Download Genome duplication associated with diversification of the angiosperms

Significance of
variation
McDonald and Kreitman 1991
Mutations are the raw material of evolution
• Source of new alleles
• Source of new genes
• Produce heritable variation that is transmitted across
generations
1. Small-scale mutations
2. Macromutations
• Polyploidy
• Doubling of whole genomic DNA
Genome and gene duplications create
evolutionary novelty
Secretory calcium binding
phosphoprotein (SCPP)
gene family
Tunicate
Ray-finned fish
In mammals,
formation of
tooth, bone and
milk depends
upon SCPP
Lobe-finned fish
• Vertebrate evolution
punctuated by three
widespread gene or
genome duplications
• Associated with:
• Increases in
morphological
complexity
• Adaptive
radiations in body
design
• Is genome duplication
the explanation?
Sanetra et al.Frontiers in Zoology 2005 2:15
Genome duplications = evolutionary novelty
• If this is true, what pattern would you expect to see
on a phylogenetic tree after genome duplication
event in terms of species diversity? Number of
• Burst of diversification
families per
clade
• Not supported
Clades
Extant lineages
Extinct lineages
Evolution of jawed fish
Donoghue and Purnell 2005
Genome duplications = evolutionary novelty
• If this is true, what pattern would you expect to see
on a phylogenetic tree after genome duplication
event?
• Burst of diversification
• Not supported
Fossil
evidence
Extant lineages
Extinct lineages
Evolution of ray-finned fishes
Donoghue and Purnell 2005
Genome duplications
provide robustness
• Focus on the high rate
of extinction before
duplication
• Provides robustness
against extinction
Extant lineages
Extinct lineages
Crow and Wagner 2005. Mol. Bio. Evol. 23:887-892
Genome duplication associated with
diversification of the angiosperms
De Bodt et al. 2005
• Appear suddenly in
the fossil record
Darwin referred to the rapid rise and
early diversification of the angiosperms
as an “abominable mystery”
• Tried to identify a single
causal factor
• Described his efforts
“wretchedly poor”
Letter to J.D. Hooker dated July 22 1897
Genome duplication associated with
diversification of the angiosperms
De Bodt et al. 2005
• Appear suddenly in
the fossil record
• Polyploidy created
developmental and
regulatory gene
families found in
angiosperms
Are genome-wide and single-gene
duplications equally valuable from an
evolutionary perspective?
• Genes involved in signal transduction
transcriptional regulation and are
preferentially retained following polyploidy
Maere et al. 2005. PNAS.102,
5454–5459
Blanc & Wolfe. 2004.Plant Cell
16, 1679–1691
Seoighe & Gehring. 2004.
Trends Genet. 20, 461–464
Are genome-wide and single-gene
duplications equally valuable from an
evolutionary perspective?
• Genes involved in signal transduction
transcriptional regulation and are
preferentially retained following polyploidy
• Developmental genes also retained at
higher frequency
• Fewer of these genes survive single gene
duplications
• Transcription factors and genes involved in
signal transduction show high dosage
effects
• Protein components must be present in
stoichiometric qualities
Polyploidy in plants is an ancient and
ongoing process
Diploid
Meiotic
Nonreduction
X
Fertilization
Tetraploid
• 70-80% of plants have
polyploidy origins
• Speciation via
polyploidy has been
observed in modern
times
Many species posses a
ploidy series
2x
4x
6x
8x
10x
Chrysanthemum
Do higher ploidy levels
possess greater potential
for evolutionary change?
More gene
products
Greater genetic
diversity
Opportunity for
duplicated genes to
diverge in function
More gene
interactions
2x
4x
6x
8x
10x
Do higher ploidy levels possess greater
Will
polyploids
evolve
faster?
potential for evolutionary change?
Figure 1. Countable chromosome images from the
ploidy levels included in this artificial selection
experiment
Diploid
Figure 1. Countable chromosome images from the
ploidy levels included in this artificial selection
experiment
Chromosome count = 18
Diploid
Tetraploid
G0
Chromosome count = 18
Chromosome count = 36
Tetraploid
G1
Chromosome count = 36
G2
G3
G4
control
Days to flower
control
Days to flower
Artificial
selection on
timing of
flowering
% of Selection lines that are
signficantly different than the controls
Chromosome count = 18
Figure 1. Countable chromosome images from the
ploidy levels included in this artificial selection
experiment
Tetraploid
Diploid
Chromosome count = 36
Chromosome count = 18
100
Tetraploid
Chi-square = 9.9; P = 0.002
80
Chromosome count = 36
60
40
20
0
Tetraploid
Diploid
Do ploidy levels differ in their geographic
distributions?
