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Adaptation to malaria in hunter-gatherers 7000 years ago

March 12, 2021 - OTAGO, New Zealand

New bioarchaeological research shows malaria has threatened human communities for more than 7000 years, earlier than when the onset of farming was thought to have sparked its devastating arrival.

Lead author Dr Melandri Vlok from the Department of Anatomy, University of Otago, says this ground-breaking research, published today in Scientific Reports, changes the entire understanding of the relationship humans have had with malaria, still one of the deadliest diseases in the world.

"Until now we've believed malaria became a global threat to humans when we turned to farming, but our research shows in at least Southeast Asia this disease was a threat to human groups well before that.

"This research providing a new cornerstone of malaria's evolution with humans is a great achievement by the entire team," Dr Vlok says.

Cranial evidence for thalassemia at Man Bac. (a) Anterior protrusion of the zygomatic bones consistent with rodent facies (MB05M3, approx. 6 months old, antero-lateral aspect). (b) and (c) Diploic expansion of the cranial vault. There is no porosity on the ectocranium but hair-on-end formations are present on the endocranium (MB05M12, approx. 2 years, lateral aspect). (d) Marrow hyperplasia of the zygomatic bones (MB05M12, antero-posterior view). (e) Lack of pneumatization of the frontal sinus (MB07H1M1, approx. 12 years, antero-posterior view). (f) Rodent facies of the maxilla, mandible and zygoma (MB07H2M26, approx. 1.5 years, antero-superior aspect). (g) Severe cribra orbitalia (white circle) and diploic expansion of the crania (black arrow, antero-lateral aspect) (MB07H1M1). (h) Marrow hyperplasia of the left zygoma (MB07H1M1, lateral aspect). (i) and (j) Marrow hyperplasia of the maxilla (MB07H1M1, superior-inferior view). The expanse of the marrow hyperplasia is indicated by the white arrows. Article authors (Creative Commons Attribution 4.0 International License).

Still a serious health issue, as recently as 2019 the World Health Organization reported an estimated 229 million cases of malaria around the world, with 67 per cent of malaria deaths in children under the age of 5 years.

While malaria is invisible in the archaeological record, the disease has changed the evolutionary history of human groups causing consequences visible in prehistoric skeletons. Certain genetic mutations can lead to the inheritance of Thalassemia, a devasting genetic disease that in its milder form provides some protection against malaria.

Deep in humanity's past, the genes for malaria became more common in Southeast Asia and the Pacific where it remains a threat, but up until now the origin of malaria has not been pinpointed. This research has identified thalassemia in an ancient hunter-gatherer archaeological site from Vietnam dated to approximately 7000 years ago, thousands of years before the transition to farming in the region.

In some parts of the world, slashing and burning in agricultural practice would have created pools of stagnant water attracting mosquitos carrying malaria, but in Southeast Asia these mosquitos are common forest dwellers exposing humans to the disease long before agriculture was adopted.

The study Forager and farmer evolutionary adaptations to malaria evidenced by 7000 years of thalassemia in Southeast Asia is a result of combined efforts from years of investigation by a team of researchers led by Professor Marc Oxenham (currently at the University of Aberdeen) and including researchers from University of Otago, the Australian National University (ANU), James Cook University, Vietnam Institute of Archaeology and Sapporo Medical University.

The research is the first of its kind to use microscopic techniques to investigate changes in bone tissue to identify thalassemia. In 2015, Professor Hallie Buckley from the University of Otago noticed changes in the bone of hunter-gatherers that made her suspicious that thalassemia might be the cause, but the bones were too poorly preserved to be certain. Professor Buckley called in microscopic bone expert Dr Justyna Miszkiewicz of ANU to investigate. Under the microscope, the ancient samples from Vietnam showed evidence for abnormal porosity mirroring modern-day bone loss complications in thalassemic patients.

At the same time, Dr Vlok, completing her doctoral research in Vietnam, found changes in the bones excavated in a 4000-year-old agricultural site in the same region as the 7000-year-old hunter-gatherer site. The combined research suggests a long history of evolutionary changes to malaria in Southeast Asia which continues today.

"A lot of pieces came together, then there was a startling moment of realisation that malaria was present and problematic for these people all those years ago, and a lot earlier than we've known about until now," Dr Vlok adds.

Vlok, M., Buckley, H. R., Miszkiewicz, J. J., Walker, M. M., Domett, K., Willis, A., … Oxenham, M. F. (2021). Forager and farmer evolutionary adaptations to malaria evidenced by 7000 years of thalassemia in Southeast Asia. Scientific Reports, 11(1). doi:10.1038/s41598-021-83978-4

Abstract: AbstractThalassemias are inherited blood disorders that are found in high prevalences in the Mediterranean, Southeast Asia and the Pacific. These diseases provide varying levels of resistance to malaria and are proposed to have emerged as an adaptive response to malaria in these regions. The transition to agriculture in the Holocene has been suggested to have influenced the selection for thalassemia in the Mediterranean as land clearance for farming encouraged interaction between Anopheles mosquitos, the vectors for malaria, and human groups. Here we document macroscopic and microscopic skeletal evidence for the presence of thalassemia in both hunter-gatherer (Con Co Ngua) and early agricultural (Man Bac) populations in northern Vietnam. Firstly, our findings demonstrate that thalassemia emerged prior to the transition to agriculture in Mainland Southeast Asia, from at least the early seventh millennium BP, contradicting a long-held assumption that agriculture was the main driver for an increase in malaria in Southeast Asia. Secondly, we describe evidence for significant malarial burden in the region during early agriculture. We argue that the introduction of farming into the region was not the initial driver of the selection for thalassemia, as it may have been in other regions of the world.

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