James Watson's controversial remarks last week about the supposed differences in intelligence between black Africans and white Westerners generated a global furore that has yet to die down. Understandably, given the history of the past few centuries, from the slave trade to Nazi-style eugenics, the subject of racial differences is highly sensitive. But the study of genetic differences between racial types is producing a revolution in the understanding of human origins and the causes of diseases ranging from disorders of the heart and the brain to multiple sclerosis and diabetes.
A huge international effort is under way to tease apart geographical variations in human DNA, and the latest results are published in the current issue of the journal Nature. Known as the HapMap Project, it is a detailed analysis of the entire genomes of 270 people from four branches of humanity – Americans of white European stock, Han Chinese, Japanese, and the Yoruba of West Africa. Although such studies are still in their infancy, the findings are already generating much excitement, and there are plans to extend the analysis to 1,000 people drawn from a wider racial spread, such as the Luhya and Masai of East Africa, the Tuscans of Italy, the Gujarati of India and Mexicans living in Los Angeles.
When the early draft of the human genome was finished in 2000 it was widely assumed that all humans alive today were 99.9 per cent genetically identical. Politicians such as Bill Clinton embraced this: "Science has confirmed what ancient faiths have always taught: the most important fact of life is our common humanity," he said in his 2000 State of the Union Address.
Further analysis of the genomes of different people, however, showed that things were more complex. It seemed that 99 per cent of the human genome does behave in a rather predicable manner. But there is a very important portion of DNA that varies enormously between people. And the variation is not simply the result of differences in DNA sequences – the order in which the genetic alphabet is spelt out. It is also due to "structural" changes. Certain genes, for instance, are duplicated in some people, and not others. Furthermore, it also seems that some of this variation has been due to differences in evolutionary pressure between people from different regions of the world. A starch-digestion gene, for instance, appears to be duplicated in people whose traditional diet is rich in starch.
The HapMap project is based on the analysis of the smallest possible changes to the DNA sequence – called single nucleotide polymorphisms (SNPs) – where one "letter" of the genetic alphabet is substituted by another. The principal reason why one person can be so different to another is largely down to these cumulative differences in SNPs. Scientists believe that analysing SNPs can explain why some people, for instance, develop conditions such as cancer and heart attacks, and why some patients respond badly, or not at all, to life-saving drugs.
The other part of the HapMap Project analysis looks at relatively short stretches of DNA that seem to have survived the genetic shuffling process. These DNA fragments are known as haplotypes and one way of imagining them is to think of a pack of cards with smaller subgroups of cards which tend to stick together during shuffling.
The point about haplotypes is that they can be used to look at common ancestors, as well as disease-causing genes. "We can identify, among apparently unrelated individuals, chromosome segments that clearly have been inherited without change from common ancestors who lived hundreds to a thousand years ago," says Mark Daly, of Massachusetts General Hospital, and a leader of the international HapMap consortium.
"The ability to detect these more recently inherited segments of DNA may hold the key to rare disease-associated variations that have been hard to detect with current tools," he says.
But looking for genetic defects that trigger disease is not the only outcome of the project. Pardis Sabeti of the Broad Institute in Cambridge, Massachusetts is analysing data to see how the human genome has evolved in different parts of the world.
In a study also published this week in Nature, Sabeti and her colleagues identify variations in the DNA of West Africans, for instance, that seem to confer resistance against Lassa fever. She has also identified in the Asian populations variations in two genes known to be involved in the formation of hair follicles and sweat glands. But this sort of analysis is only just starting.
One controversial study published two years ago investigated geographical differences in genes that are thought to be involved in brain development. Bruce Lahn, a Chinese-born American at the Howard Hughes Medical Institute within Chicago University, analysed DNA variations in the genes microcephalin and abnormal spindle-like microcephaly-associated (ASPM). Both appeared to have undergone rapid evolution during the millions of years of primate evolution that led to the human lineage. Could these genes help to explain alleged differences in human intelligence?
When he analysed the genes in present-day human populations from around the world, he found that one important haplotype of ASPM was more abundant in populations living outside Africa than in sub-Saharan populations. This led him to suggest that this variant "originated at a time that coincides with the spread of agriculture, settled cities, and the first record of written language. So, a major question is whether the coincidence between the genetic evolution that we see and the cultural evolution of humans was causative – or did they synergise with each other?"
Lahn admits that there are still major questions about the evolution of the human brain, but one clear implication of his study is that evolution may have resulted in genetic differences that influenced the intellectual capacity of geographically separated people – which is what James Watson hinted at last week in an article for The Independent.
As Lahn explains: "One can make guesses, but our study doesn't reveal how these positively-selected variants arrived. They may have arisen in Europe or the Middle East and spread more readily east and west due to human migrations, as opposed to south to Africa because of geographic barriers. Or they could have arisen in Africa and increased in frequency once early humans migrated out of Africa."
Neither is it clear how variations in these two genes can lead to differences in brain size, and what impact that may have on intellectual ability. "What we can say is that our findings provide evidence that the human brain, the most important organ that distinguishes our species, is evolutionarily plastic," Lahn says.
Sabeti says that she has not found any evidence in her haplotype analysis to support Lahn's findings, and she freely admits that this is a relief. "This is a very delicate time, and a dangerous time, as people start to come up with things that the general public, or the media, or various groups might misinterpret," she told Nature. "I like the fact that, so far, the evidence we find for natural selection in humans is only skin deep."Reuse content