Key Points In Brain Evolution Identified

A research team from the Howard Hughes Medical Institute, led by Bruce T. Lahn, has uncovered some fascinating genetic pointers to the human brain’s evolution. Their findings, in the journal Science, relate to sequence variations in two genes that regulate the size of the brain in humans. Interestingly, the major variants in these genes arose at key points in human history.

The team focused on detecting sequence changes in two genes – Microcephalin and ASPM in different human populations. Mutations in either of these genes can render the gene nonfunctional and cause microcephaly – a syndrome in which the brain develops to a much smaller size than normal. Lahn and his colleagues had previously determined that both Microcephalin and ASPM showed significant changes under the pressure of natural selection during the making of the human species. “Our earlier studies showed that Microcephalin showed evidence of accelerated evolution along the entire primate lineage leading to humans, for the entire thirty to thirty-five million years that we sampled,” Lahn said. “However, it seemed to have evolved slightly slower later on. By contrast, ASPM has evolved most rapidly in the last six million years of hominid evolution, after the divergence of humans and chimpanzees.”

In order to identify the sequence changes that occurred in the evolutionary lineage leading to humans, the researchers determined the DNA sequences of the two genes among a large number of primate species and searched for sequence differences between humans and nonhuman primates. Statistical analysis then revealed the differences that drove significant sequence changes in the lineage leading to humans. Presumably, these changes accumulated because they conferred some competitive advantage.

The evidence that Microcephalin and ASPM were evolving under strong natural selection led Lahn and his colleagues to consider exploring whether these two genes are still evolving under selection in modern human populations. “In the earlier studies, we looked at differences that had already been set in the human genome,” he said. “The next logical question was to ask whether the same process is still going on today, given that these genes have been under such strong selective pressure, leading to the accumulation of advantageous changes in the human lineage. If that is the case, we reasoned we might be able to see variants within the human population that are rising in frequency due to positive selection, but haven’t gone to completion yet.”

To explore this hypothesis, the researchers first sequenced the two genes in an ethnically diverse selection of about 90 individuals. Then, the researchers sequenced the genes in the chimpanzee, to determine the “ancestral” state of polymorphisms in the genes and to assess the extent of human-chimpanzee divergence.

In each gene, the researchers found distinctive sets of polymorphisms (sequence differences between different individuals). Blocks of linked polymorphisms are known as haplotypes and each haplotype represents a distinct genetic variant of the gene. They found that they could further break the haplotypes down into related variants called haplogroups. Their analysis indicated that for each of the two genes, one haplogroup occurs at a frequency far higher than that expected by chance, indicating that natural selection has driven up the frequency of the haplogroup. They referred to the high-frequency haplogroup as haplogroup D.

The researchers found that haplogroup D of ASPM occurred more frequently in European and related populations, including Iberians, Basques, Russians, North Africans, Middle Easterners and South Asians. It was found at a lower incidence in East Asians, sub-Saharan Africans and New World Indians. For Microcephalin, the researchers found that haplogroup D is more abundant in populations outside of Africa than in populations from sub-Saharan Africa.

To improve the reliability of their data, the researchers applied their methods to a larger population sample of more than one thousand people. Confirming their earlier findings, that analysis also showed the same distribution of haplogroups.

It appears from the findings that the Microcephalin haplogroup D appeared about 37,000 years ago, and the ASPM about 5,800 years ago – both well after the emergence of modern humans 200,000 years ago. “In the case of Microcephalin, the origin of the new variant coincides with the emergence of culturally modern humans,” said Lahn. “And theASPM new variant originated at a time that coincides with the spread of agriculture, settled cities, and the first record of written language. So, a major question is whether the coincidence between the genetic evolution that we see and the cultural evolution of humans was causative, or did they synergize with each other?”

The researchers can only guess at the geographic origin and circumstances surrounding the spread of the haplogroups. “They may have arisen in Europe or the Middle East and spread more readily east and west due to human migrations, as opposed to south to Africa because of geographic barriers. Or, they could have arisen in Africa, and increased in frequency once early humans migrated out of Africa,” said Lahn.

Could selective pressure on the new variants relate to cognition? “What we can say is that our findings provide evidence that the human brain, the most important organ that distinguishes our species, is evolutionarily plastic,” Lahn explained. “Here we have two microcephaly genes that show evidence of selection in the evolutionary history of the human species and that also show evidence of ongoing selection in humans.”

It would be wrong to suppose that some ethnic groups are more “evolved” than others, Lahn emphasized. Any differences among groups would be minor compared to the large differences in such traits as intelligence within those groups. “We’re talking about the average impact of such variants,” he said. “Just because you have one gene that makes you more likely to be a little taller, doesn’t mean you will be tall, given the complex effect of all your other genes and of environment.”

Lahn said that the findings suggest that the human brain will continue to evolve under the pressure of natural selection. “Our studies indicate that the trend that is the defining characteristic of human evolution – the growth of brain size and complexity – is likely still going on. If our species survives for another million years or so, I would imagine that the brain by then would show significant structural differences from the human brain of today.”

Source: Media release – Howard Hughes Medical Institute

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