The origin of the genetic code

Standardni genetički kod (SGC) je šifra prevođenja sekvence nukleotida u sekvencu aminokiselina na način da je svaki od mogućih tripleta (nizova od 3) nukleotida – kodon pridružen nekoj od 20 bioloških aminokiselina. SGC je gotovo univerzalan u živom svijetu, zbog čega znamo da je kao takav postojao i u posljednjem univerzalnom zajedničkom pretku (LUCA-i). Unatoč tome što je SGC najkonzerviranija informacija u biologiji, pitanje njegovoga porijekla do danas je nerazriješeno. U ovome radu izložene su vodeće teorije o evoluciji SGC: stereokemijska teorija koja postulira da je stereokemijski afinitet između kodona ili antikodona i pripadajuće aminokiseline uzrok njihovome pridruživanju; koevolucijska teorija koja kaže da je kod prvotno raspolagao s malim brojem aminokiselina prisutnih u okolišu, nakon čega su ostale kasnije dobivene metaboličkim putevima iz potonjih i zatim uključene u kod pri čemu su im pridruženi kodoni srodni onima njihovih prekursora; teorija minimizacije greške koja tvrdi da je otpornost stanice na mutacije i pogreške u translaciji bila predvodeći selekcijski pritisak koji je gurao evoluciju SGC. Svaki od spomenutih pristupa ima u obliku u kojemu su najčešće izloženi mane koje se čine nepremostivima te se budućnost istraživanja porijekla SGC vjerojatno nalazi u integriranom eksperimentalnom pristupu koji u obzir uzima sve od spomenutih faktora, a i evoluciju aaRS i ostatka translacijske mašinerije, kao relevantne u ranoj evoluciji i porijeklu SGC.The standard genetic code (SGC) is a code by which sequences of nucleotides are translated into sequences of amino acids such that each nucleotide triplet (sequence of three) called a codon is assigned to any one of 20 biological amino acids. The SGC is nearly universal in all extant life forms, which is why we can safely presume it had been established as such at least as far back as the last universal common ancestor (LUCA). Although the SGC is perhaps the greatest information constant in all of biology, the question of its origin remains unanswered. In this paper, main theories of its evolution and origin are demonstrated: the stereochemical theory, which hypothesizes that a stereochemical affinity was the driving force of adjoining codons to their cognate amino acids; the coevolution theory which posits that the code originally had fewer amino acids at its disposal, and the rest of the 20 were derived from this original set via assorted metabolic pathways, after which codons that previously had belonged to their precursors were assigned to them; the error minimization theory which says that the pressure to resist the deleterious effects of mutations and translation errors was the main selective pressure to drive SGC evolution. Each of the described theories or the approaches by which they are tested have their flaws, so the future of research on the origin and evolution of the SGC appears to be in an integrated approach which takes into account all of the above, as well as the evolution of the translation apparatus, as relevant in the early evolution of the SGC

