How could walking up-right have helped in the evolution of human intelligence?

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What fuels us? October 2014

Lesson 1: Why is glucose important for the brain and body?

The most distinctive feature that separates humans from any other species on the planet is intelligence.  Human intelligence is made possible by many different mechanisms including a very large brain and high neuron density. The human brain has doubled in size since apes and humans last shared a common ancestor.  Not only is the brain large, it is also extremely energetically active, much more so than other primates.  The human brain uses 22-25% of the body’s energy and a human infant’s brain uses an astonishing 60% of the body’s energy.  However, apes, our closest evolutionary relatives, have brains that only harness 7-8% of their body’s available energy.
How did humans evolve such a highly active brain in such a relatively short time?  Some scientists believe that part of the answer can be found by understanding energy allocation, or how the body distributes its energy throughout the body.  Scientist Fedrigo and his colleagues decided to test this theory by looking at two genes in particular: SLC2A1 and SLC2A4.   SLC2A1 encodes a protein that is the primary glucose transporter in the brain while SLC2A4 encodes the primary glucose transporter in skeletal muscle.
Fedrigo and colleagues (2011) found that SCL2A1 is expressed significantly more in human brain tissue compared to that of primates (Figure 1.1).  Additionally, scientists found significantly less SCL2A4 expressed in human muscle tissue compared to that of other primates (Figure 1.2).  This data reveals that relative to apes, humans express significantly more glucose transporters in the brain, and less glucose transporters in skeletal muscle.  Humans have evolved to allocate more energy to the brain by increasing the amount of glucose transported into brain cells.

What made it possible for hominin ancestors to effectively allocate more energy to the brain?  By studying a similar phenomenon in birds, two scientists Isler and van Schaik, proposed that the evolution of bipedalism, walking on two legs, may have led to increased brain metabolism in humans.  How is this so?  Human, bipedal, walking is 75% less costly than quadrupedal and bipedal walking in chimpanzees.  By walking upright in human fashion, three-fourths of the energy previously allocated to walking could now be distributed elsewhere in the body.  These conditions would favor the survival and reproduction of individuals who expressed higher amounts of the SLC2A1 gene. Having a higher expression of this gene would increase the amount of glucose transporters in the brain allowing it to be more metabolically active. Increased energy capacity in the brain would support the evolution of higher thinking. Over hundreds of thousands of years, positive selection for such a gene could contribute to making the human brain the metabolic powerhouse that it is today.  

Increased Energy Availability

Increased Energy Availability

Reduced Bulk/More Rapid Digestion

Figure 1.3

From Fedrigo et al. (2011)

Increased Energy Availability for Brain Development

How did humans evolve to allocate more glucose to the brain? Specifically, how did the human genome change to produce an increase in SCL2A1 expression? Genes can be expressed at every level of gene processing. Transcription factors can bind to DNA, inhibiting or enhancing transcription. Additionally, gene expression can also be controlled at an mRNA level. This is what Fedrigo and colleagues focused on analyzing, mRNA. They found significant mutations in the mRNA that produces SCL2A1 in humans. These mutations occurred in a non-coding region of mRNA called the 5’Untranslated Region (5’ UTR). How could mutations in an area of mRNA that does not code for an amino acid cause enhancement of glucose transporters in the human brain? Once mRNA leaves the nucleus to translate proteins, it can only last for so long before it is degraded. The 5’ UTR region allows proteins to bind to ribosomes, which translate the message of mRNA into peptides. Thus, the mutations on the 5’UTR of SCL2A1 in human mRNA must enhance ribosome binding. The more times mRNA can be translated before it is inevitably degraded, the more a particular gene will be expressed.

5’End 3’ End

5’ UTR

5’ Cap

3’ UTR

Protein Coding Segment

Poly-A Tail

Messenger RNA

Higher expression of SLC2A1 is not the only thing that makes humans unique to all other species or that contributes to increased intelligence in humans.  There are many other theories that explain human intelligence: the development of agriculture, cooking, changes in digestion, etc. It is most likely that all these theories contributed to higher human intelligence. Yet, the theory of glucose allocation during human evolution illustrates how truly important glucose is for brain function and the role it played in making humans the unique organisms they are today.


Fedrigo, O., Pfefferle, A. D., Babbitt, C. C., Haygood, R., Wall, C. E., & Wray, G. A. (2011). A potential role for glucose transporters in the evolution of human brain size. Brain, Behavior and Evolution78(4), 315-326.
Isler, K., van Schaik, C. (2006). Costs of encephalization: The energy trade-off hypothesis tested on birds. Journal of Human Evolution, 51, 228-243.

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