Debunking myths on genetics and DNA

Thursday, April 12, 2012

Cats (and other carnivores) don't have a sweet tooth, they have a sweet pseudogene

Cats are insensitive to sweetness. Like all vertebrates, they react to smells and tastes using G-protein-coupled receptors (GPCRs), a family of proteins that "sense" molecules outside the cell surface. Depending on the molecule, GPCRs activate a series of cascade events inside the cell that triggers the appropriate cellular response.

There are five distinct flavors: sweet, salty, bitter, sour, and umami. We have different GPCRs for each different taste, and each group is encoded by a family of genes. Differences in taste perceptions reflect differences in these genes. For example, the genes encoding for the bitter taste receptors vary in sequence and number across species, most likely reflecting the ability of a certain species to detect foods that are toxic or harmful to them. Another family of genes, Tas1r, mediates the sweet taste, and one gene in particular, Tas1r2 is a psedugene in cats, which explains why they have lost the sweet taste receptor.

I've talked about pseudogenes in older posts (look here and here): the DNA is often redundant and gene duplication events occur relatively frequently throughout evolution. Sometimes a copy carries a mutation that, if advantageous, may be picked up by a selective sweep. When that happens, the older, now redundant gene copy gets silenced and becomes a pseudogene -- a no longer coding portion of DNA.

Back to cats: the fact that they possess Tas1r2, one of the genes encoding the sweet taste receptor, indicates that some "cat ancestor" had the fully functional gene and hence could detect sweet tastes. However, at some point down the line, the gene turned into a pseudogene and lost its functionality, making cats insensitive to sweet foods. Is this unique to cats? Many carnivores that have atrophied taste systems swallow their food whole and seem to be also likely to have pseudogenized taste GPCR genes (causing them to be insensitive to certain tastes). That's one of the hypothesis posed by Jiang and colleagues in a recent PNAS paper titled "Major loss in carnivorous mammals" [1].
"We found that seven of the 12 species examined from the order Carnivora -- only those that feed exclusively on meat -- had pseudogenized Tas1r2 genes as predicted. Furthermore, we confirmed our hypothesis that, in addition to the loss of Tas1r2, both the sea lion and bottlenose dolphin lack Tas1r1 and Tas1r3 receptor genes, suggesting an absence of both sweet and umami taste-quality perception. Additionally, we failed to detect intact bitter receptor genes Tas2rs from the dolphin genome, suggesting that this modality may be lost, or its function greatly reduced, in dolphins. Thus, taste loss is much more widespread than previously thought, and such losses are consistent with altered feeding strategies."
Jiang et al. sequenced Tas1r2 from 12 species within the Carnivora order and found that 5 had an intact gene, whereas 2 (the sea lion and the fur seal) had a mutation in the start codon (the first bit of the gene) that prevents it from being translated, making the gene no longer functional. Additional deletions in Tas1r2 lead into thinking that it has turned into a pseudogene in these two species. The Pacific harbor seal Tas1r2 revealed a frameshift mutation (a disruption in the "coding" into amino acids) and several early stop codons that would cause the relative mRNA to be incomplete and hence the gene defective. Similar off-reading-frame disruptive mutations were found in the remaining species (Asian small-clawed otter, spotted hyena, fossa, bottlenose dolphin, and banded linsang). With the exception of the sea lion and fur seal, none of the mutations disrupting the reading frame were shared between species. This is interesting, as it seems to indicate that the loss of functionality in Tas1r2 happened independently many times during the evolution of these Carnivora species.

They also did a phylogenetic analysis using Tas1r2 sequence data from 18 Carnivora species, of which 8 had a pseudogenized Tas1r2, and 10 had an intact one, and finally compared taste preferences between small-clawed otters (which have a defective Tas1r2) and spectacled bears (which, instead, have an intact Tas1r2). The statistician in me couldn't help but notice that they had only 2 otters and only 4 bears -- the small sample size red light went off in my head. That said, they saw that the otters saw no preference for sugar, whereas the bears showed a strong preference for both natural sugars and noncaloric sweeteners (hey, you never know, even bears may want to save a few calories here and there so they can indulge in others!). With the exception of cats, this was the first study to test taste preferences in animals with a defective Tas1r2.

Jiang, P., Josue, J., Li, X., Glaser, D., Li, W., Brand, J., Margolskee, R., Reed, D., & Beauchamp, G. (2012). From the Cover: Major taste loss in carnivorous mammals Proceedings of the National Academy of Sciences, 109 (13), 4956-4961 DOI: 10.1073/pnas.1118360109

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