Download Lec. 26 - Genomics

Genomes & The Tree of Life
• Archaea - small circular genome
• Prokarya - small to very small (e.g., Mycobacterium)
circular genomes
• Eukarya - 3 genomes
– Mitochondrial – small to micro-sized, linear and
circular, prokaryotic origin
– Chloroplast – small, circular, prokaryotic origin
– Nucleus – large, linear chromosomes; evidence of
archaea, prokaryotic and “protoeukaryotic” origins
Chloroplast DNA in Green Plants
1.
Circular, multi-copy (20100/organelle)
2.
~160,000 bp; ~125 genes
3.
Most genes of two types:
• Photosynthesis
• Genetic functions
(mostly translation)
Tobacco
(Nicotiana
tabacum)
chloroplast
genome
From Kloppstech, Westhof et al.
Plant nuclear genome sizes are large and widely varied.
x 1000
to get
bp
Lilium
longiflorum
(Easter lily) =
90,000 Mb
Fritillaria
assyriaca
(butterfly) =
124,900 Mb
Protopterus
aethiopicus
(lungfish) =
139,000 Mb
What about genetic complexity?
How many genes do organisms
have?
Organism
Texas wild rice
Taxon
Mycoplasma
# Genes
prokaryote
517
E. coli
prokaryote
4300
Archaeoglobus
archaeon
2500
Cyanidioschyzon rhodophyte
4700
Saccharomyces
yeast
6000
Drosophila
insect
13,600
Chlamydomonas
chlorophyte
(unicell)
15,500
Arabidopsis
angiosperm,
dicot
25,000
Homo sapiens
primate
32,000
Oryza (rice)
angiosperm,
monocot
32-39,000
Mycoplasma : How many genes
essential for growth (under lab
conditions)?
• Using transposon mutagenesis, ~150 of the 517
genes could be knocked out; ~ 300 genes deemed
essential (under lab conditions), which included:
– ~100 of unknown function
– Genes for glycolysis & ATP synthesis
– ABC transporters
– Genes for DNA replication, transcription and
translation
Science 286, 2165 (1999)
Genomic and species differences
contributing to the wide range of
nuclear genome sizes
There can be great variation in the:
1. Fraction of highly repeated DNA
2. Abundance of "Selfish DNA“
(transposons, etc.)
3. Frequency and sizes of introns
– Humans have many & larger introns
4. Genetic redundancy
Genetic Redundancy
• The sizes of many gene families has
increased in some organisms more than
others
• Accounts at least partially for the relatively
high genetic complexity of plants.
Genetic Redundancy or Duplication
yeast
Drosophila Arabidopsis
No. of
genes
6200
13,600
25,000
No. of gene
families
4380
8065
11,000
1820
5535
14,000
No. of
genes from
duplication
Impact of Horizontal Transfer on
Genomes
• ~ 20% of the E. coli genome was obtained by
lateral transfer.
• Viral and bacterial pathogens can transfer
DNA from host to host.
• Some nuclear genes came from organellar
genomes (some relatively recently).
• Selfish DNAs such as mobile introns and
transposons occasionally transfer
horizontally.
What can you do with whole
genomes & sequences?
1. Predict much about the functions of a
poorly studied or difficult organism
- only ~1-5% of bacteria in the
environment are culturable
Transport
and
metabolic
pathways of
the Lyme
disease
spirochaete,
Borrelia
predicted
from the
genome
sequence.
Nature 390, 583
What can you do with whole
genomes & sequences?
1. Predict much about the functions of a
poorly studied or difficult organism.
2. Can examine genome-wide
expression patterns with microarrays
(e.g., cancer versus normal cells).
Can immobilize
1,000-5,000 DNAs
(genes) on one
microarray glass
slide.
1. Hybridize slide to
cDNAs that were obtained
by reverse transcription
from total mRNAs with a
fluorescent nucleotide.
2. Scan slide with a laser
and process fluorescent
image.
Can simultaneously compare 2
different mRNA preparations by
using different colored fluorescent
nucleotides.
Red- induced mRNA
Green- decreased mRNA
Yellow – unchanged mRNA
What can you do with whole
genome sequences?
1.
2.
3.
4.
5.
Predict much about the functions of a poorly studied or
difficult organism.
Can examine genome-wide expression patterns with
microarrays (e.g., cancer v. normal cells).
Identify new drug targets.
More rapidly identify genes linked to a trait.
Rapidly identify a gene for an identified protein by
mass spectrometry – compare mass spectrum of
the protein with the predicted patterns from all of
the genes of a sequenced genome (Proteomics).