Genome projects and model organisms

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Genome projects and model organisms

• Level 3 Molecular Evolution and Bioinformatics
• Jim Provan

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Genome projects and model organisms
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Genome projects

• Completed genomes
• Eubacteria (inc. Escherichia coli, Bacillis
  subtilis, Haemophilus influenzae, Synechocystis
  PCC6803)
• Archaea (inc. Methanococcus jannaschii,
  Methanobacterium thermoautotrophium)
• Eukarya
• Saccharomyces cerevisiae
• Caenorhabditis elegans
• Homo sapiens
• Arabidopsis thaliana
• Partially sequenced genomes e.g. Drosophila
  melanogaster, Fugu rubripes, Oryza sativa

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Relationships between model organisms
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Eubacterial genomes Bacillus subtilis

• Genome 4,214,810 bp
• 4100 protein sequences
• Average gene 890 bp
• Density 1 gene / 1028 bp
• 89 of total genome is protein-coding
• Protein coding genes
• 53 single copy
• 47 paralogous gene families
• Mostly involved in transport
• Genes are proximal i.e. have evolved through
  tandem duplication of single genes

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Eubacterial genomes Bacillus subtilis

• On the basis of homology with genes of known
  function, 58 of B. subtilis genes could be
  assigned to functional categories
• The B. subtilis genome contains remnants of 10
  prophages, suggesting that horizontal transfer
  has played a significant role in evolution of the
  genome
• Orthologous counterparts in other bacteria
• 1000 genes (24) have counterparts in E. coli
  (Gram -ve)
• More significantly, 100 operons conserved as
  well
• 800 genes (20) have orthologues in
  Synechocystis PCC6803 (Cyanobacterium)

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Eubacterial genomes Mycoplasmas

• Obligate parasites
• Thought to be derived from Gram ve bacteria
  similar to B. subtilis
• 312 genes of M. genitalium (66) have homologues
  in Gram ve bacteria
• Parasitic lifestyle has led to a dramatic
  reduction in genome size and content
• Smallest-known genome in a self-replicating
  organism

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Eubacterial genomes Mycoplasmas

• M. genitalium genome
• Circular chromosome of 580,070 bp
• Only 470 predicted genes for DNA replication,
  transcription and translation, DNA repair,
  cellular transport and energy metabolism
• Coding regions comprise 88 of the genome
• Similar to H. influenzae (85)
• Suggests that genome reduction has been due to
  loss of genes and not reduction in gene size or
  increase in gene density
• M. pneumoniae genome
• Larger than M. genitalium (816 kbp)
• All M. genitalium genes found in M. pneumoniae
• Not simply truncated - evidence of genome
  rearrangements

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Eubacterial genomes E. coli

• 4288 protein coding genes
• Average ORF 317 amino acids
• Very compact average distance between genes
  118bp
• Numerous paralogous gene families 38 45 of
  genes arisen through duplication
• Homologues
• H. influenzae (1130 of 1703)
• Synechocystis (675 of 3168)
• M. jannaschii (231 of 1738)
• S. cerevisiae (254 of 5885)

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The minimum genome and redundancy

• Minimum set of genes required for survival
• Replication and transcription
• Translation (rRNA, ribosomal proteins, tRNAs
  etc.)
• Transport proteins to derive nutrients
• ATP synthesis
• Entire pathways eliminated in Mycoplasma
• Amino acid biosynthesis (1 gene vs. 68 in H.
  influenzae)
• Metabolism (44 genes vs. 228 in H. influenzae)
• Comparison of M. genitalium and H. influenzae has
  identified a minimum set of 256 genes

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Archaeal genomes M. jannaschii

• Requires no organic nutrients for growth has all
  biochemical pathways to use inorganic
  constituents
• Only 38 of genes could be assigned a known
  function
• Genes for translation, transcription and DNA
  replication similar to eukaryote genes
• DNA polymerase
• Ribosomal proteins
• Translation initiation factors

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Fungal genomes S. cerevisiae

• First completely sequenced eukaryote genome
• Very compact genome
• Short intergenic regions
• Scarcity of introns
• Lack of repetitive sequences
• Strong evidence of duplication
• Chromosome segments
• Single genes
• Redundancy non-essential genes provide selective
  advantage

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Plant genomes Arabidopsis thaliana

• Contains 25,498 genes from 11,000 families
• Cross-phylum matches
• Vertebrates 12
• Bacteria / Archaea 10
• Fungi 8
• 60 ESTs have no match in non-plant databases
• Evolution involved whole genome duplication
  followed by subsequent gene loss and extensive
  local gene duplications

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Invertebrate genomes C. elegans

• Genome even less compact than yeast
• One gene every 7143 bp (2155 bp in yeast)
• Due mainly to introns in protein coding genes
• Much more compact than humans (One gene every
  50,000 bp)
• Compactness due mainly to polycistronic
  arrangement
• Trans-splicing
• Co-expression and co-regulation

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Vertebrate genomes Fugu rubripes

• Pufferfish genome (400 Mb) only four times larger
  than C. elegans and 7.5 times smaller than human
  genome
• Homologous genes in Fugu and mammals show
  conserved synteny
• Same exon-intron organisation
• Introns much smaller
• Useful for identifying conserved essential
  elements in vertebrate genomes

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The genome of the cenancestor

• Availability of complete genome sequences from
  the three domains of life creates an opportunity
  for the reconstruction of the complete genome of
  the common ancestor
• Of minimal bacterial set (256 genes), 143 have
  orthologues in yeast (eukaryote)
• Universal translation apparatus suggests that
  cenancestor had a fully developed translation
  system
• Extreme differences in DNA replication apparatus
• Many fundamental metabolic processes are carried
  out by similar proteins in Archaea and
  eubacteria
• Suggests a universal, autotrophic ancestor
• Not all central metabolism is universal
  (methanogenesis, photosynthesis etc.)