ABSTRACT
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When genomes are sequenced, the information is immediately usable for bioinformatics, microarrays, and many other applications. Genomes can be compared and genes manipulated knowing only the DNA sequence. The function of DNA and the one-way translation of data were rarely in question. From this simple understanding the signifi cance of the proteome rose to astonishing prominence and became the research objective of many with goals and dreams, “. . . capable of identifying up to 1 million proteins a day. . . .”1 But much has changed over the last few years; histone tails are modifi ed by acetylation, phosphorylation, and methylation, all affecting the
local chromatin structure and transcriptional regulation of adjacent genes.2 Micro RNAs (about 22 nucleotides in length) add further complexity, producing transcripts that form imperfect hairpin structures and guide RNA silencing.3,4 Alternative premRNA splicing is another mechanism for regulating gene expression in higher eukaryotes. Recent estimates indicate 30% of the primary transcripts of the human genome are subject to alternative splicing showing specifi c spatial/temporal patterns during normal development. In complex genes, alternative splicing generates dozens or even hundreds of different mRNA isoforms from a single transcript. It has been argued that nonprotein coding RNA,5 including microRNAs, siRNAs, and intronic RNA, are part of a vast regulatory mechanism, and phenotypic variations between species (and individuals) results from differences in the control architecture, not the proteins themselves.
