THE PROBABILITY OF OCCURRENCE OF OLIGOMER MOTIFS IN THE HUMAN GENOME AND GENOMIC MICROHETEROGENEITY

A previously published method for predicting the frequency of random o ccurrence of a completely specified DNA oligomer in a longer sequence dataset has been generalized to allow degeneracy in the oligomer seque nce. With this enhancement, several datasets consisting of sequences f rom the human genome were searched for the occurrence of consensus bin ding sites for a set of 13 transcription factors. Although because of the biological significance of these sequences one might predict that they would occur more often than the random frequency, many of the con sensus oligomers were found at lower than expected frequencies. Severa l (G+C)-rich oligomers were found to be moderately over-represented, b ut this could be accounted for, in part, by the occurrence of (G + C)- rich tracts in the human sequences. Regions very high in (G + C) were found to occur at much higher frequencies than expected in the human g enome, and this severely limits the usefulness of this approach for pr edicting the frequency of(G + C)-rich oligomers. Unexpectedly, more th an 1% of the human genome consists of tracts at least 28 bp in length with a (G + C) content greater than 85%. (C) 1996 Academic Press Limit ed