But exactly which disease vectors and pathogens were brought from Africa to the rest of the world following the departure of behaviourally modern Homo sapiens (BMHs) from the continent after c. 100 ka (Reyes-Centeno, Hubbe, Hanihara, Stringer, & Harvati, 2015), remains unclear. While small, itinerant prehistoric foraging groups could not sustain a broad range of epidemic infectious agents (e.g., measles and influenza), it is nevertheless from this pre-65 ka sub-Saharan African "Pleistocene disease baseline" that most modern diseases derive. Indeed, current evidence suggests that at least 20 modern human diseases have certain to probable African origin, including hepatitis B, measles, HIV, Kaposi's sarcoma-associated herpesvirus (KSHV), HPV, cholera, dengue fever, sleeping sickness, P. falciparum and Plasmodium vivax malarias, leishmaniasis, plague and smallpox (Harkins & Stone, 2015;Houldcroft & Underdown, 2016;Trueba & Dunthorn, 2012;Wolfe, Dunavan, & Diamond, 2007). Many of these had a profound influence on human evolutionary history, and most of the above are still implicated in the deaths of millions of people annually.
Although recent assessments of prehistoric pathogen prevalence are providing increasingly informed perspectives on the taxonomic variety and geographic origins of diseases (Harkins & Stone, 2015), these derive largely from European and Near-Eastern Mediaeval and Holocene contexts. The analysis of ancient pathogenic DNA (apDNA) from prehistoric African contexts is lacking. As the region forms the focus of early modern human evolutionary research, one would expect the subcontinent to play a prominent role in aDNA research. African human and pathogenic aDNA is, after all, crucial to the reconstruction of the evolutionary history of anatomically modern humans (Slatkin & Racimo, 2016). While this has not yet materialized, and although the field is dominated by a few well-funded and highly specialized European laboratories, the role of sub-Saharan Africa in both a prehistoric and current global epidemiological context cannot be underestimated. Specifically, and given the temporal depth of human occupation in southern Africa, and its vast ecological and geographic diversity, the region is ideally positioned to play a strategic role in the exploration and discovery of past pathogenic drivers of human mortality. Accordingly, we present an up-to-date overview of research concerning prehistoric oncogenesis, highlighting the importance of ancient human evolutionary perspectives using aDNA to better understand modern oncogenic pathogen diversity and dynamics. We also explore the widely held misconception that pathogen-driven oncogenesis was rare or nonexistent in human prehistory, and emphasize the essential role of sub-Saharan African archaeological contexts in elucidating the evolutionary impact of oncogenic and other bacterial and viral pathogens on the evolution of our species in Africa.

| ANCIENT HUMAN HEALTH AND ONCOGENESIS
Epidemiologic transition models generally associate the emergence of most human diseases with changing living conditions resulting from agricultural innovations and higher population densities that occurred during the Neolithic Period, c. 12 ka (Omran, 1971). Consequently, the search for the origins of diseases has focussed largely on domestic animals and environments outside Africa. Many of these tropical infections are, however, likely to have played a significant role in the human evolutionary process for much lengthier periods of time (Barrett, Kuzawa, McDade, & Armelagos, 1998). It is conceivable that the original state of human disease exposure is characterized by the prehistoric sub-Saharan African populations who inhabited the region over the past 150,000 years. The potential impact of disease on prehistoric humans is illustrated by the fact that ~60% of contemporary hunter-gatherers succumb to disease before reaching reproductive age (c. 15 years) (Gurven & Kaplan, 2007). But, as indicated by the seminal review by Wolfe et al. (2007), and more recently those by Harkins and Stone (2015), Houldcroft and Underdown (2016) and Trueba and Dunthorn (2012), there are substantial discontinuities in our understanding of the origins of diseases and their influence on human evolution in Africa.
