BiolChem 473

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Biol/Chem 473
Schulze lecture 1 Eukaryotic genomes
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What I do

• Ph.D. in Genetics and Molecular Biology
• Ph.D. project studied heterochromatic genes
  (active genes located in repressive parts of the
  genome) in Drosophila, which involved an analysis
  of chromatin structure
• Post-doctoral and present research study the
  role nuclear organization plays in regulating
  genome architecture and gene expression, using
  Drosophila as a model organism

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Prokaryotes and Eukaryotes
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Prokaryotic vs eukaryotic cells
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Prokaryotic vs. eukaryotic cell size
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Prokaryotic vs. eukaryotic genomes
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Prokaryotic vs. eukaryotic genome organization

• Bacterial genome is oganized into a single
  (usually) circular chromosome that is relatively
  small (106bp)

• Eukaryotic genome is arranged in a series of
  linear chromosomes that vary widely in size

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Prokaryotic genomes are very economically
organized!
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Lower eukaryotic genomes tend to be
economically organized too.
Section of chromosome 16 from S. cerevisiae
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Higher eukaryotes tend to have very spacious
genomes.
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What is a good definition of a genome?

• A haploid organism has one set of chromosome(s).
• Example?
• A diploid organism has two sets of chromosomes.
• Example?
• A polyploid organism has several sets of
  chromosomes.
• Example?

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What is a good definition of a genome?

• String all the chromosomes from a representative
  set together, end to end, and read the sequence
  of the DNA.
• The genome is the information content represented
  by a single set of chromosomes.
• The human genome has 46 pairs of chromosomes.
• Humans are diploid, so the genome is split over
  23 pairs of chromosomes.
• About 3 billion base pairs of DNA.

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What does the human genome look like?
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4 deoxy and 1 dideoxy NTP
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4 deoxy and 1 dideoxy NTP
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4 deoxy and 1 dideoxy NTP
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The human genome project was a collaborative
effort
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..then it was a race
NOT a code that was cracked in the 1960s
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that everyone won (sort of).
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Sequenced Genomes
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Sequenced Genomes
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Eukaryotic genome sequence complexity

• Eukaryotes have single copy, middle repetitive
  and highly repetitive DNA
• Single copy includes DNA encoding genes (5 of
  the human genome)
• Middle repetitive sequence includes some coding
  parasitic sequences (e.g., transposable elements
  50 of the human genome)
• Highly repetitive sequence are low complexity,
  include satellite sequences

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Satellite sequences?

• Nothing to do with outer space.
• Satellite sequences are so called because they
  tend to be AT rich and thus have a lower density
  than most other sequences.
• So where would you expect to see these sequences
  on a density gradient?
• Hint what happens to satellites in space?

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Satellite sequences?

• Nothing to do with outer space.
• Satellite sequences are so called because they
  tend to be AT rich and thus have a lower density
  than most other sequences.
• So where would you expect to see these sequences
  on a density gradient?
• Hint what happens to satellites in space?

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Eukaryotic genome sequence complexity
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What is sequence complexity?DNA re-association
kinetics
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What is sequence complexity?DNA re-association
kinetics
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What proportion of the genome is single copy (sc)?
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C-value paradox

• The amount of DNA in the haploid cell of an
  organism is not related to its evolutionary
  complexity or number of genes.

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C-value paradox
From Biol. Rev. (2001) 7665-101
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How to resolve the C-value paradox?

• Genome size does not reflect organismal
  complexity.
• Genome size does not reflect the number of genes.
• Sometimes, even closely related organisms have
  highly divergent genome sizes!
• Obviously, a genome does not serve a purely
  genetic function.
• So, what is the function of all that non-coding
  DNA?
• Genome size correlates positively with
  cell/nuclear size.
• Genome size correlates negatively with cell
  division rate.

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Eukaryotes have a BIG packaging problem

• How do you fit approximately 2 meters (human
  diploid nucleus) into a space that averages maybe
  5 millionths of a meter wide?
• How do you replicate, repair and transcribe
  tightly packaged DNA?