Another genetic change leading to human minds

Wang Yinqiu and colleagues (2005) report on the phylogenetic history of the PACAP precursor gene in humans and closely related primates (hat tip: Dienekes). They find that human genetic sequences differ from chimpanzees by 17 amino acid substitutions, but that the sequence is highly conserved in other mammals:

Surprisingly, when the human and chimpanzee protein sequences were aligned with those of other mammalian species, 11 out of the 17 amino acid substitutions were found conserved in mouse, rat and sheep, indicating that the accelerated evolution of the PACAP precursor only occurred in the human lineage (Wang et al. 2005:7).

The amino acid substitutions on the human lineage were shared by a sample of 50 human individuals without variation, although 3 additional polymorphic sites were found in this comparison. The significance of this pattern of variation within humans was not reported; my own assessment is that the sample was not designed to test the coalescence time of the gene within humans or other attributes of the human-specific variation at the locus.

A couple of observations about the pattern of evolution of this gene strike me. First, like other genes believed to be related to human brain evolution, the role played by this one is as yet basically unknown. According to Wang and colleagues, the gene product is a neurotransmitter that appears to be involved in neurogenesis of the cerebral cortex, as reflected by its association with holoprosencephaly, a developmental defect of the forebrain. But just how the function of this gene in humans may be different from in other mammals, or how it may have led to

Second, during the course of human evolution this gene underwent not one episode of positive selection, but many -- possibly as many as 17 (or even more, counting possible reversals). It is not known whether these adaptive changes followed upon each other rapidly or not. For example, one adaptive change in the gene sequence may have set off a relatively rapid pulse of selective changes, as a spreading postively selected allele found new fortuitously adaptive combinations with rare alleles at other genetic loci. Under this scenario, the adaptive changes in the gene may have occurred during a relatively short time period. Or each amino acid substitution might reflect an independent evolutionary change in the ancient human lineage, perhaps following upon a series of changes in other genes. In this case, the distribution of times between substitutions would be essentially random, and could spread across the entire evolutionary history of the human lineage. Finding the difference between these options may be impossible, unless the interactions of PACAP with other genes can shed light on the mechanism by which putative earlier forms may have functioned.

Last year, Dorus and colleagues established that genes involved in the nervous system have experienced higher rates of evolution within hominoids, and within the human lineage in particular. This work depended upon the observation of a significant excess of amino acid substitutions across many genes. Likewise, the earlier study of the ASPM gene observed that it was likely a component of the evolution of the human brain, not because of a recent coalescence in humans, but because of evidence of multiple amino acid substitutions during human evolution. Together with the current study, these observations appear to be indicating not that there was a single, critical period of evolutionary change of human cognition, but instead that there was a succession of genetic changes at many different genes across much of the time range of human evolution.

That observation goes nicely with the fossil evidence for changes in the brain. Although this evidence is severely limited in what it can tell us about the structure and function of the brain, it is very powerful in its ability to tell us about changes in brain size. The trend in human brain sizes has involved several different periods of expansion during human evolution, including a gradual (i.e. not sudden) evolution of larger brains across the Middle and Late Pleistocene. Each instance of brain size evolution must have required concomitant changes in the genetics of brain function and development. Nor should we expect that the evolution of brain-related genes would have been limited to the time periods of brain expansion, since both behavioral and life history changes may have influenced human brain function and development without requiring expansions in brain size. In any event, the evolution of the brain was likely a more or less continuous process during human evolution, and the genetic record appears to be documenting that.


Wang Y, Qian Y, Yang S, Shi H, Liao C, Zheng HK, Wang J, Lin AA, Cavalli-Sforza LL, Underhill PA, Chakraborty R, Jin, L, and Su B. 2005. Accelerated evolution of the PACAP precursor gene during human origin. Genetics (published ahead of print) April 16, 2005. Genetics online