Provocarea matematica a lui Darwin – II

Asadar, avem o populatie de veverite formata din mai multe specii sau sub-specii, care s-au diversificat prin mutatii aleatorii. Patru nucleotide in grupe de cate trei formeaza 64 de combinatii, care codeaza 20 de aminoacizi. La fiecare ciclu de reproducere, se produc recombinari minore in ordinea nucleotidelor. Deci se schimba lanturile de aminoacizi din proteine. Veveritele sunt facute din proteine. Veveritele se schimba. Restul stim de la Darwin.

Incepand din Pleistocenul timpuriu (peste 2,5 milioane de ani) veveritele s-au diversificat prin acest proces. Asa ne spun biologii. David Gelernter, profesor de informatica la Yale, spune ca nu este posibil.

Gelernter considera ca are un argument zdrobitor intr-un experiment publicat de Douglas Axe in the Journal of Molecular Biology: “Estimating the Prevalence of Protein Sequences Adopting Functional Enzyme Folds” (Axe, J Mol Biol 341, 1295-1315, 2004). 

Axe a supus la mutatii aleatorii o enzima (penicilinază) care confera rezistenta bacteriilor prin inactivarea antibioticelor din familia penicilinei. Scopul a fost sa identifice frecventa secventelor de 10 aminoacizi rezistente intre toate mutatiile obtinute. Concluzia lui a fost ca numai 1/10^64 din secventele rezultate au fost funcționale. 

Inapoi la Gelernter.

Douglas Axe did a series of experiments to estimate how many 150-long chains are capable of stable folds—of reaching the final step in the protein-creation process (the folding) and of holding their shapes long enough to be useful. (Axe is a distinguished biologist with five-star breeding: he was a graduate student at Caltech, then joined the Centre for Protein Engineering at Cambridge. The biologists whose work Meyer discusses are mainly first-rate Establishment scientists.) He estimated that, of all 150-link amino acid sequences, 1 in 1074 will be capable of folding into a stable protein. To say that your chances are 1 in 1074 is no different, in practice, from saying that they are zero. It’s not surprising that your chances of hitting a stable protein that performs some useful function, and might therefore play a part in evolution, are even smaller. Axe puts them at 1 in 1077. In other words: immense is so big, and tiny is so small, that neo-Darwinian evolution is—so far—a dead loss. Try to mutate your way from 150 links of gibberish to a working, useful protein and you are guaranteed to fail. Try it with ten mutations, a thousand, a million—you fail. The odds bury you. It can’t be done.

Trec peste faptul ca Gelernter extrapoleaza rezultatele experimentului pe o secventa de zece aminoacizi la orice mutatie si orice proteina, ignorand concluziile altor experimente. Din 2004 s-au intamplat multe, printre altele problema globala a bacteriilor care au evoluat rezistenta la antibiotice. Dupa Axe, fenomenul nu ar trebui sa existe pentru ca orice mutatie in genele care codeaza penicilinaza ar trebui sa duca la rezistenta scazuta fata de antibiotice. Problema a generat insa interes pentru experimente similare cu al lui Axe si o simpla cautare pe Google este suficienta pentru a le gasi. 

Ofer doar primul titlu obtinut la prima cautare. 

Plasmid-Mediated Resistance to Third-Generation Cephalosporins Caused by Point Mutations in TEM-Type Penicillinase Genes. 

Abstract

(Sariti la ultima fraza daca nu aveti rabdare).

Infections due to strains of Klebsiella pneumoniae, Escherichia coli, and Citrobacter freundii resistant to third-generation cephalosporins have been observed recently in France and the Federal Republic of Germany. This resistance phenotype is due to the production of new plasmid-mediated, broad-substrate-range β-lactamases designated TEM-3 to TEM7. DNA-DNA hybridization analysis with a probe specific for TEM-1 indicated that the corresponding genes blaT-3 to blaT-7 were variants of the structural genes for TEM-type β-lactamases. In the present studies, a 2.5-kilobase BamHI plasmid DNA fragment encoding TEM-3 was cloned in E. coli, and the entire nucleotide sequence of blaT-3 was determined. The deduced amino acid sequence of TEM-3 differed in two positions from that of the TEM-2 enzyme: lysine (TEM-3) was substituted for glutamic acid (TEM-2) at residue 104and serine (TEM-3) for glycine (TEM-2) at residue 238 in the numbering system of Ambler. Spontaneous mutants of TEM penicillinases with increased activity against third-generation cephalosporins were obtained in vitro by selection on cefotaxime or ceftazidime. It therefore appears that mutations in TEM-type β-lactamases contribute to resistance to new-generation cephalosporins.

Cum se explica rezultatul lui Axe?  Ne explica Arthur Hunt in Panda’s Thumb. Pe scurt, Axe nu a folosit mostra originara de penicilinaza ci cea mai instabila secventa intre mai multi cloni mutanti. Apoi a extrapolat rezultatele la tot lotul. E inutil sa adaug ca Axe nu a facut nici un experiment pe bacterii ci pe o enzima izolata. Gelernter suna intimidant cu cifrele lui si aerul de exactitate dar socoteala nu iese in viata reala. Cand ai de a face cu un domeniu atat de complex este mai bine sa dai expertului beneficiul indoielii.