A New Understanding of the Human Genome
It appears that the genetic programming of humans 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 are relatively constant and largely orthologus across the metazoa, whereas the relative proportion of non-protein-coding sequences increases with increasing developmental complexity. Moreover, while only a tiny fraction encodes proteins,it is now evident that the majority of the mammalian genome is transcribed, and that most complex genetic phenomena in eukaryotes are RNA-directed. Evidence will be presented that(ⅰ) regulatory information scales quadratically with functional and developmental complexity;(ⅱ) 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; (ⅲ) there are large numbers of small RNAs,including new classes, that may be discerned from bioinformatic analysis of genomic and deep sequencing transcriptomic datasets; and (ⅳ) much, if not most, of the mammalian genome may not be evolving neutrally, but rather is composed of different types of sequences (includ-ing transposon-derived sequences) that are evolving at different rates under different selection pressures and different structure-function constraints. There is also genome-wide evidence of RNA editing, especially in the human brain, which may constitute a key molecular pathway underpinning learning and cognition. These and other observations suggest that the majority of the human genome specifies a 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.
John Mattick
Institute for Molecular Bioscience, University of Queensland, Brisbane
国际会议
The 7th Asia-Pacific Bioinformatics Conference(第七届亚太生物信息学大会)
北京
英文
9
2009-01-01（万方平台首次上网日期，不代表论文的发表时间）