Genome Organization & Evolution

Chromosomes

• Genes are always in genomic structures (chromosomes) – never ‘free floating’

• Bacterial genomes are circular

• Eukaryotic genomes are oriented strands

• Question: why are chromosomes?

Size of genomes

Epstein-Barr virus 0.172 x 106

E. coli 4.6 x 106

S. cerevisiae 12.1 x 106

C. elegans 95.5 x 106

A. thaliana 117 x 106

D. melanogaster 180 x 106

H. sapiens 3200 x 106

Genomic structures

• Chromosomes

• Plasmids

• Mitochondria

• Chloroplasts

Competition & cooperation

• Are genes ‘selfish’? Examples?

• Are genes ‘cooperative’? Examples?

• Which came first, cooperation or competition?

• How do cooperation and competition evolve?

Gene structure

• Exons (coding regions)• Introns

– Who has ’em?– What size?– Which is original form?

• Computational challenges & clues– Find the exon/intron structure– Use the function to facilitatie location

Regulatory mechanisms

• ‘organize expression of genes’ (function calls)

• Promoter region (binding site), usually near coding region

• Binding can block (inhibit) expression• Computational challenges

– Identify binding sites– Correlate sequence to expression

Proteins

• Most protein sequences (today) are inferred• What’s wrong with this?• Proteins (and nucleic acids) are modified• ‘mature’ Rna• Computational challenges

– Identify (possible) aspects of molecular life cycle

– Identify protein-protein and protein-nucleic acid interactions

Genetic variation

• Variable number tandem repeats (minisatellites). 10-100 bp. Forensic applications.

• Short tandem repeat polymorphisms (microsatellites). 2-5 bp, 10-30 consecutive copies.

• Single nucleotide polymorphisms

Single nucleotide polymorphisms

• 1/2000 bp.

• Types– Silent– Truncating – Shifting

• Significance: much of individual variation.

• Challenge: correlation to disease

Anatomy of a gene

• ORF. From start (ATG) to stop (TGA, TAA, TAG)

• Upstream region with binding site. (e.g. TATA box).

• Poly-a ‘tail’

• Splices. Bounded by AG and GT splice signals.

Yeast genome

• 4.6 x 106 bp. One chromosome. Published 1997.

• 4,285 protein-coding genes

• 122 structural RNA genes

• Repeats. Regulatory elements. Transposons.

• Lateral transfers.

Yeast protein functionsRegulatory 45 1.05%

Cell structure 182 4.24

Transposons,etc 87 2.03

Transport & binding 281 6.55

Putative transport 146 3.40

Replication, repair 115 2.68

Transcription 55 1.28

Translation 182 4.24

Enzymes 251 5.85

Unknown 1632 38.06

Eukaryotic genome

• Moderately repetitive– Functional (protein coding, tRNA coding)– Unknown function

• SINEs (short interspersed elements)– 200-300 bp

– 100,000 copies

• LINEs (long interspersed elements)– 1-5 kb

– 10-10,000 copies

Eukaryotic genome

• Highly repetitive– Minisatellites

• Repeats of 14-500 bp• 1-5 kb long• Scattered throughout genome

– Microsatellites• Repeats up to 13 bp• 100s of kb long, 106 copies• Around centromere

– Telomeres• Short repeats (6 bp)• 250-1,000 at ends of chromosomes

HW 3

• Due March 5

• Weblem 2.2, p 112

• Weblem 2.14, p 113