Genes and Genomes

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• Genes and Genomes

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Francis Collins, HGP
Craig Venter, Celera Inc.
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Hierarchical vs. Whole Genome Shotgun
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Raw Genome Data
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Sequences complete
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How many genes?
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Celera says that there are only 30,000 genes

• Affymetrix 60,000 human genes on GeneChips?
• Incyte over 120,000 genes?
• GenBank 49,000 gene coding sequences?
• UniGene gt 89,000 clusters of unique ESTs?

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What are genes?
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Eukaryotic Genomes
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Eukaryotic Genes
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Dogmas
One Gene One Protein
Predates the description of the chemical
structure of DNA by Watson and Crick 1953 and
even the identification of DNA as the molecule of
inheritance.
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A Dynamic Concept

• Introns/exons
• Postransriptional modifications
• Alternative splicing
• Differential expression
• Genes-in-genes
• Genes-ad-genes
• Postranslational modifications
• Multi-subunit proteins

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Current consensus

• 15,000 known genes (similarity to previously
  isolated genes and expressed sequences from a
  large variety of different organisms)
• 17,000 predicted (GenScan, GeneFinder, GRAIL)
• Based on and limited to previous knowledge

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Sources of Complexity

• Gene number (2-3 fold over worm and fly)
• Alternative splicing (ca. 3 transcripts per gene
  vs. 1.3 for worm)
• Different organization (domains, subunits)
• New architecture (CNS, brain complexity)
• New abilities (Cognitive abilities)

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Challenge Opportunity

• To locate all of the genes in the human genome
  and describe their functions may take another
  15-20 years!

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Whats the trouble?

• 1-3 coding sequences
• large number and long stretches of repetitions
• pseudogenes
• highly specific, rarely expressed genes
• paralogous genes
• regulatory regions
• short RNAs
• first and last exons
• splice variations

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What does it mean?

• 30,000 - 35,000 genes
• Average coding length 1.4 kb
• Average gene extent 30 kb
• Average gene density 11.5/1 Mb
• Y chromosome 6.4/1 Mb
• Chromosome 19 26.8/1 b

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Raw Genome Data
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Its all about patterns

• Promoters
• Open reading frames (ORF)
• Transcriptional and translational start and stop
  sites/codons
• Intron splice sites
• Enhancer signals
• Poly-A insertion sites

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