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Alzheimer’s origins tied to rise of human intelligence

Factors that drove evolution of intellectual capacity also implicated in memory disorder.

Modern humans emerged about 200,000 years ago. Credit: Mahmoud Zayat/AFP/Getty

Alzheimer’s disease may have evolved alongside human intelligence, researchers report in a paper posted this month on BioRxiv1.

The study finds evidence that 50,000 to 200,000 years ago, natural selection drove changes in six genes involved in brain development. This may have helped to increase the connectivity of neurons, making modern humans smarter as they evolved from their hominin ancestors. But that new intellectual capacity was not without cost: the same genes are implicated in Alzheimer's disease. 

Kun Tang, a population geneticist at the Shanghai Institutes for Biological Sciences in China who led the research, speculates that the memory disorder developed as ageing brains struggled with new metabolic demands imposed by increasing intelligence. Humans are the only species known to develop Alzheimer's; the disease is absent even in closely related primate species such as chimpanzees.

Tang and his colleagues searched modern human DNA for evidence of this ancient evolution. They examined the genomes of 90 people with African, Asian or European ancestry, looking for patterns of variation driven by changes in population size and natural selection.

Marked by selection

The analysis was tricky, because the two effects can mimic each other. To control for the effects of population changes ― thereby isolating the signatures of natural selection — the researchers estimated how population sizes changed over time. Then they identified genome segments that did not match up with the population history, revealing the DNA stretches that were most likely shaped by selection.

In this way, the researchers looked back at selection events that occurred up to 500,000 years ago, revealing the evolutionary forces that shaped the dawn of modern humans, thought to be around 200,000 years ago. Most previous methods for uncovering such changes reach back only about 30,000 years, says Stephen Schaffner, a computational biologist at the Broad Institute in Cambridge, Massachusetts.

The analytical approach that Tang's team used is promising, he adds. “It's treating all kinds of selection in a uniform framework, and it's also treating different eras of selection in a more or less uniform way.” But Schaffner says that further research is needed to confirm that the method is broadly applicable.

Still, even the most powerful genomic-analysis methods can be limited by the vagaries of history. Asian and European people descended from a small number of people who left Africa around 60,000 years ago2, and that population bottleneck erased earlier patterns of genetic variation in Europeans. The genomes of African people allow researchers to look much further back in time, offering more information about the evolutionary changes that shaped humanity.

References

  1. Zhou, H. et al. Preprint at BioRxiv http://dx.doi.org/10.1101/018929 (2015).

  2. Li, H. & Durbin, R. Nature 475, 493–496 (2011).

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Inference of human population history from individual whole-genome sequences 2011-Jul-13

Spatial patterns of variation due to natural selection in humans 2009-Oct-13

Genetic evidence and the modern human origins debate 2008-Mar-05

Genome-wide detection and characterization of positive selection in human populations 2007-Oct-18

The effect of ancient population bottlenecks on human phenotypic variation 2007-Jul-19

Alzheimer’s Disease Genetics Fact Sheet from the US National Institute on Aging

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Rogers, N. Alzheimer’s origins tied to rise of human intelligence. Nature (2015). https://doi.org/10.1038/nature.2015.17589

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