Transcript General

The Evolution
of Genomic Diversity
Dr. Sally Otto
Department of Zoology
University of British Columbia
http://www.zoology.ubc.ca/~otto
BIODIVERSITY
GENOMIC DIVERSITY
Genome size
Genome composition
# of genes
# of chromosomes
Arrangement of genes
In this talk...
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I - Overview of genomic diversity
 Structure
 Size
II - Origins of genomic diversity
 Mutations
 Role of selection
III - Evolutionary implications
GENOMIC STRUCTURE: Number of genomes
One
HAPLOID
(e.g. bacteria, several fungi and algae, moss, our eggs and sperm)
Two
DIPLOID
(e.g. vertebrates, many plants)
More than two
POLYPLOID
(e.g. several plants, salmon, Xenopus)
GENOMIC STRUCTURE: Number of chromosomes
Mammals
100
80
www.twiga.ch/french.htm
60
40
20
Plus 51
10
20
30
40
50
Humans
Haploid chromosome number
White (1973)
GENOMIC STRUCTURE: Number of chromosomes
250
Ferns
200
150
100
Plus 216, 240, 288, 328
360, 480, 510, 630
50
25
50
75
100
125
150
175
200
Haploid chromosome number
Otto and Whitton (2000)
GENOMIC SIZE: Total content
Seed Plants
Ferns
Vertebrates
Invertebrates
Fungi
Protists
gnn.tigr.org
Bacteria
10 6
10 7
10 8
10 9
10 10
10 11
10 12
Humans
Number of basepairs in haploid genome
Cavalier-Smith (1985)
http://www.cbs.dtu.dk/services/GenomeAtlas/
GENOMIC SIZE: Number of genes
Seed Plants
Vertebrates
Invertebrates
Fungi
Bacteria
500 1000
5000 10000
50000 100000
Number of genes
http://www.ultranet.com/~jkimball/BiologyPages/G/GenomeSizes.html
Why such enormous diversity?
•
MUTATION: Genomic alterations arise frequently
• SELECTION:
Genomic alterations increase fitness
(survival or reproductive success)
MUTATION: Ploidy level
We used the ratio of even:odd chromosome numbers
to estimate the rate of polyploidization per speciation event:
• ~ 2-4% in seed plants
• ~ 7% in ferns
• Rare in animals (~180 independent cases)
Otto and Whitton (2000)
MUTATION: Chromosome number
Chromosome numbers can change by fusion and fission
as well as by polyploidization.
• e.g. Robertsonian fusions
~10-4 per gamete per generation in humans
Robertsonian
Fusion
TREE 10:397
MUTATION: Genome size
Genome size can change by:
•
•
•
polyploidization
gain or loss of chromosomes (aneuploidy)
gain or loss of DNA
e.g., replication of transposable elements
(~10-4 per TE per generation in Drosophila)
Charlesworth and Langley (1991)
Hurst and Werren (2001) NRG 2:597
MUTATION: Genome size
Relative genome size
Measurable changes in genome size are sometimes
observed over short time periods, e.g. in tetraploid yeast.
Rich media
4
4
3
3
2
2
1
1
0
500
1000
1500
Generation
2000
High salt
0
500
1000
1500
2000
Generation
Grant et al. (in prep)
Changes in genomic structure and size have been
observed in other long-term experiments:
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Duplications and deletions of regions in E. coli adapting to high
temperature (Riehle et al. 2001)

Partial chromosome loss in S. cerevisiae adapting to glucose
limitation (F. Rosenzweig pers. comm.)

