Thursday, 9 September 2010

AGT: a marker for carnivory

It looks that there might be a marker for the adaptation to predominantly carnivourous or herbivorous diet in our ancestors. It appears that alanine-glyoxylate aminotransferase (AGT) targets two different intracellular locations. In the carnivores, AGT targets primarily mitochondria; in plant eaters, it targets the peroxisomes. Humans are omnivores and there are polymorphisms in both directions.

Interesting story about adaptation to herbivory in taxonomic Carnivora, also explaining the biochemistry. Would be interesting to see the oposite in the polar bear.

The autors cite that:
"Although in most normal humans AGT is peroxisomal, in many PH1 patients AGT is mistargeted to the mitochondria (Danpure et al. 1989). Mistargeted AGT remains catalytically active but is unable to fulfill its metabolic role of glyoxylate detoxification efficiently. As a result, oxalate synthesis increases and calcium oxalate crystallizes out, usually as stones, in the kidney and urinary tract."

Interesting, kidney stones on a vegetarian diet in people who should be eating meat instead? But it also suggests that humans might be omnivores more on the plant side...

But it is more complicated than that.

In another comparative analysis, which essentially supports the association between AGT and diet across mammals, the authors state that:
"The human, in fact, is remarkable because, after having lost the ability to target AGT to mitochondria following a single mutation to the more 5′ ancestral translation start site (Takada et al. 1990), some individuals have reacquired the ability to target a small amount of their AGT back to mitochondria. However, this is not owing to reintroduction of the ancestral MTS back into the open reading frame. Instead, it is owing to the presence of a very common polymorphism which creates a new MTS in a region downstream of the ancestral MTS (Purdue et al. 1990). Whether this reacquisition of mitochondrial AGT targeting in some humans is related to increased meat-eating is unknown."

Also here:
"Some evidence to suggest that populations with greater recent ancestry of meat eating (eg. the Saami) have higher frequencies of the allele favoring the “retargeting” of enzymatic activity to the mitochondria.
The entire article is really worth reading.

So, how do I get my AGT tested?

EDIT: Having written the above I did some more browsing and came across a highly recommended article from BeyondVeg. The autor is making a strong case against veganism, but the evidence for rapid evolution and adaptation, at least in some ethnic groups, could also support the argument for some Neolithic foods in the diet:

"A recent analysis of a major genetic database - the HapMap SNP database - has shown that human evolution has accelerated dramatically in the last 40K years BP, with adaptive evolution in the last 10K years BP occurring at a rate >100 times the rate that prevailed in most of human evolution (Hawks et al. 2007, Hawks 2007). There are two primary drivers for this phenomenon: 1) the major increase in human population caused by the agricultural revolution – a larger population base allows for a larger number of genetic mutations, 2) diversity in human cultures – diets, environments – created numerous environments with different selective pressures to filter the mutations.

The preceding suggests that more human evolution has occurred in the time since the agricultural revolution began, ~10K years BP, than in the 1 million years that preceded the date 40K BP. The conclusion here is that humans are still evolving, and very rapidly, i.e., we are very much a “work in progress” in evolutionary terms."

I like the bit about chitinase, though this is probably an old adaptation. Would chitin count as fiber? Mopane anyone? Should be high in omega-3 if leaf/grass-fed. Excellent source of protein, but I would skip the porridge in the recipe. Yummy.

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