evolgen

Zombie Labs Eat Brain Genes

Blogging on Peer-Reviewed Research

Remember the story about how we inherited the gene that gives us human brains from Neanderthals? The genetic data that were used to reach that conclusion (or a slightly less over-the-top conclusion) were part of a couple of other studies that identified signatures of adaptive evolution in genes involved in brain development. Those results were poorly criticized over a year ago, and they’ve recently come under fire yet again — and again (I’ve compiled a list of the relevant papers below the fold).

The two most recent attacks come in two different flavors. The first attack (previously discussed here) points out that, if one uses empirical data to generate a null distribution, there is no evidence for positive selection on one of the brain genes (ASPM). Now, this is not the brain gene that introgressed from an archaic lineage (that was microcephalin). The Lahn lab (the group behind the original brain gene papers and the introgression paper) argue that the data used to reach the conclusion in the dissenting paper suffer from ascertainment bias. There are a lot of technical details in both the attack and response to the attack that I have neither the energy nor the interest to get into here.

If the first attack is based on technical details, the second attack is one of philosophies. Lahn and colleagues identified strong signatures of adaptive evolution in ASPM and microcephalin, and, because these genes are expressed in the brain, they argued that these may be important genes for the evolution of the human brain. Where the first critique questions whether there is evidence for positive selection on ASPM, the second presents evidence that alleles of these genes do not influence human brain phenotypes. Mekel-Bobrov and Lahn point out that this is a far from novel result — previous studies (including one from the Lahn lab) have failed to identify any relationships between these genes and human cognition or brain morphology — and does not challenge the conclusion that positive selection shaped the evolution of these genes. What does remain an open question, however, is what phenotype natural selection was acting upon to influence the patterns of both sequence divergence and polymorphism at these loci. The negative results surrounding association of brain phenotypes with the two genes suggest that natural selection may have been acting on a different feature.


Evans et al. 2005. Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science 309: 1717-1720 doi:10.1126/science.1113722

Mekel-Bobrov et al. 2005. Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science 309: 1720-1722 doi:10.1126/science.1116815

Currat et al. 2006. Comment on “Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens” and “Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans”. Science 313: 172 doi:10.1126/science.1122712

Mekel-Bobrov et al. 2006. Response to Comment on “Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens” and “Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans”. Science 313: 172 doi:10.1126/science.1122822

Evans et al. 2006. Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage. PNAS 103: 18178-18183 doi:10.1073/pnas.0606966103

Yu et al. 2007. Comment on “Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens“. Science 316: 370 doi:10.1126/science.1137568

Timpson et al. 2007. Comment on Papers by Evans et al. and Mekel-Bobrov et al. on Evidence for Positive Selection of MCPH1 and ASPM. Science 317: 1036 doi:10.1126/science.1141705

Mekel-Bobrov and Lahn. 2007. Response to Comments by Timpson et al. and Yu et al. Science 317: 1036 doi:10.1126/science.1143658