Di-nucleotide Entropy as a Measure of Genomic Sequence Functionality
  Considering vast amounts of genomic sequences of mostly unknown functionality, in-silico prediction of functional regions is an important enterprise. Many genomic browsers employ GC content, which was observed to be elevated in gene-rich functional regions. This report shows that the entropy of di- and tri-nucleotides distributions provides a superior measure of genomic sequence functionality, and proposes an explanation on why the GC content must be elevated (closer to 50%) in functional regions. Regions with high entropy strongly co-localize with exons and provide genome-wide evidences of purifying selection acting on non-coding regions, such as decreased SNPs density. The observations suggest that functional non-coding regions are optimised for mutation load in a way, that transition mutations have less impact on functionality than transversions, leading to the decrease in transversions to transitions ratio in functional regions. 
Dmitri Parkhomchuk