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HGH receptor gene may have helped early humans survive periods of scarcity

A variant of HGH, now rare among modern humans, may have helped Neanderthals and early human relatives survive periods of scarcity. Image by CC/Pixabay
A variant of HGH, now rare among modern humans, may have helped Neanderthals and early human relatives survive periods of scarcity. Image by CC/Pixabay

Sept. 24 (UPI) -- Today, a fresh meal is much easier to come by than it was 50,000 years ago. All that's required is a few dollars and a trip to a restaurant or the grocery story -- no scavenging or hunting is necessary.

According to a new study, the relative ease of modern life may explain why a variant of the human growth hormone receptor gene known as GHRd3 is now so rare.

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The variant, which first emerged 1 million to 2 million years ago, was dominant among Neanderthals and Denisovans, as well as the closets ancestors of modern humans. Today, however, the variant is much less prevalent.

New research, published Friday in the journal Science Advances, suggests its diminished presence among modern populations is a reflection of technological advances humans have made over the last 50,000 years.

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In the past, GHRd3 likely helped early humans and their relatives survive periods of scarcity, but material conditions for humans have improved dramatically.

The latest genomic analysis reflected this dramatic shift.

"You have a massive decrease in the frequency of this variant among East Asian populations we studied, where we see the estimated allele frequency drop from 85% to 15% during the last 30,000 years," study author Omer Gokcumen, an evolutionary biologist at the University of Buffalo, said in a press release.

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Just as their name suggests, human growth hormone receptor genes aid the reception of human growth hormone, which dictates a range of cellular processes related to growth. Genes of such import are typically conserved across species.

But while the variant was common among archaic humans, including multiple Neanderthal and Denisovans lineages, it has become a common deletion for modern humans.

It's not that GHRd3A isn't useful. According to the latest study, the presence of GHRd3 was associated with better survival and health outcomes among children facing sever malnutrition. Additional experiments showed the variant helped mice manage periods of reduced food access.

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"Our study points to sex- and environment-specific effects of a common genetic variant. In the mice, we observed that GHRd3A leads to a 'female-like' expression pattern of dozens of genes in male livers under calorie restriction, which potentially leads to the observed size reduction," said study author Marie Saitou, an investigator at the Norwegian University of Life Sciences.

"Females, already smaller in size, may suffer from negative evolutionary consequences if they lose body weight," said co-author Dr. Xiuqian Mu, associate professor of ophthalmology at Buffalo.

"Thus, it is a reasonable and also very interesting hypothesis that a genetic variant that may affect response to nutritional stress has evolved in a sex-specific manner."

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Animals have not forgone GHRd3A the way humans have, making it difficult to uncover the reasoning behind its deletion among modern humans. Advancements in gene editing technology allowed researchers to engineer mouse models without GHRd3A, revealing the effects of the variant's deletion.

"It is an exciting time for doing research on human evolution, where it is now possible to integrate data from ancient genomes, gene editing technologies, and advanced mathematical approaches to tell the human story in all its messy glory," Gokcumen said.

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