The origin of the genetic code

Standardni genetički kod (SGC) je šifra prevođenja sekvence nukleotida u sekvencu aminokiselina na način da je svaki od mogućih tripleta (nizova od 3) nukleotida – kodon pridružen nekoj od 20 bioloških aminokiselina. SGC je gotovo univerzalan u živom svijetu, zbog čega znamo da je kao takav postojao i u posljednjem univerzalnom zajedničkom pretku (LUCA-i). Unatoč tome što je SGC najkonzerviranija informacija u biologiji, pitanje njegovoga porijekla do danas je nerazriješeno. U ovome radu izložene su vodeće teorije o evoluciji SGC: stereokemijska teorija koja postulira da je stereokemijski afinitet između kodona ili antikodona i pripadajuće aminokiseline uzrok njihovome pridruživanju; koevolucijska teorija koja kaže da je kod prvotno raspolagao s malim brojem aminokiselina prisutnih u okolišu, nakon čega su ostale kasnije dobivene metaboličkim putevima iz potonjih i zatim uključene u kod pri čemu su im pridruženi kodoni srodni onima njihovih prekursora; teorija minimizacije greške koja tvrdi da je otpornost stanice na mutacije i pogreške u translaciji bila predvodeći selekcijski pritisak koji je gurao evoluciju SGC. Svaki od spomenutih pristupa ima u obliku u kojemu su najčešće izloženi mane koje se čine nepremostivima te se budućnost istraživanja porijekla SGC vjerojatno nalazi u integriranom eksperimentalnom pristupu koji u obzir uzima sve od spomenutih faktora, a i evoluciju aaRS i ostatka translacijske mašinerije, kao relevantne u ranoj evoluciji i porijeklu SGC.The standard genetic code (SGC) is a code by which sequences of nucleotides are translated into sequences of amino acids such that each nucleotide triplet (sequence of three) called a codon is assigned to any one of 20 biological amino acids. The SGC is nearly universal in all extant life forms, which is why we can safely presume it had been established as such at least as far back as the last universal common ancestor (LUCA). Although the SGC is perhaps the greatest information constant in all of biology, the question of its origin remains unanswered. In this paper, main theories of its evolution and origin are demonstrated: the stereochemical theory, which hypothesizes that a stereochemical affinity was the driving force of adjoining codons to their cognate amino acids; the coevolution theory which posits that the code originally had fewer amino acids at its disposal, and the rest of the 20 were derived from this original set via assorted metabolic pathways, after which codons that previously had belonged to their precursors were assigned to them; the error minimization theory which says that the pressure to resist the deleterious effects of mutations and translation errors was the main selective pressure to drive SGC evolution. Each of the described theories or the approaches by which they are tested have their flaws, so the future of research on the origin and evolution of the SGC appears to be in an integrated approach which takes into account all of the above, as well as the evolution of the translation apparatus, as relevant in the early evolution of the SGC

Assessing the robustness of genetic codes and genomes

Deux approches principales existent pour évaluer la robustesse des codes génétiques et des séquences de codage. L'approche statistique est basée sur des estimations empiriques de probabilité calculées à partir d'échantillons aléatoires de permutations représentant les affectations d'acides aminés aux codons, alors que l'approche basée sur l'optimisation repose sur le pourcentage d’optimisation, généralement calculé en utilisant des métaheuristiques. Nous proposons une méthode basée sur les deux premiers moments de la distribution des valeurs de robustesse pour tous les codes génétiques possibles. En se basant sur une instance polynomiale du Problème d'Affectation Quadratique, nous proposons un algorithme vorace exact pour trouver la valeur minimale de la robustesse génomique. Pour réduire le nombre d'opérations de calcul des scores et de la borne supérieure de Cantelli, nous avons développé des méthodes basées sur la structure de voisinage du code génétique et sur la comparaison par paires des codes génétiques, entre autres. Pour calculer la robustesse des codes génétiques naturels et des génomes procaryotes, nous avons choisi 23 codes génétiques naturels, 235 propriétés d'acides aminés, ainsi que 324 procaryotes thermophiles et 418 procaryotes non thermophiles. Parmi nos résultats, nous avons constaté que bien que le code génétique standard soit plus robuste que la plupart des codes génétiques, certains codes génétiques mitochondriaux et nucléaires sont plus robustes que le code standard aux troisièmes et premières positions des codons, respectivement. Nous avons observé que l'utilisation des codons synonymes tend à être fortement optimisée pour amortir l'impact des changements d'une seule base, principalement chez les procaryotes thermophiles.There are two main approaches to assess the robustness of genetic codes and coding sequences. The statistical approach is based on empirical estimates of probabilities computed from random samples of permutations representing assignments of amino acids to codons, whereas, the optimization-based approach relies on the optimization percentage frequently computed by using metaheuristics. We propose a method based on the first two moments of the distribution of robustness values for all possible genetic codes. Based on a polynomially solvable instance of the Quadratic Assignment Problem, we propose also an exact greedy algorithm to find the minimum value of the genome robustness. To reduce the number of operations for computing the scores and Cantelli’s upper bound, we developed methods based on the genetic code neighborhood structure and pairwise comparisons between genetic codes, among others. For assessing the robustness of natural genetic codes and genomes, we have chosen 23 natural genetic codes, 235 amino acid properties, as well as 324 thermophilic and 418 non-thermophilic prokaryotes. Among our results, we found that although the standard genetic code is more robust than most genetic codes, some mitochondrial and nuclear genetic codes are more robust than the standard code at the third and first codon positions, respectively. We also observed that the synonymous codon usage tends to be highly optimized to buffer the impact of single-base changes, mainly, in thermophilic prokaryotes