Professor Simon Underdown

We investigate the bacterial and fungal composition and functionality of the Ju|’hoansi intestinal microbiome (IM). The Juǀʼhoansi are a hunter-gatherer community residing in northeastern Namibia. They formerly subsisted by hunting and gathering but have been increasingly exposed to industrial dietary sources, medicines, and lifestyle features. They present an opportunity to study the evolution of the human IM in situ, from a predominantly hunter-gatherer to an increasingly Western urban-forager-farmer lifestyle. Their bacterial IM resembles that of typical hunter-gatherers, being enriched for genera such as Prevotella, Blautia, Faecalibacterium, Succinivibrio, and Treponema. Fungal IM inhabitants include animal pathogens and plant saprotrophs such as Fusarium, Issatchenkia, and Panellus. Our results suggest that diet and culture exert a greater influence on Ju|’hoansi IM composition than age, self-identified biological sex, and medical history. The Ju|’hoansi exhibit a unique core IM composition that diverges from the core IMs of other populations.

The impact of endemic and epidemic disease on humans has traditionally been seen as a comparatively recent historical phenomenon associated with the Neolithisation of human groups, an increase in population size led by sedentarism, and increasing contact with domesticated animals as well as species occupying opportunistic symbiotic and ectosymbiotic relationships with humans. The orthodox approach is that Neolithisation created the conditions for increasing population size able to support a reservoir of infectious disease sufficient to act as selective pressure. This orthodoxy is the result of an overly simplistic reliance on skeletal data assuming that no skeletal lesions equated to a healthy individual, underpinned by the assumption that hunter-gatherer groups were inherently healthy while agricultural groups acted as infectious disease reservoirs. The work of Van Blerkom (2003), Wolfe et al (2007) and Houldcroft & Underdown (2016) has changed this landscape by arguing that humans and pathogens have long been fellow travellers. The package of infectious diseases experienced by our ancient ancestors may not be as dissimilar to modern infectious diseases as was once believed. The importance of DNA, from ancient and modern sources, to the study of the antiquity of infectious disease, and its role as a selective pressure cannot be overstated. Here we consider evidence of ancient epidemic and endemic infectious diseases with inferences from modern and ancient human and hominin DNA, and from circulating and extinct pathogen genomes. We argue that the pandemics of the past are a vital tool to unlock the weapons needed to fight pandemics of the future.

Changing climatic conditions are thought to be a major control of human presence in Arabia during the Paleolithic. Whilst the Pleistocene archaeological record shows that periods of increased monsoon rainfall attracted human occupation and led to increased population densities, the impact of arid conditions on human populations in Arabia remains largely speculative. Here, we present data from Jebel Faya in Southeast (SE) Arabia, which document four periods of human occupation between c. 210,000 and 120,000 years ago. The Jebel Faya record indicates that human occupation of SE Arabia was more regular and not exclusively linked to major humid periods. Our data show that brief phases of increased rainfall additionally enabled human settlement in the Faya region. These results imply that the mosaic environments in SE Arabia have likely formed a population refugia at the end of the Middle and the beginning of the Late Pleistocene. 

Background
The archaeological incidence of ancient human faecal material provides a rare opportunity to explore the taxonomic composition and metabolic capacity of the ancestral human intestinal microbiome (IM). Here, we report the results of the shotgun metagenomic analyses of an ancient South African palaeo-faecal specimen.

Methods
Following the recovery of a single desiccated palaeo-faecal specimen from Bushman Rock Shelter in Limpopo Province, South Africa, we applied a multi-proxy analytical protocol to the sample. The extraction of ancient DNA from the specimen and its subsequent shotgun metagenomic sequencing facilitated the taxonomic and metabolic characterisation of this ancient human IM.

