The 64 ques­tion that’s cen­tral to life

Cosmos - - Spectrum -

The struc­ture of DNA in­di­cates that ev­ery species on Earth is de­scended from a sin­gle com­mon ances­tor. But what if there are ex­cep­tions?

SINCE AN­CIENT GREECE it has been ap­pre­ci­ated that pat­tern and form per­vade the liv­ing world, from the ar­range­ments of leaves to the spi­ral shapes of shells. But it was only in the mid-twen­ti­eth cen­tury that sci­en­tists dis­cov­ered math­e­mat­ics at the very core of life.

In 1952 Fran­cis Crick and James Wat­son dis­cov­ered the fa­mous dou­ble helix struc­ture of DNA, in which the in­struc­tions for all known life are in­scribed. The vi­tal in­for­ma­tion is stored as se­quences of four mol­e­cules, called bases, best-known by their let­ters A,C, G and T. Rather than words, the let­ters spell out a math­e­mat­i­cal code.

A key func­tion of DNA is to spec­ify the man­u­fac­ture of pro­teins, the work­horses of bi­ol­ogy. Pro­teins are made from small mol­e­cules, amino acids, strung end to end, typ­i­cally sev­eral hun­dred in to­tal. There are dozens of pos­si­ble types of amino acids, but life uses only 20. The prop­er­ties of a given pro­tein de­pend on the pre­cise se­quence of amino acids that form it, and that se­quence is spec­i­fied by a seg­ment of DNA. Trans­la­tion be­tween the fourlet­ter alphabet of DNA and the 20-let­ter alphabet of pro­teins re­quires a code. Known sim­ply as the ge­netic code, it was cracked in the 1960s.

If life used only four amino acids the arith­metic would be sim­ple: each base could stand for a dif­fer­ent pro­tein. But to ac­com­mo­date 20, the bases are grouped into triplets: ACT, GCA and so on. Each triplet is called a ‘codon’. There are 64 pos­si­ble codons, which is more than enough to spec­ify 20 amino acids. As a re­sult, there are plenty of spare codons. Some are used for punc­tu­a­tion, but the rest code for the same 20 amino acids, im­ply­ing a lot of re­dun­dancy. For ex­am­ple, the amino acid argi­nine is spec­i­fied by six dif­fer­ent codons: CGT, CGC, CGA, CGG, AGG, and AGA.

One of the most strik­ing fea­tures of life on Earth is that the ge­netic code used by all known or­gan­isms is strik­ingly sim­i­lar, with few dif­fer­ences across species, im­ply­ing it was used by the com­mon ances­tor of all life, bil­lions of years ago. Given the com­bi­na­to­rial pos­si­bil­i­ties of spec­i­fy­ing 20 amino acids from 64 codons, there are more po­ten­tial codes than there are atoms in the uni­verse, which prompts the ques­tion of whether the ac­tual codes in use are spe­cial in some way.

Look again at the list of six codons that spec­ify argi­nine – each dif­fers from its neigh­bours by a sin­gle let­ter. And the other two codons start­ing with AG en­code ser­ine, an amino acid chem­i­cally sim­i­lar to argi­nine. So if a mis­take oc­curs in trans­la­tion the pro­tein is still likely to end up with argi­nine or a min­i­mally dis­rup­tive sub­sti­tu­tion.

Look­ing across all the pro­tein fam­i­lies, the code we ended up with seems to be par­tic­u­larly for­giv­ing of mis­takes.

If the code is op­ti­mised for ro­bust­ness, then nat­u­ral se­lec­tion must have cho­sen it among less ef­fi­cient com­peti­tors. And that im­plies it hasn’t al­ways been fixed, but co-evolved with prim­i­tive life. Which raises a fas­ci­nat­ing pos­si­bil­ity. Might there still ex­ist micro­organ­isms us­ing an ear­lier, sim­pler ver­sion?

Such ‘liv­ing fos­sils’ could eas­ily have been over­looked be­cause searches for novel mi­crobes are cus­tomised to spot the code as we know it and would not pick out any ‘aliens’. If a prim­i­tive form of life re­stricted its pro­tein com­po­nents to, say, 10 rather than 20 amino acids, then a dou­blet code in­volv­ing pairs rather than triplets of bases would suf­fice, pro­vid­ing 16 codon pos­si­bil­i­ties. Find­ing such or­gan­isms would be the big­gest ad­vance in bi­ol­ogy since Dar­win.

An even more in­trigu­ing idea is that the code con­tains hid­den math­e­mat­i­cal pat­terns.

Peter Jarvis of the Univer­sity of Tas­ma­nia pre­sented ev­i­dence some years ago that a prop­erty known as su­per­sym­me­try – a par­ti­cle physics con­cept for uni­fy­ing par­ti­cles of mat­ter, like elec­trons, with par­ti­cles that con­vey na­ture’s forces, such as pho­tons – lies buried in the ar­range­ment of the 64 cod­ing as­sign­ments. Why such a pat­tern would be em­bed­ded in the code of life is a com­plete mys­tery.

Be­cause the ori­gin of the code, along with that of life, is lost, there is plenty of scope for spec­u­la­tion. Is there a code within the code, point­ing to deep or­gan­i­sa­tional prin­ci­ples yet to be un­cov­ered?

Is 64 merely the tip of a nu­mer­i­cal ice­berg con­ceal­ing a web of math­e­mat­i­cal sub­tleties? The Greek philoso­phers would surely have agreed: to para­phrase Pythago­ras, num­ber is within all liv­ing things.

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