The current global disease burden is dominated by both ancestral (Houldcroft & Underdown, 2016;Wolfe et al., 2007) and novel emerging or re-emerging infectious diseases (Langwig et al., 2015;Plummer et al., 2016). Of the ~2,100 species of pathogens that affect humans (Wardeh, Risley, McIntyre, Setzkorn, & Baylis, 2015), 65% are zoonotic (Lloyd-Smith et al., 2009) and 177 (8.4%) cause emerging infectious diseases (Dutour, 2013). Of all the illnesses afflicting modern human society, cancer arguably represents one of the most enigmatical ailments (Boyle & Levin, 2008;Hanahan & Weinberg, 2000). In 2015, noncommunicable neoplasms (new and abnormal tissue growths characteristic of cancer) were a leading cause of the global disease burden (Kassebaum et al., 2016). Disability-adjusted life-years indices indicate that neoplasms were implicated in ~215 million years of life lost due to either death or disability. Neoplastic diseases were surpassed in impact only by cardiovascular and other infectious diseases. But are neoplastic diseases restricted to postindustrial human society, or can we trace the origins of malignant cancerous tumours further back in time, perhaps even into prehistory?
Citing the rarity of hominin fossil evidence for oncogenic tumours, David and Zimmerman (2010) recently concluded that cancer is a contemporary human phenomenon that is caused by the stresses of our modern lifestyle. Changes in diet and anthropogenic environmental modification are proposed to have subjected humans to toxins that contribute to cancers. Consequently, a widely held and highly erroneous perception is that the increase in and risk of contracting cancer is driven almost exclusively by anthropogenic, environmental and, to a lesser extent, inheritable (genetic) factors. But referring to a lack of evidence for the occurrence of cancer in the hominin archaeological record as indicative of the paucity of malignancies in antiquity is erroneous. Nearly all palaeopathological examples of cancer only dates to the past 500 years of human history, and evidence for cancer before the modern era is indeed rare (Binder, Roberts, Spencer, Antoine, & Cartwright, 2014). Early confirmation of neoplastic disease is however indicated by a lesion on an archaic Homo mandible from Kanam, Kenya (Phelan et al., 2007), and a fibrous dysplasia on a Neanderthal rib dated to 120 ka from the site of Krapina, Croatia (Monge et al., 2013). The recent discovery of neoplastic tumours in members of Australopithecus and early Homo (Odes et al., 2016;Randolph-Quinney et al., 2016) dated to 1.98 and c. 1.7 million years ago, respectively, provides additional insight into the antiquity of human cancers. These two remarkable Early Pleistocene South African finds also necessitate a revision of current perceptions regarding the causative factors implicated in oncogenesis.
Admittedly, individuals who succumb to death shortly after oncogenesis will not display skeletal indications of either benign or malignant cancer tumours (i.e., osteosarcoma, chondrosarcoma and multiple myeloma), while those that did survive long after the formation of tumours might, in some instances, have developed skeletal lesions (Brothwell, 2016). In addition, extraskeletal tumours leave ab-  Figure 1). Thus, and on account of this "osteological paradox" (Wood et al., 1992), disease incidence is often unnoticed or misconstrued, which leads to unverified statements that some diseases were either rare or nonexistent in prehistory.

| INTRINSIC AND EXTRINSIC FACTORS IMPLICATED IN ONCOGENESIS
The relative contribution of intrinsic (inheritable genetic) and extrinsic (environmental) risk factors in cancer development has been the subject of extensive scientific discussion (Lin et al., 2015;Luzzatto & Pandolfi, 2015;Ngeow & Eng, 2016;Pimenoff et al., 2016;Plummer et al., 2016;Tomasetti & Vogelstein, 2015;Wu, Lu, Zhou, Chen, & Xu, 2016;Wu, Powers, Zhu, & Hannun, 2016). Carcinogenesis or oncogenesis entails the process whereby normal cells are transformed into cancer cells. The progression is characterized by changes at the cellular, genetic and epigenetic levels and abnormal cell division which, in some cancers, can result in the formation of a malignant tumorous mass. Cancer cells typically acquire the ability to reproduce uncontrollably, thus resulting in the development of tumours. The underlying causative factors implicated in normal cell alterations are however highly variable, and many types of cancers arise from chronic wounds and at sites of infection and inflammation (Coussens & Werb, 2002). Tomasetti and Vogelstein (2015) recently suggested that the risk of developing cancer is strongly correlated with the total number of divisions of stem cells in specific organs or tissues. Random mutations arising during DNA replication in noncancerous stem cells are cited as a primary cause of oncogenesis. Accordingly, patients with familial adenomatous polyposis syndrome are estimated to be ~30 times more likely to develop colorectal cancer than duodenal cancer, primarily because there are ~150 times as many stem cell divisions in the colon as in the duodenum. These and other mutational errors therefore F I G U R E 1 Chronological incidence of prehistoric oncogenic tumours and important milestones concerning cancer aetiology and treatment (Binder et al., 2014;Bona et al., 2014;Monge et al., 2013;Odes et al., 2016;Phelan et al., 2007;Randolph-Quinney et al., 2016) ('Rom.' and 'Med.' referes to Roman and Medieval Periods, respectively). arise by chance during stem cell division and is said to explain more cancers than do hereditary or environmental factors. Peculiarly, the underlying mechanism is ascribed to "bad luck" as imposed by the random stochastic mutation events that occur during DNA replication. Is oncogenesis simply down to "bad luck," or are there other oncogenic mechanisms at work here?
