Researchers scanning the genomes of African-Americans say they see evidence of natural selection as their ancestors adapted to the harsh conditions of their new environment in America.
The scientists, led by Li Jin of the Chinese Academy of Sciences in Shanghai, report in the journal Genome Research that certain disease-causing variant genes became more common in African-Americans after their ancestors reached American shores — perhaps because they conferred greater, offsetting benefits. Other gene variants have become less common, the researchers say, like the gene for sickle cell hemoglobin, which in its more common single-dose form protects against malaria. The Shanghai team suggests the gene has become less common in African-Americans because malaria is much less of a threat.
The purpose of studying African-American genomes is largely medical. Most searches for variant genes that cause disease take place in people of European ancestry, and physicians want to make sure they have not missed variants that may be more common in African-Americans and helpful for developing treatments or diagnosis.
Such searches often reveal events in a population’s history by pinpointing genes that have changed under the pressure of natural selection.
The unusually common variants identified by the Shanghai team are associated with higher risk of hypertension, prostate cancer, sclerosis and bladder cancer.
“Most of the genes associated with African-American ethnic diseases,” they write, “may have played an important role in African-Americans’ adaptation to local environment.” But the authors have not yet been able to identify the benefits they believe such genes conferred.
Mark D. Shriver, a geneticist at Penn State, said it was plausible that some versions of a gene would become more common as African-Americans adjusted to a new environment. “It’s very valid to expect that there will be factors subject to genetic adaptation and that are now more prevalent in contemporary African-Americans than in the ancestral group,” he said.
But Alkes L. Price, a geneticist at the Harvard School of Public Health, said the Shanghai team’s results, though plausible, fell short of proof. “This paper does not provide evidence of selection having occurred post-Africa,” he said.
The Shanghai researchers used a method for studying admixture, a geneticist’s term for when two populations or races intermarry; China has several such populations, perhaps accounting for the team’s interest. Using gene chips that analyze common variations in the human genome, researchers can deconstruct the chromosomes of an African-American, say, assigning each chunk of DNA to an African or European origin.
The scientists found that of the African-American genomes in their sample, 22 percent of the DNA came from Europeans, on average, and the rest from African ancestors, a figure in line with other estimates.
They then looked for sites along the genome where either European or African ancestry was present at statistically significant levels above the average, finding four regions with very common European ancestry and two with very common African ancestry. Most of these sites harbored genes of unknown function, but one, of European origin, holds a gene that combats influenza, suggesting it has become more common in African-Americans by conferring protection from the disease.
Dr. Price, however, said that two other research teams had applied the same method to African-American genomes without finding any statistically significant excess of European or African ancestry. The Chinese team, in his view, should have applied a correction factor to their statistics and, had they done so, would have obtained the same result.
In another approach, the Shanghai team focused on all the DNA segments of the African origin in the African-American genomes, discarding all the European DNA. They then compared the African component of African-American genomes with the DNA of the Yoruba of Nigeria, a well-studied population that happens to be genetically very close to the West African population from which many slaves were taken.
The Shanghai team then asked how the African genome had changed after Africans arrived in the United States. They found that versions of some genes had become more common and others less so. The less common genes included several known to be involved in protection against malaria.
Dr. Price, however, said the decrease in gene frequency might have another explanation — the fact that resistance to malaria varies in strength in different regions of West Africa. The Shanghai team may be looking at the difference in malaria resistance between the Yoruba and other African populations, not the difference between today’s African-Americans and their African ancestors, he said.
Researchers can analyze the ancestry of admixed populations because of the way the hereditary material is shuffled between generations. People have a double set of chromosomes, of which one member of each pair comes from the mother and one from the father. When the egg or sperm is made, the maternal and paternal copies of a chromosome line up and swap large chunks of DNA.
The swapped segments are so large that it takes many generations before they are whittled down to a length too small to be recognized. Meanwhile, the ancestry of each segment can be identified from its pattern of single-nucleotide polymorphisms, or SNPs, the sites on the human genome where there is commonly variation in the A, T, C and G units that make up DNA.
Among human populations, there are very few absolute differences, meaning those in which all members of one population will have, for example, unit T at a site and all members of another will have unit G. But populations do have characteristic percentages. Among Europeans, 70 percent may have C and 30 percent A at a particular SNP site, whereas in Africans the ratio may be 40 percent C and 60 percent A. So a section of genome with C at this SNP site is somewhat more likely to be European.
This is hardly decisive in itself. But take a row of 10 SNPs, and if European ancestry is more likely for most of them, then that section of DNA is probably European in origin.
Geneticists can thus deconstruct the genomes of admixed populations into a mosaic in which each segment can be traced back to one or the other of the two parent populations. This is the basis of the Shanghai team’s approach. But proving that natural selection has been at work in very recent times — in this case, the last 300 years — is very difficult, because the traces of selection are still small. To be sure of detecting such weak selection signals, Dr. Jin and his colleagues conclude, researchers in the future should analyze many thousands of genomes.
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