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 virus0.172 x 10 6 E. coli4.6 x 10 6 S. cerevisiae12.1 x 10 6 C. elegans95.5 x 10 6 A. thaliana117 x 10 6 D. melanogaster180 x 10 6 H. sapiens3200 x 10 6

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) bp. Forensic applications. Short tandem repeat polymorphisms (microsatellites). 2-5 bp, consecutive copies. 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 10 6 bp. One chromosome. Published ,285 protein-coding genes 122 structural RNA genes Repeats. Regulatory elements. Transposons. Lateral transfers.

Yeast protein functions Regulatory451.05% Cell structure Transposons,etc Transport & binding Putative transport Replication, repair Transcription Translation Enzymes Unknown

Eukaryotic genome Moderately repetitive –Functional (protein coding, tRNA coding) –Unknown function SINEs (short interspersed elements) – bp –100,000 copies LINEs (long interspersed elements) –1-5 kb –10-10,000 copies

Eukaryotic genome Highly repetitive –Minisatellites Repeats of bp 1-5 kb long Scattered throughout genome –Microsatellites Repeats up to 13 bp 100s of kb long, 10 6 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