Why Can’t Humans Produce Neu5Gc?

Ajit Varki from University of California, San Diego believes to have found out what it means to be human. He’s been investigating a molecule called Neu5Gc, a variant of sialic acid, and his progress has been summarized in this news article. Neu5Gc functions as a marker or tag which identifies cells and helps them stick together. It also helps regulate immune response.

Chimpanzees, bonobos, gorillas, orangutans are able to produce Neu5Gc, but curiously humans do not produce Neu5Gc. Humans do produce Neu5Ac, a precursor to Neu5Gc. But we do not have the enzyme that helps tack on an extra oxygen atom to make Neu5Ac to Neu5Gc. Neandertals, also, do not have the enzyme to convert Neu5Ac. Clearly there was potentially a strong human lineage specific loss of function mutation somewhere during human evolution. The Neu5Gc that is found in us is found from red meat and milk products.

Varki believes that this difference, potentially explains some of the more unusual differences between humans and apes,

“Chimpanzees do not seem to suffer from heart disease, cancers, rheumatoid arthritis or bronchial asthma – common conditions in humans. Nor do they get sick from the human malaria parasite, which uses sialic acid to latch on to our blood cells.”

He’s found that some people produce antibodies that react to Neu5Gc. When an antibody targets a foreign molecule, it triggers inflammation. This observation, seeing how Neu5Gc elicits an immune reaction to create anti-Neu5Gc antibodies, further points to some strong selection against Neu5Gc. Varki believes that the mutation that prevents processing Neu5Ac into Neu5Gc helped shrug off a particular disease.

There’s one glarring thing that this news article gets wrong. It quotes that, Varki and team,

“estimates that the genetic change first appeared up to three million years ago, which coincides with the emergence of Homo erectus, the first of our ancestors to venture out of Africa.”

Uhh, there were no Homo erectus around 3 million years ago. There were ausrtalopithecines then… but the genus Homo didn’t emerge until 500,000 years later. Regardless, there was most definately a mutation that occurred after our last common ancestor with great apes. The irony is that what may have protected our ancestors, is now partially responsible for many diseases, such as malaria and even cancer.

    Tangvoranuntakul, P. (2003). Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proceedings of the National Academy of Sciences, 100(21), 12045-12050. DOI: 10.1073/pnas.2131556100

12 thoughts on “Why Can’t Humans Produce Neu5Gc?

  1. Hmmm… are you saying that, while dogs (and other animals) can perfectly get cancer, great apes other than humans don’t? I feel quite skeptic about that on first sight but guess you know better. Just making sure: are you sure about that?

  2. I caught that too, Luis.

    I know other animals do get cancer, but as I understand it Dr. Varki thinks that since we don’t make Neu5Gc, our bodies make an anti-Neu5Gc antibody to any foreign Neu5Gc which causes an inflammatory response. This inflammatory response is associated with many cancers, such as colorectal cancers… which is not seen in animals who can produce Neu5Gc.

    Kambiz

  3. All right, thanks. I had the impression from the post you were talking of all sorts of cancer. An inflammatory response is something different, I understand, of more limited scope.

  4. Regarding Neu5Ac and absence of malaria resembles another ailment in which such a thing is seen. In sickle cell anemia trait (HbS) malarial invasion is not seen.
    Absence of Neu5Gc and presence of its antibody is analogous to the blood group antigens. For example, persons of blood group A, have A antigen; A antibody is absent.
    Sialic acid, a highly negatively charged substance found in the glycocalyx, is responsible for repulsion of blood cells, thus not allowing them to stick to the blood vessel endothelium and prevents aggregation.

  5. Can someone explain the advantage of not producing either vitamin C or Neu5Gc? So far it only seems disadvantageous–scury, malaria, stroke, increased cancer. Don’t mutations have to confer a competitive advantage to advance? With all of these competitive disadvantages how did the inability to produce these substances become part of our genetic heritage?

  6. But don’t some human populations subsist on diets lacking mammals (fish, birds, reptiles and insects and oceanic inverts)? Further, aren’t there enough people on vegan diets for and that have been doing so for long enough to get some idea of how much this Neu5Gc inflammatory response may be adversely affecting health?

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