Genes & brain size

This dovetails nicely with my previous post on encephalization. Brain size not linked to Microcephalin and ASMP?. Normal Variants of Microcephalin and ASPM Do Not Account for Brain Size Variability:

Normal human brain volume is heritable. The genes responsible for variation in brain volume are not known. Microcephalin (MCPH1) and ASPM (abnormal spindle-like microcephaly associated) have been proposed as candidate genes since mutations in both genes are associated with microcephaly and common variants of each gene are apparently under strong positive selective pressure. In 120 normal subjects, we genotyped these variants and measured brain volumes using magnetic resonance imaging. We found no evidence that the selected alleles were associated with increases or decreases in brain volume. This result suggests that the selective pressure on these genes may be related to subtle neurobiological effects or to their expression outside the brain.

Related: Earlier ASMP & MCPH1 articles.

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personally it suggests to me that we need to look further down the mammalian family tree (or maybe down to the vertebrate level) to see where these genes were selected for.

IIRC, mutant alleles in either of those result in truly pathological brains, not just smaller brains. Which is what we're looking for. We need alleles that produce fully functioning chimp-like brains in humans.

Looking for variations in the coding sequences of alleles is only one somewhat limited approach to looking for genetic bases of brain size variation. Taking the broader evo-devo approach and looking for differences in cis regulatory regions of important genes that influence regional cell proliferation and axon guidance cues is likely to produce a slew of likely candidate genes responsible for brain size differences.

darn tootin RJB.

it's so developmentally labile that it seems silly not to look there. obviously there was some constitutive allelic change behind the brain size increase, but we're not going to find it with any allele that results in mental retardation.

A chimp with an IQ of 70 is a wholly different thing from a human with an IQ of 70.

I've got question, representing the undergraduate crowd.

I'm a undergrad student studying evolution, writing a paper on the evolution of ASPM and MCPH1. I've been reading Lahn's papers, which argue that MCPH1' selective pressures and demographic history indicate that it underwent a bottleneck followed by strong positive selection... Currat at al. have argued otherwise, but when the dust has settled, it looks like Lahn's findings are still cast a favorable light.

But this is what seems funny to me: if you look at the map of the haplotype D frequencies around the world, the highest frequency originates in Mongolia and north-east China. Lahn writes that distribution of MCPH1 has a "starlike geneology" of distribution, originating from Mongolia?

Originating from Mongolia? Haven't I heard that Mongolia has a history of uprisings, and that as much as 80% of the Mongolian population shares their blood with Ghengis Kahn? The Mongolian state in the 1100's had a huge influence on the middle east and the developing western nations... and was a formidable threat, spreading their genes along their path of distruction

It's true, GK and his hooligans were alive a mere 800 years ago, and isn't likely to account for the world frequencies that we find today. But, maybe, just maybe, if MCPH1 has adaptive qualities (whether behavioral or otherwise), then GK's expeditions are representative of a greater behavior of the population.

I'd like to hear what other have to say about this. I haven't been able to find much literature.

By Earlham Student (not verified) on 12 Nov 2006 #permalink

Dear sir!

I have heard about the ASPM haplogroup D and its possible effect on kognition and iq. But could it be that those ASMP haplotypes of eg. east asian (northern chinese, japanese and koreans) could be of newer origin than that of ASMP haplotype D? How does Lahn estimate the age of the ASMP haplotype D and how can he be sure that it is the must recent of origin? - Is it on a phylogenetic basis where the variuos ASMP haplogroups are compared in terms genetic distance to that of the ancestrall? Can you mention which haplogroups of ASMP that are selected or most common in east asians and others?
Finally how does Lahn know that the protein structure of ASMP haplogroup D is more potent or human than those haplogroups of east asians and others?

Regards Stefan Eriksen

By Stefan Eriksen (not verified) on 22 Nov 2006 #permalink