Results
Our results indicate that the distal IM of the Neolithic ‘Middle Iron Age’ (c. AD 1460) Bantu-speaking individual exhibits features indicative of a largely mixed forager-agro-pastoralist diet. Subsequent comparison with the IMs of the Tyrolean Iceman (Ötzi) and contemporary Hadza hunter-gatherers, Malawian agro-pastoralists and Italians reveals that this IM precedes recent adaptation to ‘Western’ diets, including the consumption of coffee, tea, chocolate, citrus and soy, and the use of antibiotics, analgesics and also exposure to various toxic environmental pollutants.

Conclusions
Our analyses reveal some of the causes and means by which current human IMs are likely to have responded to recent dietary changes, prescription medications and environmental pollutants, providing rare insight into human IM evolution following the advent of the Neolithic c. 12,000 years ago.

Background. Simoni et al (2016) reported variation in the frequency of Neanderthal alleles found in modern humans and argued that they may have provided an evolutionary advantage. One such allele is SNP rs3917862, associated with hypercoagulability. rs3917862 can be deleterious but can also help prevent blood loss. We investigated two possible selective pressure hypotheses for rs3917862 surviving to higher frequencies: deaths from interpersonal violent trauma and childbirth. Results. Mortality data from modern hunter-gatherers models the living conditions and causes of death of humans and Neanderthals at the point of admixture. National census data indicates a positive correlation between presence of rs3917862 and decreased maternal mortality ratios. When maternal mortality ratio is modelled using GDP, births attended by skilled assistants and the presence of rs3917862, women are 0.1% more likely to die in childbirth in populations lacking rs3917862. Deaths due to violence show no correlation with rs3917862. Conclusion. These findings challenge the idea that Neanderthal admixture has negatively impacted the overall health of modern humans. Maternal survival may have acted as a selective pressure for the persistence of hypercoagulability alleles in modern Europeans. Understanding the role of hypercoagulability in childbirth, and the role of rs3917862, could help to reduce maternal mortality ratios.

High quality Altai Neanderthal and Denisovan genomes are revealing which regions of archaic hominin DNA have persisted in the modern human genome. A number of these regions are associated with response to infection and immunity, with a suggestion that derived Neanderthal alleles found in modern Europeans and East Asians may be associated with autoimmunity.  As such Neanderthal genomes are an independent line of evidence of which infectious diseases Neanderthals were genetically adapted to. Sympathetically, human genome adaptive introgression is an independent line of evidence of which infectious diseases were important for AMH coming in to Eurasia and interacting with Neanderthals. The Neanderthals and Denisovans present interesting cases of hominin hunter-gatherers adapted to a Eurasian rather than African infectious disease package. Independent sources of DNA-based evidence allow a re-evaluation of the first epidemiologic transition and how infectious disease affected Pleistocene hominins. By combining skeletal, archaeological and genetic evidence from modern humans and extinct Eurasian hominins we question whether the first epidemiologic transition in Eurasia featured a new package of infectious diseases, or a change in the impact of existing pathogens. Coupled with pathogen genomics, this approach supports the view that many infectious diseases are pre-Neolithic, and the list continues to expand. The transfer of pathogens between human populations, including the expansion of pathogens from Africa, may also have played a role in the extinction of the Neanderthals and offers an important mechanism to understand hominin-hominin interactions well back beyond the current limits for aDNA extraction from fossils alone.

Human-wildlife conflict, specifically crop raiding by wildlife, is an increasing concern. Primates are a particular problem across much of Africa and Asia, especially for rural, subsistence farmers living and farming at the forest edge. Most methods designed for sampling and extrapolating from primate crop damage in a subsistence farming context require extensive data collection and involve considerable expenditure of time to complete data analysis. Using a standard epidemiological model, we predict the relative risk of primate crop raiding based on crops grown, their availability within individual farms and patterns of primate selectivity. The model produces an index of relative risk of crop raiding by primates within a geographical region. It rapidly ranks farms according to their vulnerability to crop raiding, with limited need for in-depth data collection. It will therefore allow a more effective deployment of protection methods and more pro-active targeting of resources. This method of modelling primate crop damage can be taught to local communities rapidly and easily. Although not designed to replace existing methods, it can run effectively in conjunction with them.