Genome-wide functional analysis of human 5' untranslated region introns

We performed a genome-scale computational analysis of 5'UTR introns in humans. We discovered that the most highly expressed genes tended to have short 5'UTR introns rather than having long 5'UTR introns or lacking 5'UTR introns entirely. Although we found no correlation in 5'UTR intron presence or length with variance in expression across tissues, which might have indicated a broad role in expression-regulation, we observed an uneven distribution of 5'UTR introns amongst genes in specific functional categories. In particular, genes with regulatory roles were surprisingly enriched in having 5'UTR introns. Finally, we analyzed the evolution of 5'UTR introns in non-receptor protein tyrosine kinases (NRTK), and identified a conserved DNA motif enriched within the 5'UTR introns of human NRTKs.Our results suggest that human 5'UTR introns enhance the expression of some genes in a length-dependent manner. While many 5'UTR introns are likely to be evolving neutrally, their relationship with gene expression and overrepresentation among regulatory genes, taken together, suggest that complex evolutionary forces are acting on this distinct class of introns.The advent, evolution and functional significance of introns in eukaryotes have been topics of intense debate over the past 30 years (reviewed in [1,2]). There are two major opposing views on when introns arose in evolution; this 'introns-early' versus 'introns-late' controversy is reviewed in [1,2]. Also, debate exists on what causes their frequent losses and gains [3,4] and whether they have any adaptive significance.Neutral or nearly neutral population genetic processes under general, non-adaptive conditions have been suggested to result in dynamic gains and losses of introns. Such neutral processes could account for some of the observed patterns of intron presence [5], but do not rule out the possibility that adaptive processes are simultaneously contributing to the maintenance of some introns. Introns have been suggested