<P> They noted that 70% of the transcription coverage was less than 1 transcript per cell . They noted that this "larger proportion of genome with reproducible but low biochemical signal strength and less evolutionary conservation is challenging to parse between specific functions and biological noise". Furthermore, assay resolution often is much broader than the underlying functional sites so some of the reproducibly "biochemically active but selectively neutral" sequences are unlikely to serve critical functions, especially those with lower - level biochemical signal . To this they added, "However, we also acknowledge substantial limitations in our current detection of constraint, given that some human - specific functions are essential but not conserved and that disease - relevant regions need not be selectively constrained to be functional ." On the other hand, they argued that the 12--15% fraction of human DNA under functional constraint, as estimated by a variety of extrapolative evolutionary methods, may still be an underestimate . They concluded that in contrast to evolutionary and genetic evidence, biochemical data offer clues about both the molecular function served by underlying DNA elements and the cell types in which they act . Ultimately genetic, evolutionary, and biochemical approaches can all be used in a complementary way to identify regions that may be functional in human biology and disease . </P> <P> Some critics have argued that functionality can only be assessed in reference to an appropriate null hypothesis . In this case, the null hypothesis would be that these parts of the genome are non-functional and have properties, be it on the basis of conservation or biochemical activity, that would be expected of such regions based on our general understanding of molecular evolution and biochemistry . According to these critics, until a region in question has been shown to have additional features, beyond what is expected of the null hypothesis, it should provisionally be labelled as non-functional . </P> <P> Many noncoding DNA sequences must have some important biological function . This is indicated by comparative genomics studies that report highly conserved regions of noncoding DNA, sometimes on time - scales of hundreds of millions of years . This implies that these noncoding regions are under strong evolutionary pressure and positive selection . For example, in the genomes of humans and mice, which diverged from a common ancestor 65--75 million years ago, protein - coding DNA sequences account for only about 20% of conserved DNA, with the remaining 80% of conserved DNA represented in noncoding regions . Linkage mapping often identifies chromosomal regions associated with a disease with no evidence of functional coding variants of genes within the region, suggesting that disease - causing genetic variants lie in the noncoding DNA . The significance of noncoding DNA mutations in cancer was explored in April 2013 . </P> <P> Noncoding genetic polymorphisms play a role in infectious disease susceptibility, such as hepatitis C. Moreover, noncoding genetic polymorphisms contribute to susceptibility to Ewing sarcoma, an aggressive pediatric bone cancer . </P>

Why is the noncoding region of dna more variable than trait coding regions of dna