3-base periodicity in coding DNA is affected by intercodon dinucleotides.

Joaquín Sánchez

doi:10.6026/97320630006327

Abstract

All coding DNAs exhibit 3-base periodicity (TBP), which may be defined as the tendency of nucleotides and higher order n-tuples, e.g. trinucleotides (triplets), to be preferentially spaced by 3, 6, 9 etc, bases, and we have proposed an association between TBP and clustering of same-phase triplets. We here investigated if TBP was affected by intercodon dinucleotide tendencies and whether clustering of same-phase triplets was involved. Under constant protein sequence intercodon dinucleotide frequencies depend on the distribution of synonymous codons. So, possible effects were revealed by randomly exchanging synonymous codons without altering protein sequences to subsequently document changes in TBP via frequency distribution of distances (FDD) of DNA triplets. A tripartite positive correlation was found between intercodon dinucleotide frequencies, clustering of same-phase triplets and TBP. So, intercodon C|A (where "|" indicates the boundary between codons) was more frequent in native human DNA than in the codon-shuffled sequences; higher C|A frequency occurred along with more frequent clustering of C|AN triplets (where N jointly represents A, C, G and T) and with intense CAN TBP. The opposite was found for C|G, which was less frequent in native than in shuffled sequences; lower C|G frequency occurred together with reduced clustering of C|GN triplets and with less intense CGN TBP. We hence propose that intercodon dinucleotides affect TBP via same-phase triplet clustering. A possible biological relevance of our findings is briefly discussed.

Highlights

The 3-base periodicity (TBP) is an intrinsic property of all coding DNA [1,2,3,4,5,6] that is characterized by the disposition of nucleotides and higher order n-tuples, e.g. trinucleotides, so that they are preferentially separated by multiples of 3 bases, i.e. 3, 6, 9, 12 etc
We found differences between native and synonymous-codon-shuffled sequences in TBP as well as in clustering of samephase triplets; we propose that intercodon dinucleotides affect TBP via changes in same-phase triplet clustering
Intercodon dinucleotide frequencies in native and randomized sequences: We found higher intercodon T|G, C|A A|G and C|T frequencies in native sequences as compared to controls

Summary

Background

The 3-base periodicity (TBP) is an intrinsic property of all coding DNA [1,2,3,4,5,6] that is characterized by the disposition of nucleotides and higher order n-tuples, e.g. trinucleotides (triplets), so that they are preferentially separated by multiples of 3 bases, i.e. 3, 6, 9, 12 etc. At the protein level same-phase triplet clustering and TBP occur because in natural protein-coding sequences codons are never used in equal proportions; that is, the influence of protein is reduced to codon composition. This would explain why computer generated sequences with the same codon usage as native sequences expressed TBP [3] and why TBP persisted after shuffling of codons [9], differences in TBP were pointed out [9]. To investigate if and how intercodon dinucleotides affected TBP, we disrupted the natural distribution of synonymous codon by randomly shuffling them without changing protein sequences. We found differences between native and synonymous-codon-shuffled sequences in TBP as well as in clustering of samephase triplets; we propose that intercodon dinucleotides affect TBP via changes in same-phase triplet clustering. As in other cases the x-axis is presented in logarithmic form to help visualization and frequency values are shown in the y-axis

Discussion

Findings

Conclusion