Rudolf Virchow (1821Virchow ( -1902 first proposed the irritation hypothesis of carcinogenesis, positing that cancer development entailed the alteration of normal human cells. Following his observation of the inflammatory reaction in Schistosoma-related bladder cancers, he suggested that chronic irritation triggered the development of malignant (cancer) cells (Balkwill & Mantovani, 2001). Accordingly, the inflammatory process is characterized by damage caused by the host immune response to the infection, rather than by the infecting organism itself.
More than a century after Virchow's findings, the "chronic irritation hypothesis" remains a widely supported mechanism for carcinogenesis by infectious agents. Genetic variations also influence the likelihood of developing a particular type of cancer. Inheritable mutations or cancerpredisposing genes that increase the risk of cancer may be passed on from parent to child. While these genetic changes may well contribute to the development of cancer, they do not directly cause it. An estimated 5%-10% of all cancers are heritable, meaning that a single gene mutation contributes to the development of cancer (Ngeow & Eng, 2016). For breast cancer, a leading cause of cancer-related death in women, the most important genes implicated are BRCA1 and BRCA2.
These mutations are however only responsible for 10%-20% of cancer cases in patients with early-onset or a family history of breast cancer (Lin et al., 2015). Mutations in the TP53 gene are one of the most frequent genetic alterations in human cancers (Olivier, Hollstein, & Hainaut, 2010). TP53 is a tumour suppressor and occurs at rates ranging from 38% to 50% in oesophageal, ovarian, colorectal, lung and larynx cancers to ~5% in primary leukaemia, sarcoma, testicular cancer, malignant melanoma and cervical cancer. Long-term exposure to environmental carcinogens, including tobacco smoke, UVR exposure, vinyl chloride and herbal compounds derived from some species of plants (e.g., Aristolochia) comprise four well-documented examples of associations between an aetiologic agent and the TP53 tumour mutation.
The fact that cancer incidence varies significantly amongst populations, organs and tissue types renders the prognostic accuracy of most (but not all) risk prediction models inadequate (Wang et al., 2015). Most of these cannot completely elucidate tumour occurrence by known potential determinants, such as environmental exposure, pathogens or inherited genes . Luzzatto and Pandolfi (2015) recently highlighted the combined influence of stem cell turnover rates, stochastic mutation and exposure to known environmental mutagens in the development of cancer. Oncogenesis is dependent on various interacting and often anonymous variables, including age, sex, ethnic origin, geographic location, inheritance of susceptibility genes, obesity status, exposure to carcinogens, lifestyle idiosyncrasies and hormonal status, to pinpoint accurately, signifying inconstant and multifaceted mechanisms for cancer aetiologies.
In summary, current evidence indicates that intrinsic risk factors contribute only modestly (<10%-30%) to the lifetime risk of cancer development. On the contrary, the majority of cancers (70%-90%) can be ascribed to extrinsic environmental factors. Examples of environmentally induced cancers comprise colorectal cancer, with an estimated 75% of risk attributable to diet, malignant melanoma with 65%-86% of risk ascribed to excessive exposure to the sun and oesophageal cancers, in which case 75% are initiated by tobacco and alcohol abuse (Wu, Lu, et al., 2016;Wu, Powers, et al., 2016). This, along with several up-to-date reports (Lin et al., 2015;Ngeow & Eng, 2016;Plummer et al., 2016;Wu, Powers, et al., 2016), provides direct evidence that environmental factors can, and frequently do, play an essential role in cancer incidence. But what exactly is implied by "extrinsic environmental" factors?
