The findings could help explain how malaria spread throughout the human population over the past several thousand years and pinpoint the source of the variety of genetic mutations that makes P.falciparum resistant to anti-malarial drugs. The findings appear in today's issue of the journal Science.

Malaria is the world's most serious parasitic tropical disease and kills more people than any other communicable disease except for tuberculosis.

P.falciparum, the most lethal form of the disease, accounts for the majority of infections, 200 to 300 million, resulting in 1 to 3 million deaths annually.

Malaria is a curable disease if promptly diagnosed and adequately treated. Increased risk of the disease is associated with land use changes such as agricultural and irrigation projects in frontier areas such as the Amazon, Southeast Asia and Sub-Saharan Africa and by the emergence and spread of drug-resistant parasites.

The researchers examined and sequenced introns from the first completely sequenced parasite chromosomes covering wide-ranging geographic areas including Africa, Honduras, Thailand and Papua New Guinea.

The scientists are working on the Harvard-Oxford Malaria Genome Project, which uses published DNA sequence information from the Malaria Genome Project, which is sponsored by the Wellcome Trust.

They were able to estimate that the most recent common ancestor of all P.falciparum in existence dates back between 3,000 and 10,000 years, a far more recent estimate than the previously believed ancient origins.

The estimate is supported by evidence from natural history dating back less than 6,000 years ago with the advent of slash-and-burn agricultural methods in African rainforests and recently-discovered gene mutations in humans. The newly cleared sun-filled terrain, with pools and puddles of water, could have provided the ideal mosquito vector for P.falciparum.

With a sufficient human and vector populations large enough to maintain transmission of the parasite, the researchers suggest that two evolutionary courses for the single ancestor are possible: The sole ancestor of all existing P.falciparum established itself either from a single strain supplanting the others through superior strength or, less likely, by the chance coincidence to spread.

Dyann Wirth is Director of the Harvard Malaria Initiative and Professor of Immunology and Infectious Diseases in the Department of Immunology and Infectious Diseases at the Harvard School of Public Health. She said, "Our research suggests a new mechanism developed by the parasite to rapidly generate diversity in selected genes and has important implications for drug and vaccine development."

Professor Karen Day, an epidemiologist in infectious disease at Oxford University, said, "Like HIV, which is thought to have spread widely when humans started migrating throughout the African continent, the emergence of malaria as a severe threat to humans was caused by changes in human behavior; in this case, the development of agriculture. Our determination of the true age of P. falciparum has again demonstrated that nature is inherently dynamic, and as our behavior changes so too will that of our biological enemies."

The researchers also found that the lack of variation in the "neutral genes" of P. falciparum contrasts strikingly with the extraordinary diversity in genes which confer drug resistance or help the malaria parasite evade the host immune response.

This contrast will allow scientists to identify the genes that are essential to parasite survival as they continue to unravel the functions of the many genes in the malaria genome.

The research was conducted by teams at the University of Oxford led by Professor Day and at Harvard led by Professors Daniel Hartl and Dyann Wirth. The research was funded by the National Institutes of Health, the Wellcome Trust and the Burroughs-Wellcome Fund.

Harvard School of Public Health is dedicated to advancing the public's health through learning, discovery, and communication. More than 300 faculty members are engaged in teaching and training the 800-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world.

Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children's health to quality of care measurement; from health care management to international health and human rights.

The Wellcome Trust is an independent research-funding charity, established under the will of Sir Henry Wellcome in 1936. The Trust's mission is to foster and promote research with the aim of improving human and animal health.

Related websites:

The Wellcome Trust

Harvard School of Public Health

[Contact: Kevin Myron ]

20-Jul-2001