Highly prevalent putative quadruplex sequence motifs in human DNA

Abstract

We report here the results of a systematic search for the existence and prevalence of potential intramolecular G-quadruplex forming sequences in the human genome. We have also examined the tendency for particular sequences of 'loop' regions to occur in particular positions with respect to the G-tracts in a quadruplex. Using arithmetic ratio and probability techniques we have discovered frequent and systematic occurrence of certain sequence types, the most prominent being a potential quadruplex containing CCTGT in the first 'loop' position. Being able to highlight types of potential quadruplex sequences in G-rich regions is an important step in searching for biologically relevant sequences and finding their function.

Figure 1

Ways in which quadruplex-fold ambiguity can occur. (a) Shaded regions represent the guanines contributing to the G-quartets and the unshaded regions the loops. Regions of high guanine density tend to have more quadruplex hits which in some cases lead to many hits for a single region of DNA. (b) Overlapping quadruplexes. In the first (un-restricted) dataset, the above sequence would produce five possible quadruplex folds, and in the second (arbitrary) dataset, this sequence would only have been counted as two distinct quadruplexes.

Figure 2

Consensus sequences for (a) CCTGTCA and (b) CCTGTT sequence types. Diagrams were generated with the program MakeLogo (33). A total of 1956 sequences were used to find the consensus sequence for CCTGTCA and 2361 sequences for the CCTGTT type. The height of each letter is proportional to the number of times each base appeared in that position.