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Gene variant linked to growth may help people survive with limited food

4 October 2021
Appeared in BioNews 1115

A variant of the growth hormone receptor (GHR) gene, known as GHRd3, has been linked to survival in times of scarce food resource.

Researchers found that Malawian children with this variation had fewer negative consequences to any severe malnutrition that they had endured. They also discovered that among the East Asian populations studied there was an estimated drop in the frequency of this variant from 85 to 15 percent over 30,000 years. Thus, this variation, which was dominant in Neanderthals, Denisovans and the ancestors of modern humans, has sharply declined in the last 50,000 years. They suggest that findings from this study could have ramifications for metabolic disorders including obesity and diabetes.

'We think that this variant is beneficial where there are periods of starvation, which was the case for most of human evolution,' says lead author Dr Omer Gokcumen, associate professor at the University at Buffalo, New York. Further speculating that 'the rapid technological and cultural advances 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.'

To further study the importance of the GHR gene, which is linked to birth weight, growth, and onset of puberty, researchers developed a mouse model with the GHRd3 variant. When subjected to a calorie-restricted diet, mice with GHRd3 were smaller at two months old, with this effect being more pronounced in males than females. Males are typically significantly larger than females, however, a calorie-restricted diet led to GHRd3 males and females being the same size. This response could be beneficial when nutritional supplies are low, as smaller bodies require less food, but when food is abundant, it may be detrimental in securing a mate.

First author Dr Marie Saitou, former postdoctoral researcher at the University at Buffalo said 'Our study points to sex- and environment-specific effects of a common genetic variant. In the mice, we observed 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'.

The paper, published in Science Advances, provides insights into our genomic past, with the combination of ancient genomic data, genome editing technologies, and advanced mathematics unravelling our biological history to aid future health developments.

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