Press release

Global map of the sickle cell gene confirms the 'malaria hypothesis'

On a global scale, the sickle-cell gene is most commonly found in areas with historically high levels of malaria, adding geographical support to the hypothesis that, while potentially deadly, the gene avoids disappearing through natural selection by providing protection against malaria.

In a study funded by the Wellcome Trust, geographers, biologists and statisticians at the University of Oxford, together with colleagues from the KEMRI-Wellcome Trust Research Programme in Kenya, have produced the first detailed global map showing the distribution of the sickle-cell gene. The results are published today with open access in the journal 'Nature Communications'.

Haemoglobin S (HbS) is known to cause sickle-cell disease, which is usually fatal if left untreated. Natural selection suggests that such a disadvantageous gene should not survive, yet it is common in people of African, Mediterranean and Indian origin.

More than 60 years ago, researchers observed that the sickle-cell gene tended to be more common in populations living in, or originating from, areas of high malaria prevalence. This led to the 'malaria hypothesis', which suggested that, although deadly when inherited from both parents, the gene provided a degree of protection from malaria in children inheriting it from just one parent. This protective advantage was strong enough in areas of intense malaria transmission for the gene to survive.

The malaria hypothesis has since been supported by both population and laboratory studies, but the original observations of a geographical overlap between frequency of the gene and malaria prevalence have never been tested beyond simple, visual comparisons at the global scale.

To address this, Dr Fred Piel and colleagues collated all the information currently accessible on the occurrence of the sickle-cell gene in native populations worldwide, and used modern mapping techniques to create a map of the global frequency of the gene. The map was then compared with the distribution and intensity of malaria before widespread malaria control.

The study showed that the sickle-cell gene is most common in sub-Saharan Africa, the Middle East and India. Areas of high frequency are coincident with historically high levels of malaria, thus confirming that the malaria hypothesis is correct at the global scale.

"This study highlights the first steps in our efforts to create an open-access, online database of the frequency of various inherited blood disorders," says lead author Dr Piel, from the University of Oxford. "Such databases will help to improve estimates of public health burdens, and act as guides on where resources would be best applied."

Co-author Dr Simon Hay adds: "The malaria hypothesis is the textbook example of a natural selection 'balancing act', where selection against an unfavourable mutation is weighed against selection in favour of a protective gene."

The sickle-cell frequency map was created as part of the activities of the Malaria Atlas Project, a multinational research collaboration funded primarily by the Wellcome Trust.


Piel F et al. Global distribution of the sickle-cell gene and geographical confirmation of the malaria hypothesis. Nat Commun 2 Nov 2010.

About the Malaria Atlas Project

The Malaria Atlas Project (MAP) is funded by the Wellcome Trust to assemble medical intelligence and survey data to provide evidence-based maps on the distribution of malaria risk, human population, disease burdens, mosquito vectors, inherited blood disorders and malaria financing and control worldwide. The maps generated are the results of a collaboration between malaria scientists in the UK, Kenya, Vietnam, Indonesia, Ecuador and the USA. MAP work in the Asia-Pacific region has been additionally supported by grants from the Li Ka Shing Foundation.

About the Department of Zoology

The Department of Zoology, within the Mathematical, Physical and Life Sciences Division at the University of Oxford, has a long-standing reputation for world-class research and teaching. Research in the department is organised into several research themes; these span a broad spectrum of biology ranging from ecology and behaviour, through to molecular evolution, development and infectious disease biology.

About the Kenya Medical Research Institute

The Kenya Medical Research Institute (KEMRI) is a Kenya government parastatal with the responsibility for research to improve the health of Kenyans. It is one of the most well developed national research institutes in Africa with a network of centres across Kenya such as the Centre of Geographic Medicine Research Coast (CGMR-C), which is home to the KEMRI-Wellcome Trust Research Programme. The Programme formally established in 1989, is a partnership between KEMRI, the University of Oxford and the Wellcome Trust. It conducts basic epidemiological and clinical research, with results feeding directly into local and international health policy, and aims to expand the country's capacity to conduct multidisciplinary research that is strong, sustainable and internationally competitive.

About The Weatherall Institute of Molecular Medicine

The Weatherall Institute of Molecular Medicine (WIMM) fosters research in molecular and cell biology with direct application to the study of human disease. Housing around four hundred scientists, WIMM is proud to be at the forefront of an exciting research field impacting on the understanding and treatment of diseases ranging from cancer to AIDS. The Institute was founded by Professor David Weatherall in 1989. The three main sponsors of research in the Institute are the University of Oxford, the Medical Research Council and Cancer Research UK. Significant funding also comes from the Wellcome Trust and other medical research charities.

About The Philippe Wiener-Maurice Anspach Foundation

The Philippe Wiener-Maurice Anspach Foundation aims to promote cultural relations between the Université Libre de Bruxelles (ULB) [Free University of Brussels] and the Universities of Oxford and Cambridge. Since 1969 it has offered awards each year to students and postdoctoral researchers from Brussels to Oxford and Cambridge, and vice versa.

About the Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.