Today Building a genome –Nucleotides, GC content and isochores –Gene structure and expression; introns –Evolution of noncoding RNAs Evolution of transcription –Transcription & Translation –Recoding and RNA editing –Evolution of the genetic code
The four nucleotides of DNA
Watson & Crick actually got it wrong …
GC content versus optimal growth temperature Genome-wide Ribosomal RNAs
Environmental signature on GC content
Structure of human isochores
Lack of isochores in lizards
GC-content correlates with recombination rate
A B C { AAAAAA { Influences gene from afar…. D E F G GH { A._______________ B. _______________ C. _______________ D. _______________ E. _______________ F. _______________ G. _______________ H. _______________ I. _______________ I I Anatomy of a eukaryotic gene
Introns cleaved out by the spliceosome
Phylogenetic distribution of introns implies recent origin
Intron phase and size
Rotem Sorek et al. Genome Res. 2003; 13: Figure 3 Human-mouse alignment of the KCND3 gene, corresponding to RefSeq NM_ (from VISTA browser, Intronic regions adjacent to exons are often conserved
2005: Widespread transcription in the human genome revealed by microarray analysis
Fast forward 2010: Expression tracks known genes closely
Number of regulatory genes (R) vs. total number of genes (G) Circles - Bacteria; triangles - Archaea R = G 2 Mycoplasma genitalium Bradyrhizobium japonicum
Does ‘noncoding DNA’ increase genomic complexity?
Was eukaryotic complexity released by noncoding RNAs?
MicroRNAs - a new class of small RNAs with big roles in development and evolution
Translational repression by microRNAs
microRNAs as cladistic characters
Explosive diversity of cichlid fish
Rapid evolution of microRNA targets – a link with speciation?
The ‘universal’ genetic code
Translation
Phe 12s rRNA Val 16s rRNA Leu Ile Gln Met Trp Ala Asn Cys Tyr COI Ser Asp COII Lys ATP8 ATP6 COIII Gly NADH3 Arg NADH4L NADH4 His Ser Leu NADH5 Cyt b Thr Control Region Pro NADH6 Glu noncoding Structure of vertebrate mitochondrial DNA (~17,000 bp) rRNA genes tRNA genes ATP synthase genes Cytochrome bc1 complex Cytochrome Oxidase NADH:Ubiquinone Oxidoreductase NADH1 NADH2
Four ways to change the coding of amino acids from RNA
Wobble rules in various organisms base modifications in tRNAs can increase decoding breadth
A code that minimizes polarity changes better than the universal code