Unraveling the Co-Evolution of Human Height and Basal Metabolic Rate

Taller stature and a higher basal metabolic rate are two characteristics that distinguish modern humans from non-human primates. A genetic variant that helped these traits co-evolve was discovered by researchers and published in Cell Genomics. People who have this mutation appear to grow taller, especially if they eat a lot of meat.

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“The dietary shift from a primarily plant-based diet to increased meat consumption marks a major milestone in human evolution. Previous studies have suggested that this shift influenced many traits and phenotypes in anatomically modern humans. It is therefore not surprising that height may also have been affected,” said Jin Li and He Huang, study Co-Corresponding Authors, from Fudan University.

To find genetic correlations between height and basal metabolic rate, the researchers used the UK Biobank, which contains biological samples and genomic data from 500,000 people. They discovered over 6,000 possible causative variants.

A particular regulatory variant of ACSF3 was found to be especially promising after the probable functional effects of these variants, such as their impact on gene expression and protein sequences, were narrowed down.

Subsequent research showed that, in contrast to other apes, the variant known as rs34590044-A increases the expression of ACSF3 in the liver of contemporary humans.

In anatomically modern humans, basal metabolic rate and stature exhibit notable evolutionary divergence compared to non-human apes. Although both traits, particularly height, have been extensively investigated, the evolutionary mechanisms driving these changes remain comparatively underexplored. That is why we decided to focus on these two traits together.

Shaohua Fan, Study Author, Fudan University

To further substantiate these findings and explore their relevance to modern human traits, the team performed detailed functional analyses of the variant and its impact on ACSF3 expression using both cellular and mouse models.

While the precise mechanism by which ACSF3 influences the body is not completely understood, it appears to be associated with mitochondria, which the authors suggest accounts for its metabolic effects. Increased ACSF3 expression also seems to encourage bone formation, potentially contributing to greater height.

In a mouse model that was provided with essential amino acids typical of meat-based diets, the researchers observed that overexpression of ACSF3 resulted in both increased body length and a higher basal metabolic rate when subjected to the “meat” diet.

The team emphasizes that ongoing research involving global populations, using a combination of methodologies including multiomics, experimental technologies, computational algorithms, and diverse collections of ancient DNA, is crucial for deepening the understanding of complex evolutionary processes.

This research reveals the intricate interplay between the genetic, environmental, and demographic factors that have contributed to the emergence and evolution of anatomically modern humans. It also has important implications for understanding susceptibility and resistance in contemporary metabolic disorders like type 2 diabetes, obesity, and metabolic syndrome.

Shaohua Fan, Study Author, Fudan University

The researchers anticipate that many additional traits may have co-evolved through similar mechanisms. They intend to continue exploring the genetic foundations of metabolic homeostasis in human evolution, aiming to uncover how human ancestors adapted to various diets throughout evolutionary history.