Sweat mutation may have helped humans colonise Asia
Washington: A single mutation produced several traits common in East Asian peoples, from thicker hair to denser sweat glands, according to researchers.
An international team of researchers, led by researchers from Harvard Medical School, Harvard University, the Broad Institute of MIT and Harvard, Massachusetts General Hospital, Fudan University and University College London, has modelled the spread of the gene mutation across Asia and North America, concluding that it most likely arose about 30,000 years ago in what is today central China.
Previous research in Pardis Sabeti`s lab at Harvard University had identified the mutation as a strong candidate for positive selection. That is, evidence within the genetic code suggested the mutant gene conferred an evolutionary advantage, though what advantage was unclear.
The mutation was found in a gene for ectodysplasin receptor, or EDAR, part of a signalling pathway known to play a key role in the development of hair, sweat glands and other skin features.
While human populations in Africa and Europe had one, ancestral, version of the gene, most East Asians had a derived variant, EDARV370A, which studies had linked to thicker scalp hair and an altered tooth shape in humans.
The ectodysplasin pathway is highly conserved across vertebrates - the same genes do similar things in humans and mice and zebrafish. For that reason, and because its effects on skin, hair and scales can be observed directly, it is widely studied.
This evolutionary conservation led Yana Kamberov, one of two first authors to reason that EDARV370A would exert similar biological effects in an animal model as in humans.
Kamberov developed a mouse model with the exact mutation of EDARV370A - a difference of one DNA letter from the original, or wild-type, population. That mouse manifested thicker hair, more densely branched mammary glands and an increased number of sweat glands.
"This not only directly pointed us to the subset of organs and tissues that were sensitive to the mutation, but also gave us the key biological evidence that EDARV370A could have been acted on by natural selection," said Kamberov.
The findings prompted the team to look for similar traits in human populations. When co-first author Sijia Wang and the team including collaborators at Fudan University examined the fingertips of Chinese volunteers at colleges and farming villages, they found that the sweat glands of Han Chinese, who carry the derived variant of the gene, were packed about 15 percent more densely than those of a control population with the ancestral variant.
And computer models suggest that the derived variant of the gene emerged in central China between 13,175 and 39,575 years ago, with a modal (most likely) estimate of 30,925 years.
Researchers concluded the derived variant is at least 15,000 years old, predating the migration from Asia by Native Americans, who also carry the mutation.
If changes to the sweat glands conferred an advantage in new climates - one of the theories the researchers plan to explore further - changes to hair and to mammary glands could have conferred other advantages at other times.
"We don`t know which of the many traits were advantageous in the past. It is easy to imagine that thicker hair, tooth shape, more sweat glands or some other associated skin features could have increased fitness, but for quite different reasons," said Professor Mark Thomas, UCL Research Department of Genetics, Evolution and Environment, and an author on the paper.
By leveraging the power of diverse fields, the team is piecing together the foundation for understanding how selected mutations like EDARV370A have impacted human diversity. But, the authors say, this is only the beginning.
The findings are reported in the cover story of the latest issue of Cell .
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