Response GC-Biased Mutation Pressure and ORF Lengthening

Abstract

Xia et al. (2003) discuss whether the lengths of exons in eukaryotes and of genes in prokaryotes vary and whether they do so in relation to base composition (G+C content). In the paper which generated this debate, Oliver and Marı ´ n (1996) suggested that, given the compositional AT bias of standard stop codons (TAA, TAG, and TGA), a differential density of these termination signals is expected in random DNA sequences of different base composition, and therefore the expected length of reading frames (sequence segments of sense codons flanked by inphase stop codons) is a function of GC content. In other words, in GC-poor random sequences, the stop-codon density is expected to be higher than in GC-rich ones, and therefore the higher the GC content, the longer the expected reading frames. Empirical support for the model was sought by analyzing a sample of prokaryotic genes and a sample of eukaryotic exon data (Oliver and Marı ´ n 1996). With the model, the expected distribution of open reading frame (ORF) lengths in any random sequence with a given base composition can be computed; by comparing true ORF lengths to such random expectations, evolutionary forces involved in ORF lengthening can then be identified. Such comparisons can also be used for accurately predicting the coding content in anonymous sequences (Carpena et al. 2002). Correspondence to: Jose ´ L. Oliver