Gene that determines size of human brain

lucaspa · #1 14th January 2004, 11:09 AM

This was in the NY Times. I'll also get the original article in case anyone wants to go into greater depth. It's got lots of good concepts that anyone interested in evolution, especially those against, should pay attention to. I've bolded those parts.

Evolution of Gene Related to Brain's Growth Is Detailed

By NICHOLAS WADE

Published: January 14, 2004

gene that helps determine the size of the human brain has been under intense Darwinian pressure in the last few million years, changing its structure 15 times since humans and chimps separated from their common ancestor, biologists have found.

The gene came to light two years ago, when a disrupted form of it was identified as the cause of microcephaly, a disease in which people are born with an abnormally small cerebral cortex.

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Dr. Bruce T. Lahn and fellow geneticists at the University of Chicago have decoded the DNA sequence of the gene in apes, monkeys and people and have identified the changes caused by the pressure exerted by natural selection. Most of the other changes in DNA units generally make no difference to the protein specified by the gene, and evolutionary forces are neutral to them.

The gene, known as the ASPM gene, has been under steady selective pressure throughout the evolution of the great apes, a group that includes orangutans, gorillas, chimpanzees and humans, Dr. Lahn and colleagues say in an article being published today in the journal Human Molecular Genetics. By contrast, the versions of the gene possessed by monkeys, dogs, cats and cows show no particular sign of being under selective pressure.

The progressive change in the architecture of the ASPM protein over the last 18 million years is correlated with a steady increase in the size of the cerebral cortex, the part of the brain responsible for higher cognitive function, during the ape and human lineage. Evolution has been particularly intense in the five million years since humans split from chimpanzees.

"There has been a sweep every 300,000 to 400,000 years, with the last sweep occurring between 200,000 and 500,000 years ago," Dr. Lahn said, referring to a genetic change so advantageous that it sweeps through a population, endowing everyone with the same improved version of a gene.

But since the last sweep, the gene seems to have been kept stable by what geneticists call purifying selection, the removal of any change that makes a significant difference to the gene's protein product, according to an independent study by Dr. Jianzhi Zhang, an evolutionary biologist at the University of Michigan. Dr. Zhang's report was published last month in the journal Genetics.

Early hominids like Australopithecus africanus, which lived some three million years ago, had a brain that weighed about 420 grams (15 ounces); modern human brains range from 1,350 to 1,450 grams, an increase that Dr. Zhang calls "one of the most rapid morphological changes in evolution." The brain of a typical patient with microcephaly is the same weight as that of an australopithecus, Dr. Zhang noted, as if disruption of the gene negated three million years of development.

Disruption of the ASPM gene was identified as a cause of microcephaly two years ago by Dr. Geoffrey Woods, a British pediatrician, and Dr. Christopher Walsh, a neurogeneticist at the Harvard Medical School. Their finding instantly caught the interest of evolutionary geneticists.

At least five other genes, yet to be identified, can cause microcephaly when disrupted by a mutation, so ASPM is not the only determinant of human brain size. But given what is now known about its evolutionary history, it does seem to be an important one. It acts during fetal development to prescribe the number of cells in the future cerebral cortex.

Most human genes exist as families of similar members, formed when one gene gets accidentally duplicated one or several times. The ASPM gene is "almost unique," Dr. Walsh wrote by e-mail, because in all known animal genomes, it has resisted the usual duplication events and been maintained as a single copy. Single-copy genes can cause serious disease if disrupted by mutation. But their advantage, in terms of evolution, is that "you only have to edit them once to create a lasting change," Dr. Walsh said."

shenzhou · #2 14th January 2004, 01:44 PM

Here is the abstract:

Genetics. 2003 Dec;165(4):2063-70.

Evolution of the Human ASPM Gene, a Major Determinant of Brain Size.

Zhang J.

Department of Ecology and Evolutionary Biology, University of Michigan, Ann
Arbor, Michigan 48109.

The size of human brain tripled over a period of approximately 2 million years
(MY) that ended 0.2-0.4 MY ago. This evolutionary expansion is believed to be
important to the emergence of human language and other high-order cognitive
functions, yet its genetic basis remains unknown. An evolutionary analysis of
genes controlling brain development may shed light on it. ASPM (abnormal
spindle-like microcephaly associated) is one of such genes, as nonsense
mutations lead to primary microcephaly, a human disease characterized by a 70%
reduction in brain size. Here I provide evidence suggesting that human ASPM went
through an episode of accelerated sequence evolution by positive Darwinian
selection after the split of humans and chimpanzees but before the separation of
modern non-Africans from Africans. Because positive selection acts on a gene
only when the gene function is altered and the organismal fitness is increased,
my results suggest that adaptive functional modifications occurred in human ASPM
and that it may be a major genetic component underlying the evolution of the
human brain.

Hint: if you are copying text from a webpage its better to paste it into notepad or similar first - it removes all the junk.

Jet Black · #3 14th January 2004, 04:08 PM

so when do we tinker with monkeys then? absolutely fascinsting discovery. I regret not doing biology now

Jet Black · #4 14th January 2004, 04:14 PM

incidentally, woudln't this have to be coupled with genes for the skull as well, or would the skull just grow to stuff it all in (possibly explaining the hole in the tops of babies heads when they are born)

David Gould · #5 14th January 2004, 06:51 PM

Originally Posted by Jet Black

incidentally, woudln't this have to be coupled with genes for the skull as well, or would the skull just grow to stuff it all in (possibly explaining the hole in the tops of babies heads when they are born)

It might just mean that the brain is packed in more tightly, which actually could be an advantage. The folding to pack it in would mean that more parts of the brain were in close proximity to one another and information exchange would become more rapid.

However, the skull case did increase in size. Maybe what we are seeing is that there was evolutionary upwards pressure on the brain size but also evolutionary downwards pressure because having a big brain in a small skull might damage your brain. But this in turn would put evolutionary upwards pressure on the size of the brain case: if you happened to have a slightly larger brain case then having a bigger brain would not be a disadvantage.

Jet Black · #6 14th January 2004, 06:58 PM

depends on the jumps I suppose. anyway I looked up some cases of microcephaly, and in those the skulls are smaller, so I suppose the actual instructions for growing a skull are quite flexible.

Philosoft · #7 15th January 2004, 02:53 AM

Originally Posted by David Gould

It might just mean that the brain is packed in more tightly, which actually could be an advantage. The folding to pack it in would mean that more parts of the brain were in close proximity to one another and information exchange would become more rapid.

I'm not sure it's so simple. Packing a more massive brain more tightly would presumably result in an increase in surface area via larger and more numerous sulci and gyri. That might actually cause parts of the brain (and thus individual cells) to move farther apart.