What Makes Us Humans Unique? Here Is a Surprising Answer: It's the Sugar

Dov Michaeli, MD, PhD


October 31, 2008

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What makes the human superior to the ox? So mused King Solomon, the wisest man in the 10th century BCE. Since then, this question has occupied the best minds of the human race, from Plato in the fifth century BC to modern-age molecular biologists, neurobiologists, neuropsychologists, and philosophers. Is it intelligence? Communication? Empathy? It is now evident that all these "human" traits started evolving millions of years before the first human descended from the trees to take his first tentative steps in the African savannah.

Now, Dr. Ajit Varki, a University of California, San Diego, glycobiologist, is trying to uncover the mystery of human uniqueness.[1] Glycobiology is the study of sugars, and especially oligo- and polysaccharides, in biology.

In humans the most common polysaccharide that coats the cell surface is a type of sialic acid called N-acetyl neuraminic acid. But Dr Varki discovered that we are the only animal that has this molecule exclusively. All other animals have a different sialic acid on their cell surface, called N-glycolyl neuraminic acid [Figure].

Figure. The difference between Neu5Ac and Neu5Gc: 1 oxygen atom (in green).

Dr. Varki found that a mutation in an enzyme that inserts an oxygen atom into N-acetyl neuraminic acid to make N-glycolyl neuraminic acid underwent a mutation in one of our prehuman forebears rendering it inactive, and that's how we humans ended up with N-acetyl neuraminic acid.[2]

Why did this mutation survive?

Dr. Varki offers a tantalizing clue. Plasmodium reichenowi,a malaria parasite that afflicts apes and monkeys, attaches itself to the cell surface by binding to N-glycolyl neuraminic acid, which humans don't have. So a single mutation allowed us to escape from at least 1 devastating disease, and maybe more. This is an enormous selective advantage.

So there you have it: one tiny difference in a single molecule, and what momentous consequences it has wrought.

I am Dr. Dov Michaeli of

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