Thursday, December 21, 2006

Bruce Lahn profile in Science   posted by p-ter @ 12/21/2006 10:18:00 PM

The week's Science has a two-part profile on Bruce Lahn which includes some new information on research into ASPM and microencephalin. One of the two articles in entirely devoted to the flurry of articles disputing various claims about the two genes. Full text below the fold.
Some of Bruce Lahn's provocative claims are running into heavy fire. Last year, the University of Chicago geneticist reported, in two papers in Science, that he had uncovered genes that are still evolving in humans, and he suggested that they confer a brain-related boost--perhaps even a cognitive one. His university even applied for patents on a test that would reveal whether individuals carry the possibly advantageous genetic variants. Some researchers have since argued, however, that selection may have favored the variants for a non-neural function. Others have questioned whether the variants were under recent selection at all. And Lahn's own work with other scientists has failed to correlate variants of the genes ASPM and microcephalin with IQ. At this point, concedes Lahn, "we don't know what the variants do."

Soon after the Science papers were published, Lahn set out to see whether the variants give a cognitive advantage. In one study, Lahn helped controversial psychologist Philippe Rushton of the University of Western Ontario in London, Canada, test whether people who carry the favored variants have higher IQs. Rushton is well known for his claims that African Americans have lower intelligence than whites, and Lahn had found that some genetic variants are common in Europeans and Asians but less frequent among sub-Saharan Africans. But Rushton reported last week at the annual meeting of the International Society for Intelligence Research in San Francisco, California, that he had struck out: The variants conferred no advantage on IQ tests. "[We] had no luck," Rushton told Science, "no matter which way we analyzed the data." Lahn was not a co-author, but his group genotyped the 644 adults of differing ethnicity in the study.

Lahn is a leading author, however, of a similar international study of about 2500 subjects. Most of the results are unpublished, but findings from Australia were presented at a meeting in Brisbane last August. Nicholas Martin's team at the Queensland Institute of Medical Research in Brisbane found no statistically significant correlations between the supposedly favored variants and IQ. In large part due to this raft of negative results, Lahn says, the patenting effort has now been dropped.

If the variants aren't boosting IQ scores, what are they doing? Some mutations in microcephalin and ASPM lead to microcephaly, or very small brains, so Lahn had hypothesized that the variants might influence brain growth in normal people. But that idea was challenged last May by neuroscientist Roger Woods of the University of California, Los Angeles. Woods's team found no correlation between brain volume and the variants in 120 normal subjects, as reported in Human Molecular Genetics. Woods suggested--and Lahn agrees--that the variants might be involved in some more subtle neurological function, with Lahn arguing that a brain-related function is still the most likely target of selection.

But genome researcher Chris Ponting of the University of Oxford, U.K., notes that microcephalin and ASPM are also expressed outside the brain. In last May's issue of Bioinformatics, he reported that part of ASPM's DNA sequence resembles that of genes involved in the function of flagella, which propel sperm. Earlier work had shown that ASPM is expressed during sperm production. Ponting suggests that natural selection might have acted on flagellar function rather than brain growth. "These genes could well have many functions in many parts of the body," Ponting says, "and any one of these could have driven their adaptive sequence changes."

Meanwhile, other researchers have questioned the basic finding that the variants have been under recent natural selection. In a Technical Comment published 14 July online in Science, Sarah Otto of the University of British Columbia in Vancouver, Canada, and colleagues argued that Lahn's findings reflected not a signature of selection but rather the genetic traces of population movements as modern humans migrated out of Africa. And in October, a team led by geneticist David Reich of the Broad Institute in Cambridge, Massachusetts, reported at the meeting of the American Society of Human Genetics that it found no evidence for recent selection on ASPM when it used a method of analysis it considered superior to Lahn's. But Lahn, who is familiar with Reich's results, stands by his conclusions: "Their method has lower resolution … and is less reliable," he says.

All the same, Lahn says he has mixed feelings about the failure to date to correlate the variants of microcephalin and ASPM with differences in intelligence: "On the scientific level, I am a little bit disappointed. But in the context of the social and political controversy, I am a little bit relieved."
It's always been clear (from a scientific standpoint) that the claims of an IQ link were premature, at best (and indeed, there's no talk of it in the papers), and as Dr. Lahn noted in his 10 questions, his other speculations are clearly labeled as such. But the claims that the variants are not at all under selection are probably specious. The technical comment published in Science was essentially crap, and it's impossible to so far impossible to judge the other, unpublished results. Time will tell, time will tell...