Thursday, July 31, 2008

Could life play fairy chess?

[This is a snippet from the cutting room floor of the Rough Guide to Evolution, rejected by the editors for being too long and too technical for the educated layperson. I like to think that most blog readers are a cut above the average, so I posting it here]

Thomas Huxley once likened the world to a chessboard, in which the pieces were the phenomena of the universe and the rules the laws of Nature. Shortly after teaching my children the rules of chess, I let slip that there was a variant of chess, named fairy chess, in which one was allowed to vary the rules just slightly. Soon afterwards, whenever my son was stuck in an awkward chess position, he would make an illegal move to get out of trouble and then confidently declare that he was playing fairy chess! 

Fairy chess is almost identical to conventional chess, except that one feature of the standard game is changed, for example, by altering the layout of the board (making it a cylinder or torus), by introducing non-standard pieces, such as the grasshopper (a kind of hobbled queen that can moves along ranks, files, and diagonals but only if it can hop over another piece to reach its destination), or the nightrider (a kind of super-knight that can make an unlimited number of knight moves in any direction) or by modifying the rules (e.g. in Andernach chess, a piece changes colour after capturing another piece, while in Einstein chess, a piece is demoted with every move unless it captures another piece, in which case it is promoted).

If we adapt Huxley’s metaphor to molecular biology, life can be seen as a biochemical game of chess, in which the behaviour of the molecular pieces is seemingly governed by universal rules. In the DNA of all living organisms, the same deoxyribose-phosphate backbone is always used, with the same four “standard” bases. And the deoxyribose is consistently in the right-handed D-sugar form, never in the mirror image L-DNA form. The same genetic code is used everywhere (aside from occasional minor changes in organelles, and rare changes elsewhere), and always according to the same principle: three-base codons read consecutively into amino-acids by the tRNA-ribosome combination. The same twenty “standard” amino acids are added to proteins by the ribosome in all organisms (with just three additional spare amino acids used only in some organisms: N-formylmethionine, selenocysteine and pyrrolysine). And the amino acids handled by the ribosome are always in the left-handed form, never the mirror image D-amino acids. 

The evolutionary explanation for the universality of life’s pieces and rules is universal descent from a common ancestor. But the forcefulness of this argument depends on whether the pieces and rules could have been different. Could life play fairy chess? Evidence from the natural world and from the laboratory suggests the answer is yes!

Even in natural organisms many alternatives to the standard building blocks exist. The ribosome uses less than two dozen “standard” amino acids to build proteins, but several hundred “nonstandard” amino acids are used by living organisms in other settings (for example, the amino acid gamma-aminobutyric acid is used as a neurotransmitter); many find their way into proteins by modifications to standard amino acids after the ribosome has finished its work (the amino acid citrulline is created from arginine in this way). Similarly, although in nature DNA is always made by a polymerase from the same four standard bases (adenine, guanine, thymine and cytosine), over a hundred non-standard bases are used in tRNA molecules, with many non-canonical base pairings.

However, it is from the laboratory that the most compelling evidence for the “life didn’t have to be this way” argument comes. For a start, scientists have created many alternatives to the standard DNA backbone. Peter Nielsen from the University of Copenhagen has created peptide nucleic acids, in which the four standard bases are used in canonical base pairings, but the backbone is created from amino acids. Swiss biochemist Albert Eschenmoser and others have created nucleic acid backbones using alternatives to deoxyribose—examples include homo-DNA (which contains a six-carbon sugar, instead of the conventional five-carbon sugar), pyranosyl-RNA (pRNA), threose nucleic acid (TNA), and, simplest of all, glycerol nucleic acid (GNA). In each case, conventional pair bonding of bases remains possible (although structural studies have shown why conventional DNA may be preferable to homo-DNA).

Several groups have shown that it is possible to expand the alphabet of bases used in standard nucleic acids—Japanese biochemist Ichiro Hirao has even created unnatural base-pairs (y-s instead of A-T or G-C) that can be transcribed by RNA polymerases in a template-dependent fashion and then translated using artificial tRNAs to add a non-standard amino acid (chlorotyrosine) to the resulting protein. Floyd Romesberg at the Scripps Research Institute has created artificial base pairs do not rely on hydrogen bonding. Peter Schultz, also at the Scripps Research Institute, has created several “fairy chess biochemistries” which include oddities such as quadruplet codons. He has made yeast and bacteria that incorporate non-standard amino-acids into their proteins, and has even evolved several novel tRNA synthetases that couple non-standard amino acids to tRNAs.

Thus, there is strong evidence that the biochemical building blocks of life, and the rules used to assemble them, could have been different: life could have played any one of a myriad varieties of fairy chess. Given that any hypothetical intelligent designer would have had such a rich palette to draw upon, the very paucity of variation at the molecular level provides compelling evidence that instead of each being independently designed, all living organisms have evolved from a common ancestor. 

But, to return to the topic of a previous post,  the ultimate proof will come when we discover or create the biological equivalent of the Klingon: an organism devoid of any historical link with natural terrestrial life. This might seem a long shot, but I would bet on this becoming a reality in my lifetime.


No comments: