Dr Wells and the genetic crusade

A young American genetist is embarking on a project which could solve many of the mysteries of human history, and give each of us a chance to find out about our our oldest ancestors.

We liked the dictionary, and Spencer Wells and the National Geographic Society absolutely promise that we'll love the novel.

The Human Genome Project provided the first comprehensive map of the structure of the human genome, a catalogue of every gene, and the complete DNA source code for making a human being.

Wells is now heading an equally ambitious research project, the Genographic Project, sponsored by the National Geographic Society, which aims to retrace the migratory routes and evolution of modern human beings since they began dispersing from our species' African homeland around 60,000 years ago.

The human geneticist, who visited Australia last month to publicise the Genographic Project, has already sketched the story in broad detail in his 2002 book The Human Journey, and an accompanying TV documentary.

Wells described how he used Y-chromosome genetic markers to retrace the migratory routes of humans moving out of northern Africa's savannah grasslands in pursuit of a the similarly abundant herbivores grazing the vast grasslands of the central Asian steppes.

Wells identified a central way-station in latter-day Uzbekistan, in central Asia, from which physically modern humans moved westwards into Europe and eastwards into Asia, eventually reaching north-east into frigid Siberia. At the height of the last glacial period, around 15,000 years ago, they crossed the frozen Bering Strait to populate the Americas.

By around 1500 years ago, skilled Polynesian mariners in large, expeditionary canoes had reached even the most remote habitable islands of their Pacific waterworld.

The Genographic Project seeks to resolve the fine details of who begat whom, and the intricate history of cultural takeovers and mergers over the past 60,000 years.

Wells' visit to Australia was made, in part, to seek the participation of Australian Aboriginal groups. He believes that the original Australians hold the key to developing a comprehensive picture of the earliest phases of the African diaspora.

During his own journey in pursuit of the Y chromosome story in the late 1990s, Wells took blood samples from males of Dravidian ancestry in southern India. The Dravidians were among India's earliest colonists; they now live among the descendants of a later wave of Sanskrit speakers -- like Latin and ancient Greek, Sanskrit is an a branch of the Indo-European 'mother tongue', more closely related to modern English and French than to Dravidian.

Wells was looking for a genetic marker called M130, the most ancient, non-African, Y-chromosome marker. It is rare in Dravidians, but quite common in Australian Aboriginal males -- and, intriguingly, in the Na Dene peoples of the Pacific north-west of North America.

The Na Dene peoples are descended from a second, later wave of immigrants into North America, who were ultimately of Sino-Tibetan stock -- M130 is both the oldest non-African Y-chromosome marker, and the most travelled.

Wells' suspicion that M130 might have survived, at very low frequency, in southern coastal regions of India, was proven correct

The first African emigres left a durable calling card on the coastal migratory route between Africa and Australia.

The M130 story exemplifies the rich and potentially astonishing trove of stories that Wells believes reside in the genes of living and ancient human beings. Augmenting and complementing the genetic data, the similarities in living and dead languages promise to extend the human story well beyond the earliest written records from 5000 to 6000 years ago, perhaps as far back as 100,000 years.

The brilliant young Stanford-trained human geneticist is a protege of the eminent Italian molecular geneticist Prof Luigi Luca Cavilli-Sforza. In the early 1990s, Cavilli-Sforza constructed two extended family pedigrees of modern humans, one based on mitochondrial DNA, the other on language groups.

They proved to be remarkably congruent, confirming the close association between genes and languages. Like genes, languages 'mutate' in a phonetically consistent manner that allows linguists to infer deep connections between languages, and entire language groups -- linguistics data will be used to corroborate and augment the genetic data from the Genographic Project.

Cavilli-Sforza's monumental Atlas of Human Blood Groups used blood proteins, rather than genes, to reconstruct broad patterns of human migrations and infer relationships between modern cultural groups.

In 1993, he proposed an international research project to complement the nascent Human Genome Project. His Human Genome Diversity Project (HGDP) had the ambitious goal of sampling the DNA of all the world's indigenous and cultural groups.

The project succumbed to a campaign of misinformation led by the Canadian-based NGO formerly known as Rural Affairs Foundation International (RAFI), now ETC. RAFI and its supporters, claiming to represent the interests of indigenous populations and cultures, dubbed the HGDP the 'Vampire Project' and claimed it was a ruse by Western scientists to expropriate and patent unique gene alleles discovered during the project.

Wells said the Genographic Project is structured very differently. "We want indigenous people to be actively involved in deciding which questions should be asked, what analyses we should be doing, and what they want to get out of the data," he said. "Times have moved on -- in that era [the early 1990s] scientists in Jurassic Park were cloning dinosaurs from DNA preserved in amber, and people were concerned about what genetics could or couldn't do.

"We haven't received much opposition this time. Some people have asked how the project differs from the HGDP, but while some of the goals overlap, it's not the same project.

"More and more people are interested in human evolutionary history. We're being very clear about what we're doing, or not doing, and about how the data will be used."

Wells said the collected data set will be publicly available, but security systems will ensure that there is no way for researchers to identify individual participants - personal genetic data will only be accessible to its owners via password.

Wells said the project has the potential to resolve long-standing questions about the origins of modern human groups, and their genetic and linguistic relationships. And he is in no doubt that the results will be revelatory, and full of surprises.

Typical of the mysteries that might be resolved is the question of the origins of the Basques of the Spanish and French Pyrenees. The Basques form a genetic and linguistic island in a sea of modern, Indo-European-speaking Europeans. Their language has no obvious affinity to the Romance, Germanic or Slavic language groups, nor to the Finno-Ugric languages like Finnish, Lappish, Estonian or Magyar Hungarian.