In addition to >110 environmental substances known to be highly carcinogenic to humans, the International Agency for Research on Cancer (http://www.iarc.fr/) classifies ~370 chemical compounds and microorganisms as "probably carcinogenic" to humans. Although the influence of infectious organisms on carcinogenesis requires con- And as infectious organisms not currently regarded as oncogenic may play a significant role in carcinogenesis (Jacqueline et al., 2017), it must be envisaged that the incidence of cancer in prehistory is also greatly underestimated.

| PREHISTORIC HUMAN INTERACTION AND VIRAL ONCOGENESIS
If the general assumption that human cancers are caused primarily by lifestyle and environmental factors is accepted, how does one explain the incidence of cancer in preindustrialized societies? While increasing exposure to anthropogenic chemical carcinogens and dietary changes certainly does influence cancer aetiology, extrinsic environmental factors, in particular viral, bacterial and parasitic oncogenic pathogens, appears to play a primary role in cancer development. That oncogenesis has been in existence in the hominin lineage for at least 2 million years (Odes et al., 2016;Randolph-Quinney et al., 2016)   .
More than 30 bacterial, viral and parasitic pathogens are implicated directly in oncogenesis, many of which are transmitted via sexual intercourse (Kassebaum et al., 2016;Plummer et al., 2016). Arriving in Eurasia years before BMHs, Homo erectus diverged genetically and phenotypically from our last common African ancestor.
As groups of BMHs emerged from Africa after c. 65 ka, they overlapped spatially and temporally with these divergent groups. Whereas   (Houldcroft & Underdown, 2016). However, as a result of the fact that an integrated "One Health" approach, emphasizing the interconnectedness of human, animal and environmental health (Degeling et al., 2015;Gibbs, 2014), has not been applied to prehistoric human populations, current disease prevalence models provide inadequate information concerning the diseases that infected our sub-Saharan African ancestors. Given the long evolutionary association between humans and pathogens in sub-Saharan Africa, the systematic

| THE ROLE OF SOUTHERN AFRICA IN PALAEOPATHOGENIC RESEARCH
The application of state-of-the-art molecular analytical techniques to archaeological remains has transformed hominin evolutionary research. Examples of developments in the field of aDNA includes the recovery (from permafrost conditions) of aDNA from equid remains dated to ~700 ka (Orlando et al., 2013), the sequencing of the oldest human nuclear DNA (nDNA) from Sima de los Huesos (Spain) dated to 430 ka  and the oldest-known H. sapiens genome which was extracted from a human femur recovered from the banks of the Irtysh River in Siberia, dated to 45 ka . Molecular analytical techniques have also been applied to the emerging field of apDNA and have contributed significantly to understandings of historical epidemiological aetiology (Bos et al., 2015;Devault et al., 2014;Harkins & Stone, 2015;Rasmussen et al., 2015;Schuenemann et al., 2013). As an example, and given the ambiguity regarding the assignation of, for instance, M. tuberculosis or Brucella melitensis as causative agents of macromorphological skeletal features, the biomolecular (DNA) analysis of archaeological human remains has gained increasing recognition (Kay et al., 2014). Biomolecular techniques are not limited to the extraction of aDNA from skeletal remains  and have also been applied to the analyses of archaeological sediments (Haouchar et al., 2014), human and animal coprolites (Cano et al., 2014) and curated museum specimens (Yeates & Gillings, 2016).
