January 16, 2007

ASPM and Microcephalin don't make people smarter

In Sep-05 a couple of papers showing that two brain genes, ASPM and Microcephalin had undergone positive selection in humans appeared in Science.

In May-06, another paper appeared that showed that Microcephalin and ASPM do not account for variability in brain size. This was a reasonable hypothesis to test, since these genes are implicated in microcephaly, a condition characterized by extremely small brains; it was thus natural to think that variation of these genes in normal subjects could also be correlated with their brain sizes; the data showed otherwise.

Now, a new study has appeared which studied the correlation of variants of these genes with IQ. As is well known, brain size only weakly correlates with IQ: in other words, by measuring how big a person's head is you get a very noisy estimate of how smart they are; other factors play a cumulatively bigger role. Since these genes are expressed in the brain, it might be possible that they worked their selective "magic" by conferring some advantage unrelated to brain size but related to IQ. However, even this is idea is also rejected by the data.

It remains to be seen what specific advantage -if any- the selected variants confer.

Hum Mol Genet. 2007 Jan 12; [Epub ahead of print]

The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.

Mekel-Bobrov N et al.

Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent samples were used, totaling 2,393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.


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