  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.