Southern Africa is perfectly positioned to play an essential role in current palaeopathogenic research. The region boasts an unrivalled techno-cultural archaeological record spanning >2 million years and comprising >250 excavated and securely dated Late Pleistocene (125-12 ka) and Holocene (<12 ka) archaeological assemblages (Lombard et al., 2012). It is also here that, more than 32 years ago, the field of aDNA was launched with the publication of mitochondrial DNA (mtDNA) sequences derived from an extinct quagga (Equus quagga; Higuchi, Bowman, Freiberger, Ryder, & Wilson, 1984). This was followed, in 1985, by a report of the detection of human DNA in an extract of muscle from a pre-Dynastic (2,430 years) Egyptian mummy (Pääbo, 1985),  (Dutour, 2008). Accordingly, and unless detected with innovative archaeometric techniques such as X-ray synchrotron microtomography (Odes et al., 2016;Randolph-Quinney et al., 2016) or molecular (DNA) analyses, evidence symptomatic of ancient disease incidence is essentially imperceptible. Microorganisms also differ in the propensity of their DNA to decay and undergo physicochemical changes over time. nDNA degrades roughly twice as fast as mtDNA (Allentoft et al.,2012). Mycobacteria have highly resistant hydrophobic cell walls and DNA rich in guanine and cytosine. This confers greater molecular stability and allows these bacteria to physically persist for at least 250 years (Donoghue & Spigelman, 2006). Similarly, gram-negative bacteria such as Y. pestis are characterized by cell envelopes comprising a peptidoglycan cell wall between an inner and outer cell membrane (Rasmussen et al., 2015), rendering these bacteria structurally robust. Conversely, T. pallidum, the causative agent of syphilis, is a spirochaete which is prone to structural deterioration.
It is consequently not surprising that M. tuberculosis, M. leprae and Y. pestis are the subjects of the majority of ancient microbial pathogen studies. While the DNA of most bacteria and fungi are likely to be detected, viral DNA is less likely to be preserved and therefore detected (Houldcroft et al., 2017). Unlike the double-stranded DNA of bacteria, viral genetic information is encoded in a variety of structures,

Disease (agent, transmission, reservoir) Location(s) Cases Deaths Fatality (%)
Guillain-Barré syndrome (undiagnosed) Panama 1 0 0 including double-or single-stranded DNA or RNA genomes. Viral aDNA is more likely to be preserved than viral aRNA because DNA degrades more slowly than RNA, except when integrated in the host genome (Arbuckle et al., 2010). Ancient single-stranded or RNA genome viruses in archaeological samples may occur when preservation conditions are exceptional, for example in caves with cool and constant temperatures (Meyer et al., 2014) or where soft tissue has been preserved (Maixner et al., 2016).
But what are the implications of information concerning prehistoric pathogens for modern disease prevention and treatment strategies? spire are however very difficult to determine as they occur over both the long and the short term (Didelot, Walker, Peto, Crook, & Wilson, 2016). Moreover, both recombination and mutation rates vary substantially amongst pathogens (Warinner et al., 2017). While these mechanisms are important drivers of microbial genetic diversity, they complicate efforts to define species and to trace the evolutionary history of microbial lineages. Some studies have nevertheless addressed the age of bacterial pathogens that infected ancient humans, and many of these have provided significant insights into pathogen evolution. Comparative genomics can reconstruct short-term evolutionary histories of pathogen clades whose diversity converges towards a most recent common ancestor (MRCA) that existed decades, centuries or even millennia ago (Achtman, 2016;Der Sarkissian et al., 2015). For example, following calibration of the evolutionary divergence within H. pylori against ancient human migrations, the MRCA of H. pylori approximates that of anatomically modern humans. The genetic diversity of H. pylori also reflects other human demographic events, including the peopling of the Americas and Asia (Nell et al., 2013). While the MRCAs of bacterial pathogens such as M. tuberculosis and Y. pestis span some 6,000 years, comparative genomics of modern isolates suggests that these bacteria also spread across the globe following human dispersals from Africa during the Pleistocene. The characterization of historical Y. pestis strains and their comparison to extant strains provide insight into the role of bacterial evolution in epidemiological virulence and communicability (Rasmussen et al., 2015). Genomics has also enabled the use of entire pathogen genomes to search for protective antigens that were impossible to identify with conventional technologies. Following the successful development of a vaccine against smallpox (V. major) by Edward Jenner in 1796 (Funkhouser, 2010) were instead administered to younger persons, who benefitted most.

| CONCLUSION
It is evident that ancient biomolecular research can contribute to existing genome databases which may have public health benefits by providing tools for developing therapeutics, particularly if virulent forms of ancient diseases re-emerge. This is important as history has taught us that disease is by far the most effective eradicator of our species. Past pandemics are much more than just ancient history. They are important drivers of human genetic diversity and natural selection (Pittman, Glover, Wang, & Kol, 2016). It is also clear that the long-term tracing of genetic adaptations and rates of evolutionary change are highly informative in understanding how a pathogen becomes virulent or transmissible, providing insights into how we can effectively manage future epidemics (Andam, Worby, Chang, & Campana, 2016;Boire et al., 2014).
