Here's a small taste of Roald Dahl's Charlie and the Chocolate Factory, a sweet story about a poor boy and his visit to an amazing candy factory…you've probably heard of it, since the new movie is getting a lot of press.

Only once a year, on his birthday, did Charlie Bucket ever get to taste a bit of chocolate. The whole family saved up their money for that special occasion, and when the great day arrived, Charlie was always presented with one small chocolate bar to eat all by himself. And each time he received it, on those marvelous birthday mornings, he would place it carefully in a small wooden box that he owned, and treasure it as though it were a bar of solid gold; and for the next few days, he would allow himself only to look at it, but never to touch it. Then at last, when he could stand it no longer, he would peel back a tiny bit of the paper wrapping at one corner to expose a tiny bit of chocolate, and then he would take a tiny nibble—just enough to allow the lovely sweet taste to spread out slowly over his tongue. The next day, he would take another tiny nibble, and so on, and so on. And in this way, Charlie would make his ten-cent bar of birthday chocolate last him for more than a month.

That's how it is published, at any rate. What if it read something like this?

Only once a year, on his birthday, did Charlie Bucket ever get to taste a bit of chocolate. The whole family saved up their money for that special occasion, and when the great day arrived, Charlie was always presented with one small chocolate bar to eat all by himself. And each time he received it, on those marvelg ynfg, jura ur pbhyq fgnaq vg ab ybatr, ur jbhyq rry onpx n gval ovg bs gur cncre jenccvat ng bar pbeare gb rkcbfr n gval ovg bs pubpbyngr, naq gura ur jbhyq gnxr n gval avooyr-whfg rabhtu gb nyybj gur ybiryl fjrrg gnfgr gb fcernq bhg fybjyl bire uvf gbathr. Gr arkg qnl, ur bhyq gnxr nabgure gval avooyr, naq fb ba, naq fb ba. Naq va guvf jnl, Puneyvr jhyq znxr uvf gra-prag one bs oveguqnl pubpbyngr ynfg uvz sbe zber guna n zbagu.

All sense of the story is lost, isn't it? That's just a garbled mess. You'd probably return it to the bookstore with loud complaints.

Here's something similar. This is the amino acid sequence for a human gene called TAS1R2; it may look like a garbled mess, too, but this sequence actually codes for an important and functional protein that you enjoy every day.

  1 mgpraktics lffllwvlae paensdfylp gdyllgglfs lhanmkgivh lnflqvpmck
 61 eyevkvigyn lmqamrfave einndssllp gvllgyeivd vcyisnnvqp vlyflahedn
121 llpiqedysn yisrvvavig pdnsesvmtv anflslfllp qitysaisde lrdkvrfpal
181 lrttpsadhh veamvqlmlh frwnwiivlv ssdtygrdng qllgervarr diciafqetl
241 ptlqpnqnmt seerqrlvti vdklqqstar vvvvfspdlt lyhffnevlr qnftgavwia
301 seswaidpvl hnltelghlg tflgitiqsv pipgfsefre wgpqagpppl srtsqsytcn
361 qecdnclnat lsfntilrls gervvysvys avyavahalh sllgcdkstc tkrvvypwql
421 leeiwkvnft lldhqiffdp qgdvalhlei vqwqwdrsqn pfqsvasyyp lqrqlkniqd
481 iswhtvnnti pmsmcskrcq sgqkkkpvgi hvccfecidc lpgtflnhte deyecqacpn
541 newsyqsets cfkrqlvfle wheaptiava llaalgflst lailvifwrh fqtpivrsag
601 gpmcflmltl llvaymvvpv yvgppkvstc lcrqalfplc fticisciav rsfqivcafk
661 masrfprays ywvryqgpyv smafitvlkm vivvigmlat glspttrtdp ddpkitivsc
721 npnyrnsllf ntsldlllsv vgfsfaymgk elptnyneak fitlsmtfyf tssvslctfm
781 saysgvlvti vdllvtvlnl laislgyfgp kcymilfype rntpayfnsm iqgytmrrd

TAS1R2 is short for "Taste receptor 1, member 2". It's part of what is called a G protein-coupled receptor, which is a protein that binds to some substance on the outside of a cell, and transforms that binding into activation of other proteins inside the cell, which then cause changes in the membrane properties of the cell that lead to an electrical signal being generated. What this protein does is detect sugar, and then instruct your taste buds to start sending nerve impulses up to your brain. When Charlie let that "lovely sweet taste to spread out slowly over his tongue", what he was experiencing was the activation of TAS1R2.

Cats don't get to experience that. If you're a cat owner, you may have noticed the general indifference cats have towards sweet things; it turns out that their TAS1R2 gene carries a substantial mutation that destroys its function, precisely analogous to my mangled version of the passage from Charlie and the Chocolate Factory above. There is a small deletion near the beginning of the sequence that chops out 247 base pairs. This deletion puts the remainder of the sequence out of register (this is called a frame-shift), turning it into non-functional nonsense, and also generating multiple stop sequences scattered throughout. The cat's TAS1R2 has been reduced to a useless pseudogene.

Here's a diagram detailing the differences between cat and human TAS1R2. The key things to note is that there are 6 solid black bars which represent the exons or protein coding regions of the gene, and that the cat has a chunk cut out of the third exon; and the red asterisks, which indicate the position of new stop codons sprinkled into exons 4 and 6. That is one dead gene.

Gene Structures of Cat Tas1r2, Human TAS1R2. The exons are shown in black (size in bp of each exon is in parentheses). The locations referred to in the vertical explanation text above the asterisks and the spade symbol indicate the position in bp within each exon. Intron sizes shown in the figure are not proportionally scaled because of the large size of Tas1r2 introns. Under each human exon is the percent similarity between each human exon and its cat counterpart at the nucleotide level. The exons for cat Tas1r2 refer to parts corresponding to human exons. The spade symbol (♠) indicates the position of microdeletion in exon 3 of cat Tas1r2. Asterisks (*) indicate the stop codon positions in exon 4 and 6 of cat Tas1r2. Note that nucleotide numbers of the exon 3 in human TAS1R2 and cat Tas1r2 are not identical.

Poor kitties. They don't even know what they are missing.

It's nice to have an explanation for why cats prefer fish to candy bars, but there's more to the story than that. It's also another piece of evidence for evolution.

The cat TAS1R2 gene has been thoroughly blasted into uselessness, but there is obviously more than one way to do that. A larger deletion that took out the whole gene would be just as effective, as would a 1 base pair deletion at the beginning of the sequence. Any random scrambling would do. So how do you explain this?

The sequence was analyzed in house cats, but the gene was also examined in samples taken from a tiger and a cheetah. They have exactly the same mutation, with stop codons mapped to exactly the same places. This is an example of "plagiarized errors ", a phenomenon that is most simply explained by common descent. The last common ancestor of house cats, tigers, and cheetahs had this mutation, and passed it on to all of its progeny.

We can also make an evolutionary prediction: I expect that lions, leopards, and lynxes will also have the same 247 base pair deletion, and a similar array of stop codons. We expect some variation—you can see that there are some variants in exon 6, for instance—but the scar of this ancient gouge in their DNA will be present in all cats.

Li X, Li W, Wang H, Cao J, Maehashi K, Huang L, Bachmanov AA, Reed DR, Legrand-Defretin V, Beauchamp GK, Brand JG (2005) Pseudogenization of a Sweet-Receptor Gene Accounts for Cats' Indifference toward Sugar. PLoS Genetics 1(1):e3.