CS273A Computational Tour of the Human Genome, Gill Bejerano, Fall 200910, Stanford

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This Friday 10am Beckman B-200 Introduction to
text processing lingos.
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Lecture 3

• Genome Content
• Repetitive Sequences
• Genes

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Our Place in the Tree of Life
? you are here
Human Molecular Genetics, 3rd Edition
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Metazoans (multi-cellular organisms)
? you are here
Human Molecular Genetics, 3rd Edition
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Vertebrates
, Stickleback
, Lizard
, Opossum
? you are here
Human Molecular Genetics, 3rd Edition
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INTERSPECIES VARIATION IN GENOME SIZE WITHIN
VARIOUS GROUPS OF ORGANISMS
Figure from Ryan Gregory (2005)
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Meet Your Genome Continues
Human Molecular Genetics, 3rd Edition
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Repeats / obile Elements ("selfish DNA")
Human Genome 3109 letters
1.5 known function
gt50 junk
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Adapted from Lunter
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TE composition and assortment vary among
eukaryotic genomes
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80
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DNA transposons
LTR Retro.
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Non-LTR Retro.
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Rice
Fugu
Mouse
Human
Mosquito
Nematode
Slime mold
Neurospora
Arabidopsis
Drosophila
Fission yeast
Budding yeast
Feschotte Pritham 2006
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Assemby Challenges
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Inferring Phylogeny Using Repeats
Nishihara et al, 2006
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Functional elements from obile Elements
Co-option event, probably due to favorable
genomic context
Yass is a small town in New South Wales,
Australia.
Bejerano et al., Nature 2006
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The amount of TE correlate positively with genome
size
Mb
Genomic DNA
3000
2500
TE DNA
2000
Protein-coding DNA
1500
1000
500
0
Rice
Maize
Mosquito
Slime mold
Brassica
Plasmodium
Sea squirt
Neurospora
Arabidopsis
Fugu
Drosophila
Nematode
Zebrafish
Mouse
Fission yeast
Budding yeast
Human
Feschotte Pritham 2006
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The proportion of protein-coding genes decreases
with genome size, while the proportion of TEs
increases with genome size
TEs
Protein-coding genes
Gregory, Nat Rev Genet 2005
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Genome Size Variability
1pg 978 Mb
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Simple Repeats

• Every possible motif of mono-, di, tri- and
  tetranucleotide repeats is vastly overrepresented
  in the human genome.
• These are called microsatellites,Longer
  repeating units are called minisatellites,The
  real long ones are called satellites.
• Highly polymorphic in the human population.
• Highly heterozygous in a single individual.
• As a result microsatellites are used in paternity
  testing, forensics, and the inference of
  demographic processes.
• There is no clear definition of how many
  repetitions make a simple repeat, nor how
  imperfect the different copies can be.
• Highly variable between genomes e.g., using the
  same search criteria the mouse rat genomes have
  2-3 times more microsatellites than the human
  genome. Theyre also longer in mouse rat.

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• Restriction enzymes recognize and make a cut
  within specific palindromic sequences, known as
  restriction sites, in the DNA. This is usually a
  4- or 6 base pair sequence.

blunt end sticky end
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DNA Fingerprint Basics

• DNA fragments of different size will be produced
  by a restriction enzyme that cuts at the points
  shown by the arrows.

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DNA fragments are then separated based on size
using gel electrophoresis.
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DNA Fingerprinting can be used in paternity
testing or murder cases.
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• From an evolutionary point of view transposons
  and simple repeats are very different.
• Different instances of the same transposon share
  common ancestry (but not necessarily a direct
  common progenitor).
• Different instances of the same simple repeat
  most often do not.

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The Gene-ome makes lt 2 of the H.G.
Human Molecular Genetics, 3rd Edition
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Gene Structure

• Signal a string of DNA recognized by the
  cellular machinery

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Gene Processing
Eukaryotic Gene Structure
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Gene Finding The Practice
Challenge The genes, the whole genes, and
nothing but the genes Problems spliced ESTs ?
legitimate gene isoform? predicting gene
isoforms tissue/condition-specific genes / gene
isoforms single exon genes pseudogenes Practice
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Evolution of Gene Finding Tools
etc
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The Human Gene Set
HGC, 2001
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Celera, 2001
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wrong!
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Signal Transduction
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Ancient Origins of Important Gene Families
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• Multigene families due to
• Single gene duplication
• Segment duplication Tandem duplication or
  duplication transposition
• a b c d e f g
• a b c d e f b c d g
• Horizontal gene transfer
• Genome-wide doubling event

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Horizontal Gene Transfer
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Horizontal Gene Transfer in the H.G.

HGC, 2001
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Or is it?
Kurland et al., 2003
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HGT between fish their parasites
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Retroposed Genes and Pseudogenes