DNA preservation is widely cited as a primary limiting factor pertaining to aDNA from tropical and subtropical African contexts, and most studies are based on finds from Northern Hemisphere and predominantly permafrost contexts (Haile et al., 2009;Kistler, Ware, Smith, Collins, & Allaby, 2017). Temperate and Arctic regions have generally yielded more aDNA sequences than tropical regions, partly because conditions are more favourable to the preservation of aDNA, but also because they have been sampled more intensively (Slatkin & Racimo, 2016). However, the recovery of human nuclear aDNA from Sima de los Huesos  and human mtDNA from Mota Cave in Ethiopia (at 4.5 ka) (Llorente et al., 2015(Llorente et al., , 2016 and St. Helena Cave, South Africa (at 2.3 ka) (Morris, Heinze, Chan, Smith, & Hayes, 2014) suggests that chronological age does not predict DNA fragmentation and that aDNA and apDNA preservation is not contingent exclusively on subzero temperatures (Kistler et al., 2017). The prospect of retrieving both human and apDNA from sub-Saharan African contexts is increasingly promising.
The past provides a prologue for discussions regarding emerging diseases, whether it concerns the biological origins of a potential pandemic or its social repercussions (Heymann, 2007). Disease epidemics are not new and they will continue to affect and potentially devastate human populations. Significantly, the exclusive focus on diseases that have emerged within the past decades is cited as responsible for the lack the temporal depth necessary to examine the changes in the behaviour of emerging diseases and the long-term interactions between pathogens and human hosts (DeWitte, 2016).
The severe economic and social repercussions of disease epidemics are clearly demonstrated by historical (e.g., plague, smallpox and influenza) and current (i.e., Zika, Ebola and SARS) examples. But the biological origin of a many prehistoric, historical and even contemporary causative pathogens remains mysterious. The emphasis should therefore also be on the development of sub-Saharan capabilities to detect, predict, prevent and control all potential infectious disease epidemics rather than waiting for known diseases to threaten global human health. This is particularly important given the current global interconnectedness, which can put people at risk of diseases that emerge in distant locales. In addition, the discovery and re-animation of two 30,000-year-old viruses (Pithovirus sibericum and Mollivirus sibericum) from Siberian permafrost (Legendre et al., 2015) highlights the severity of the impact that an increasingly warmer globe might have on pathogen prevalence (Wu, Lu, et al., 2016). Warmer temperatures and increased rainfall readily facilitate the introduction of new species of plants, animals and also microorganisms, altering the composition and dominance patterns of existing communities and increasing the susceptibility of humans to re-emerging and even novel pathogens (Pauchard et al., 2015). Current climate models consistently predict increasingly suitable climatic conditions for endemic malaria transmission in Central Europe and North America (Caminade et al., 2014), and even in Northern Europe, pathogenic bacteria such as Vibrio cholerae (Baker-Austin, Trinanes, Gonzalez-Escalona, & Martinez-Urtaza, 2017) are becoming increasingly prevalent. In the Southern Hemisphere and in sub-Saharan Africa in particular, there is a direct correlation between increasing rainfall, warmer temperatures and the prevalence of infectious and also vector-borne diseases, including malaria, trypanosomiasis, schistosomiasis, chikungunya and plague (Rosenthal, Ostfeld, McGarvey, Luriea, & Smith, 2015;Stensgaard, Booth, Nikulin, & McCreesh, 2015). This realization corroborates the significance of information derived from palaeopathogenic research on sub-Saharan African archaeological contexts.
Because of the paucity of aDNA sequences from Africa, these novel pathogen genomes will be highly valuable and decidedly revealing, providing novel revelations concerning human-pathogen coevolutionary processes (Slatkin & Racimo, 2016). The unique combination of an unrivalled archaeological record and a thriving and highly skilled academic community therefore places southern African archaeologists, geneticists and medical scientists in a prime position to explore past pathogenic influences and to contribute to the improvement of human health and longevity.