Ploidy changes in S. cerevisiae adapting to glucose limitation (in
collaboration with C. Zeyl)
MUTATION: Gene duplication
Lynch and Conery (2000) scoured genome sequences
in search of very newly duplicated genes:
• 31 duplication events per genome per million years in flies
(Drosophila melanogaster)
• 52 in yeast (Saccharomyces cerevisiae)
• 383 in nematodes (Caenorabditis elegans)
Even in the absence of selection, we would expect
roughly half of genes to duplicate and fix within the
genome over a time period of 35 - 350 million years.
SELECTION: Genome or gene duplications
Flies
“It is interesting to speculate
that emergence of the complex
head structures of the
vertebrates has a basis in the
amplification of the homeobox
clusters.” – Pendleton et al. (1993)
Mammals
Hoxb-2
Hoxb-4
Can selection favor duplications to provide
greater opportunities for the evolution of novel function??
SELECTION: Genome or gene duplications
Selection cannot favor the establishment of a genomic or
gene duplication on the basis of novel beneficial functions
that might appear millions of years in the future.
Evolution is myopic.
What are the immediate effects of the duplication?
SELECTION: Gene duplication
New gene duplications, if they have any effect on fitness,
are typically deleterious:
• Incomplete or inaccurate copying
• Abnormal levels or timing of gene expression
• Disruption of other genes or regulatory regions by insertion
• Promotion of deleterious chromosomal rearrangements
Very deleterious duplicates are unlikely to persist, however!
The fate of a duplicate depends on selection...
N
12
D
B
10
D
B
8
6
4
2
-0.03
-0.02
-0.01
0.0
0.01
0.02
Density among fixed duplicates
Density among new duplicates
N
0.03
Effect on fitness
(D = Deleterious, N = Neutral, B = Beneficial)
New gene duplicates rarely increase fitness, but those
that do are much more likely to persist.
Otto and Yong (2002)
Examples of immediately beneficial gene duplications:
Selection for more gene product:
• Glutathione S-transferase genes in houseflies subjected to insecticides
(Wang et al., 1991)
•
Esterase genes in mosquitoes subjected to insecticides
•
Metallothionein genes in Drosophila subjected to high metal concentrations
(Mouchès et al., 1986; Guillemaud et al., 1999)
(Maroni et al. 1987)
Selection to fix two alleles (variants) of a gene:
•
Opsin genes in primates
Allele L allows red color vision; allele M allows green color vision (Jacobs et al., 1996; Tan and Li, 1999)
L
L
M
M
L
M
www.inf or am p.net/~ornstn/ m a da ga sc ar .htm l
ra che l974.tripod.c om/af ric aphotos/ id2.htm l
•
Acetylcholinesterase in mosquitoes subjected to insecticides
Allele R is resistant but less effective than allele S (Lenormand et al., 1998)
Once established, what are the long-term effects
of gene or genome duplications???
•
ADAPTATION: Ability of a population to track a
changing environment.
• SPECIATION:
Tendency for populations to diverge
and become reproductively isolated.
POLYPLOIDY
ADAPTATION
“…the large amount of gene duplication
dilutes the effects of new mutations and
gene combinations to such an extent
that polyploids have great difficulty
evolving truly new adaptive gene complexes.”
- G. L. Stebbins (1971)
The rate of increase in fitness due to the fixation of
new beneficial mutations (a) is:
Fixation probability
Fitness effect
Rate of appearance
Haploids
W1n = (N ) (2 s) s
Diploids
W2n = (2N ) (2 h s) s
Tetraploids: W4n = (4N ) (2 h1 s) s
N = Population size 
= Beneficial mutation rate
1+s = fitness of a haploid s
1+hs = fitness of Aa dip loids
1+h1s = fitness of AAAa tetraploids
The ploidy level with the highest rate of adaptation:
1.0
0.8
Tetraploidy
0.6
0.4
0.2
Haploidy
0.2
Diploidy
0.4
0.6
0.8
1
Dominance level in diploids (h)
= additive case
When beneficial mutations are highly expressed (dominant),
polyploids adapt fastest.
When beneficial mutations are masked (recessive),
haploids adapt fastest.
The blanket statement that
polyploids should
adapt more slowly is false.
Otto and Whitton (2000)
Dicots
www.apsnet.org
Average species richness
SPECIES RICHNESS
175
95% CI
150
125
100
75
50
25
0-25%
25-50%
50-75%
75-100%
Degree of polyploidy in dicot genera
Significant positive linear regression based on ranks (p = 0.017)
Otto and Whitton (2000)
A similar positive relationship between polyploidy and species
richness was reported for the angiosperm flora of the
Pyrenees (Petit & Thompson 1999)
Several possible explanations:
1. Polyploidization can act as a speciation mechanism,
causing immediate reproductive isolation between
individuals with different chromosome numbers.
2. Older genera are more likely to exhibit a greater mixture of
ploidy levels and be speciose.
3. Polyploids may adapt faster to local conditions and thereby
promote divergence and speciation.
Polyploidization may increase speciation rates and promote
the evolution of biodiversity,
but whether and why this occurs needs further study.
CONCLUSIONS
Genomic size, structure, and content are tremendously
diverse.
This diversity largely reflects a high rate of mutation,
leading to polyploidization, gain or loss of
chromosomes, and gain or loss of DNA.
While genomic structure can affect both the ability of a
population to adapt and to speciate, the role that
genomic structure has played in the major evolutionary
transitions of life remains enigmatic.
Acknowledgments
Collaboration and assistance:
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Maren Friesen
Alex Grant
Jordana Tzenova
Kim Ryall
Jeannette Whitton
Paul Yong
Discussions:
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UBC evolutionary group
Funding:
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NSERC (Canada)
CNRS (France)