Today Building a genome –Nucleotides, GC content and isochores –Gene structure and expression; introns –Evolution of noncoding RNAs Evolution of transcription.

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

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B

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Influences gene from afar….

D

EF G

GH

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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: 1631-1637

Figure 3 Human-mouse alignment of the KCND3 gene, corresponding to RefSeq NM_004980 (from VISTA browser, http://pipeline.lbl.gov/vistabrowser/)

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 = 0.00002G2

Mycoplasmagenitalium

Bradyrhizobiumjaponicum

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 rRNAVal

16s rRNA

LeuIle

Gln

Met

Trp

Ala

Asn

Cys

Tyr

COI

SerAspCOII

LysATP8

ATP6COIII

GlyNADH3

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