Chargaffs Legacy.pdf - Biology

132D.R. Forsdyke, J.R. Mortimer / Gene 261 (2000) 127±1375. The GC ruleWe propose above that in some circumstances evolutionaryselective pressures have acted to preserve nucleic acidsecondary structure, sometimes at the expense of anencoded protein. That this might also apply to the speciesdependentcomponent of the base composition, (C 1 G)%,arose from Naboru Sueoka's demonstration in 1961, beforethe genetic code was deciphered, that the amino acidcomposition of the proteins of microorganisms is in¯uenced,not just by the demands of the environment on theproteins, but also by the base composition of the genomeencoding those proteins. The observation has since beenabundantly con®rmed in a wide variety of animal andplant species (Lobry, 1997).Sueoka (1961) further pointed out that for individual`strains' of Tetrahymena the (C 1 G)% (referred to as`GC') tends to be uniform throughout the genome:ªIf one compares the distribution of DNA moleculesof Tetrahymena strains of different mean GC contents,it is clear that the difference in mean values is due to arather uniform difference of GC content in individualmolecules. In other words, assuming that strains ofTetrahymena have a common phylogenetic origin,when the GC content of DNA of a particular strainchanges, all the molecules undergo increases ordecreases of GC pairs in similar amounts. This resultis consistent with the idea that the base composition israther uniform not only among DNA molecules of anorganism, but also with respect to different parts of agiven molecule.ºAgain, this observation has been abundantly con®rmedfor a wide variety of species (Muto and Osawa, 1987),although many organisms considered higher on the evolutionaryscale have their genomes sectored into regions oflow or high (C 1 G)% (Bernardi and Bernardi, 1986;Bernardi, 2000; see Section 9).Sueoka (1961) also noted a link between (C 1 G)% andreproductive isolation for strains of Tetrahymena:ªDNA base composition is a re¯ection of phylogeneticrelationship. Furthermore, it is evident thatthose strains which mate with one another (i.e. strainswithin the same `variety') have similar base compositions.Thus strains of variety 1 ¼, which are freelyintercrossed, have similar mean GC content.ºWhen the genetic code was deciphered in the early 1960s,it was observed that there are more codons than amino acids,so that most amino acids can correspond to more than onetriplet codon. This gives some ¯exibility to a nucleic acidsequence. Sometimes an amino acid can be encoded fromamong as many as six possible synonymous codons. WalterFitch (1974) noted that `the degeneracy of the genetic codeprovides an enormous plasticity to achieve secondary structurewithout sacri®cing speci®city of the message'. Yet, asoutlined above, sometimes even this `plasticity' is insuf®cient,so that, with the exception of genes under positiveDarwinian selection (Forsdyke, 1995b, 1996a), genomicsecondary structure (`fold pressure') and (C 1 G)% `callthe tune'. Non-synonymous codon changes modify theamino acid sequence, sometimes at the expense of proteinstructure and function. A protein has to adapt to thedemands of the environment, but it also has to adapt togenomic forces which we will show have derived, notfrom the conventional environment acting upon the convention(`classical') phenotype, but from what we call the`reproductive environment' acting on the `genome phenotype'',or `reprotype'. Thus Bernardi and Bernardi noted in1986 that:ªThe organismal phenotype comprises two components,the classical phenotype, corresponding to the`gene products', and a `genome phenotype' which isde®ned by [base] compositional constraints.º6. Codon choiceThe issue of which codon was employed in a particularcircumstance was considered by Richard Grantham, whonoted in 1972 that codon choice was not random in microorganisms,`suggesting a mechanism against [base] compositiondrift'. Observing that `little latitude appears left for`neutral' or synonymous mutations in coliphage codons', hewas led to his `genome hypothesis', which speci®ed thatunde®ned adaptive genomic pressure(s) caused changes inbase composition and hence in codon choice (Grantham etal., 1986):ªEach ¼species has a `system' or coding strategy forchoosing among synonymous codons. This system ordialect is repeated in each gene of a genome and henceis a characteristic of the genome.ºThere was also a sense that the coding strategy was ofrelevance to the most fundamental aspects of an organism'sbiology:ªWhat is the fundamental explanation for interspeci®cvariation in coding strategy? Are we faced with asituation of continuous variation within and betweenspecies, thus embracing a Darwinian perspective ofgradual separation of populations to form new species¼? This is the heart of the problem of molecularevolution.ºGrantham and his colleagues further pointed to the needto determine `how much independence exists between the