Australasian Microarray & Associated Technologies Association, AMATA

Mattick, J - Institute for Molecular Bioscience
University of Queensland, 306 Carmody Road, St Lucia, Brisbane, QLD 4072, Australia

It appears that the genetic programming of mammals and other complex organisms has been misunderstood for the past 50 years, because of the assumption - largely true in prokaryotes, but not in complex eukaryotes - that most genetic information is transacted by proteins. The numbers of protein-coding genes do not change appreciably across the metazoa, whereas the relative proportion of non-protein-coding sequences increases markedly with increased developmental complexity. Moreover, it is now evident that the majority of the mammalian genome is transcribed in a developmentally regulated manner, and that most complex genetic phenomena in eukaryotes are RNA-directed. Evidence will be presented that (i) regulatory information scales quadratically with functional complexity; (ii) current estimates of the amount of the human genome under evolutionary selection are simplistic and probably based on a false premise; (iii) there are thousands of non-protein-coding transcripts in mammals that are dynamically expressed during differentiation and development, many of which show precise expression patterns and subcellular localization in the brain; (iv) many 3’UTRs are expressed separately from their associated protein-coding sequences to transmit genetic information in trans; and (v) there are large numbers of small RNAs, including new classes, expressed from the human and mouse genomes, that may be discerned in deep sequencing datasets. There is also genome-wide evidence of editing of noncoding RNA sequences, especially in the brain and especially in humans (in Alu elements), which may form an important part of the molecular basis of learning and memory. Thus the majority of the human genome appears not to be junk but rather is devoted to a highly sophisticated RNA regulatory system that directs developmental trajectories and mediates gene-environment interactions via the control of chromatin architecture and epigenetic memory, transcription, splicing, RNA modification and editing, mRNA translation and RNA stability.