The Evolution of the Human Growth Hormone Receptor Gene

Written by Dr. Jonathan Peterson, Updated on March 9th, 2024, Published on June 22nd, 2022

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The field of genetics is ever-expanding and discovering new genes and how they work all of the time. Recently, more information was discovered regarding the human growth hormone (HGH) receptor gene.

HGH is a vital and important hormone for growth and overall health as we get older. It is especially important for cellular regeneration and repair, which makes it no surprise that it has been popular in anti-aging circles.

Not to mention, it helps men and women lose weight, gain muscle and regain sexual function. In children, it is one of the most important hormones because it is what helps them to grow so quickly!

HGH Receptor Gene Aids in Survival

Interestingly, genetic research is showing that a shortened version of the HGH receptor gene, GHRd3, probably helps people to survive in situations with low resources or unpredictable environments. Approximately 1-2 million years ago, gene GHRd3 emerged, being the predominant version of the gene in Neanderthal and Denisovan ancestors.

Then, more recently, during the last 50,000 years or so, that version became less prevalent with “a massive decrease in the frequency of this variant among East Asian populations,” stated Omer Gokcumen from the University of Buffalo.

The evolutionary biologist also says, “we see the estimated allele frequency drop from 85% to 15% during the last 30,000 years.” Why did the variant change? Why would it fall out of favor?

According to the research, the function of GHRd3 helps to explain why these evolutionary changes occurred, with the theory being that it helped our ancestors to cope with nutritional stress, meaning low resources and poor nutrition.

Steady Resources in Recent Centuries Changed GHRd3’s Prominence

Dr. Gokcumen also hypothesizes that “Maybe the rapid technological and cultural advances [meaning increased food resources that do not run out for most people] over the past 50,000 years have created a buffer against some of the fluctuations in resources that made GHRd3 so advantageous in the past.”

Lead researcher, Marie Saitou, from the Norwegian University of Life Sciences, says, “GHRd3 is interesting because it is a very common deletion that is variable between you and me among humans. Normally, these kinds of important fundamental genes do not change between human to human and are highly conserved in other animals even.”

So basically, the HGH receptor gene is quite variable from person to person, some of the human population has it and some of them don’t, even though this is considered an “important fundamental gene.”

It’s strange that something so important could so easily be deleted from the genetic code. But it has, as stated earlier in this article. No wonder more and more people are turning to human growth hormone replacement therapy these days. They could be lacking in adequate genes to maintain hormone balance.

The Functions of GHRd3

In essence, the HGH receptor gene helps to control the body’s response to growth hormone and activates the processes that lead to growth. In order to study how the gene changed over time, scientists compared genomes between modern humans and four archaic hominids. Three Neanderthals and one Denisovan all had the GHRd3 variant.

In addition, the scientists looked at how GHRd3 functions in modern times. The presence of the variant was associated with improved outcomes for a group of children who had experienced severe malnutrition.

In mice studies, the research supported the theory that GHRd3 helps to regulate the body’s response to scarce food sources. In fact, some male mice that had the variant had biological similarities to mice that did not have much access to food. These similarities were traits that could help them survive during times of nutritional stress.

One study put mice with GHRd3 on a low-calorie diet and when compared to mice without the variant at 2 months of age, the GHRd3 group was smaller in size. This is a good thing during times of food scarcity because smaller bodies do not need as much food to run.

The effect of GHRd3 was not as prominent in females and so male and female mice carrying the variant ended up being the same size while on a low-calorie diet when typically, males are larger than females.

Saitou describes his research as showing that “GHRd3 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.”

Females are already smaller in size and may suffer negative evolutionary consequences if they lose body weight.

Therefore, it seems likely that a genetic variant that may affect the response to nutritional stress has evolved in a sex-specific manner.

So, what does this research tell us? That human growth hormone is an incredibly important hormone, indeed!

It’s very interesting to learn about its evolutionary history but we also know that it is necessary for optimal quality of life. Have you checked your levels in the past 6 months? Better get on that.

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