UQ eSpace

Abstract

Protein-coding genes in eukaryotes occupy a small fraction of the genome and are interrupted by non-protein-coding introns as well as separated by large intergenic regions. Although it is recognised that there is important ds-regulatory information in these regions, the majority is generally regarded as non-functional. However, given the fact that much of these noncoding regions are transcribed, it has been proposed that the RNA derived from introns and intergenic regions represents an additional layer of regulation in eukaryotic genomes and therefore that much of the genome of complex organisms is functional. I measured the extent of transcription of coding and noncoding sequences of metazoan genomes counting the full length of primary transcripts (genomic length of exons and introns) of known genes, annotated “mRNAs”, and spliced ESTs. I found that approximately 60% of the genomes of the nematode, fruit fly, mouse and human are transcribed. The actual numbers and amounts of protein-coding sequences remain relatively constant, whereas both the fraction and the amount of non-protein-coding transcription increases dramatically with developmental complexity, rising from 30-50 Mb in invertebrates to 1.3-1.6 Gb in mouse and human respectively, over 800 Mb of which is non-repetitive sequence. There is good reason to expect that alternative splicing may be controlled by trans-acting regulatory RNAs since this process is not easily explained by protein regulators and it is known that antisense RNAs can alter splice patterns. If alternative splicing is controlled by RNA one would predict that alternative splice sites should be more highly conserved than constitutive splice sites. I therefore examined the degree of sequence conservation and showed that coding and noncoding sequences are more highly conserved around alternative splice sites than constitutive ones, with some unusual examples having very long identical regions. Surprisingly, some sequences are identical even between humans and fish, species separated by vast evolutionary distances.