There is a similar linguistic mystery 9000 kilometres away, in Pakistan's remote Hunza Valley, where people speak an ancient language called Burushaski, with no obvious affinity to the dominant Indo-European languages of the region.

Wells hopes that detailed genetic studies may support -- or refute -- an intriguing relationship, suggested by recent linguistic studies.

Some linguists now believe, on the basis of grammatical similarities, that Basque and Burushaski may be related -- tiny, living relics of an earlier 'mother tongue' spoken across Eurasia. The mysterious, now-extinct Tuscan language of pre-Roman Italy, and a pre-Indo-European language spoken in Greece, may have belonged to the same language phylum.

The origins of Australia's Aborigines is a much older and deeper mystery.

"We hope to determine when the first Australians arrived in the continent," Wells said. "It's clear that the first Australians came here from somewhere else, because there are no primates in Australia, and no way humans could have evolved de novo within Australia.

"There are two very divergent language families -- one around the northern coastline, and the other covering the rest of the continent and Tasmania. We know so little, because very little of the DNA of modern Aboriginal groups has been sampled.

"We may be able to correlate the genetic information with Aborigines' own stories -- they have incredibly complex songs, and the melodies of different groups have intersected and shifted over time. It would be very interesting to look at the relationships between the songs and genetic patterns."

Wells said another major question was where modern humans originated as a species. While the diaspora is assumed to have begun in north-eastern Africa, the sub-Saharan regional director of the Genographics Project believes they may have evolved in southern Africa, where the deepest Y-chromosome and mitochondrial lineages are found in the San Bushmen of the Kalahari Desert.

The DNA of some 15,000 to 20,000 Europeans has been sampled in recent decades, with no evidence for the controversial idea that the Cro-Magnon ancestors of modern Europeans may have hybridised with Europe's original Neanderthal inhabitants.

But if hybridisation was so rare, what odds that a cave in Portugal would yield the remains of a young boy who is clearly a modern human/Neanderthal hybrid? Wells said science has recovered mitochondrial DNA from Neanderthal remains -- and more extensive sampling of modern Europeans could yet provide surprises.

Wells said very little is known about patterns of human genetic diversity across much of South America -- sampling has been largely restricted to the Amazon Basin, the west coast and the southern tip of the continent.

More extensive sampling could confirm -- or rule out -- a controversial idea that seagoing colonists from the southern Pacific may have made landfall in South America before the first Amerindians arrived some 15,000 years ago. Charles Darwin's Voyage of the Beagle describes the now-extinct people of Tierra del Fuego as being of non-Amerindian appearance.

Intriguingly, Darwin reported that the Fuegians spoke a guttural language punctuated by 'click' sounds, unlike any they had heard previously. The Bushmen and other Khoisan peoples speak 'click' languages, hinting that the first modern humans to leave Africa may also have been 'click' speakers.

Some of the earliest paleo-Indian remains found in North America, such as Washington's Kennewick Man, and skeletons found in Nevada's Spirit Cave, have a distinctly European appearance. Wells suspects this reflects the fact that early immigrants shared a common ancestry with the peoples of central Asia, who were also the ancestors of the Europeans.

Did the armies of Alexander the Great leave their Macedonian genetic imprint in Afghanistan and the Hindu Kush, just as Genghis Khan's invaders left their stamp on eastern Europe? How far did ancient Phoenicians mariners range from their base in the Mediterranean?

These are all questions capable of being resolved by the Genographics Project, Wells said.

In addition to sampling the world's pure cultures, the project is also inviting individuals to purchase their own test kits and submit DNA samples for analysis -- and an insight into their own ancestry. The test kits will help fund the huge project.

Males potentially could trace their male ancestors' peregrinations after leaving Africa, from Y-chromosome markers, while females of European ancestry will be able to determine, from their mitochondrial DNA markers, which of the putative 'seven daughters of Eve' was their ultimate maternal ancestor.

The test kits will be processed by a US-based genealogy company, which Wells declined to name. But he said the company had the resources to deal with thousands of samples per week if, as organisers anticipate, the project captures the public imagination.

"People are fascinated by DNA, and by science in general - the cool thing is that this project ties together high technology, science, and linguistics to synthesise a view of the past," he said.

Taking part

The Genographic Project's 10-person advisory board includes Australian lawyer and indigenous advocate Tammy Williams. Her mother, Lesley, herself an eminent indigenous community activist and leader, addressed the project's Sydney launch.

"I want to reassure indigenous people who have always had suspicions connected with scientists and research," she said, before talking about aspects of her own life growing up at Cherbourg, one of the largest government settlements for Aboriginal people in Queensland.

Aboriginal people carried 'social history' cards, which specified the bearer's name, sex, religion and 'breed' -- full-blood, half-caste and so on. "Every aspect of our lives was documented," Williams explained. But it wasn't until freedom of information legislation was introduced in Queensland in 1989 that Aboriginal people were able to access their own data. Williams said she was excited about the Genographic Project "because not only are we research subjects, but we're also invited to participate".

Federal MP Daryl Melham, a former shadow minister for Aboriginal and Torres Strait Islander affairs, said he would not have been interested in a "middle-class, feel-good project". But Genographic, he said, could help to diminish prejudice in the community.

"It can get information into the public domain that can influence the community, and politicians," he said. "This is a history that's not subject to be written by the victors. This is the history you can't hide."

La Trobe University geneticist Dr Robert Mitchell, one of the project's scientific advisers, said the project's approach was to ensure that indigenous people who became involved also got something out of it, in the form of more information. -- Iain Scott