Solidago altissima
Late goldenrod
2x
4x
>4x
Genome size (pg DNA)
6.5
6.0
F3,768 = 2591
P < 0.0001
5.5
5.0
4.5
4.0
3.5
3.0
Diploid Triploid Tetraploid Higher
Cytotypes
Do alleles differ in their geographic
distribution?
Futuyma 1998
• Cline in alcohol
dehydrogenase locus
of Drosophila
melanogaster
• Repeated on three
continents
Are different alleles being favored
over time?
Anderson et al. 2005. The latitudinal cline in the In(3R)Payne inversion
polymorphism has shifted in the last 20 years in Australian Drosophila
melanogaster populations. Molecular Ecology 14: 851–858
Selectionist mission
Link biochemical differences to fitness in nature
Few well-known examples where natural selection is
clearly involved in the maintenance of enzyme
polymorphism
http://anthro.palomar.edu/synthetic/images/map_of_sickle_cell_frequencies.gif
Significance of variation
• Chimps and humans differ in
1% of our genes
• ~3,400,000 nucleotides
• ~60,000 amino acid differences
• What proportion of these
differences have been fixed
because they were beneficial
and allowed us to adapt to our
environments?
• How many of these differences
were simply fixed by random
genetic drift?
To what extent does natural selection
operate at the molecular level?
Some history…
Significance of variation
• Study of variation at the molecular level began with
proteins (allozymes).
Hubby and Lewontin. 1966. A molecular approach to the study of genic heterozygosity in
natural populations. The number of alleles at differ loci in Drosophila pseudoobscura.
Genetis 54:577-94.
Harris 1966. Enzyme polymorphism in man. Proc. Roy. Soc. B. 164:298-310.
• Discovered astonishing level of polymorphism
• Challenged our fundamental understanding of how
adaptive evolution occurs
• Most variation must be neutral – Kimura’s neutral theory
of evolution (1970)
“The maintenance of abundant polymorphism
and heterozygosity in populations demands,
however, an explanation… The easiest way to
cut the Gordian knot is, of course, to assume
that a great majority of the polymorphisms
observed involve gene variants that are
selectively neutral, that is, have no appreciable
effects on the fitness of their carriers”
Dobzhansky 1970
The beginning of neutralistselectionist debate
The central tenants of the neutral theory
• Kimura (1968)
• Most mutations are deleterious and are rapidly
eliminated
• A very small number of mutations are favorable and
are rapidly fixed
• Most of the variation that we observe within species
is selectively neutral and is governed by the
interplay of mutation and drift
• Most differences between species are simply due to
the random fixation of mutations
Neutral theory seemed to work!
• Estimates of overall heterozygosity
Nei 1983. Genetic polymorphism and role of mutation in evolution. In The evolution of genes and
proteins p. 165-190
• Distribution of single locus heterozygosity
Nei et al. 1976 Testing the neutral mutation hypothesis by distribution of single locus heterozygosity.
Nature 262:491-493
• Variance in heterozygosity
Gojobori 1982 Means and variances of heterozygosity and protein function. In Molecular Evoluton,
Protein Polymorphism and the Neutral Theory pp 137-150
• Number of alleles per locus
Chakaraborty et al. 1980. Statistical studies on protein polymorphism in natural populations. III.
Distribution of allele frequencies and the number of alleles per locus. Genetics 94:1039-1063
• The correlation of single-locus heterozygosity between
related species
Braverman et al. 1995. The hitchhiking effect on the site frequency spectrum of DNA polymorphism
Genetics 140:783-795
A few clear cases showed accelerated
protein evolution
Duplicate genes
• Faster rates of nonsynonymous replacement than of
synonymous replacement
• High selective value of protein divergence
• Hemoglobins
• Visual pigments
• Adrenergic receptors in humans
• Antigen recognition sites in humans and mouse
• Immunoglobulins
• Growth hormone genes in humans and bovines
A few clear cases showed accelerated
protein evolution
Can you make this
Duplicate genes
into a general
test?
• Faster rates of nonsynonymous replacement than of
synonymous replacement
• High selective value of protein divergence
• Hemoglobins
• Visual pigments
• Adrenergic receptors in humans
• Antigen recognition sites in humans and mouse
• Immunoglobulins
• Growth hormone genes in humans and bovines
What can we learn by comparing the rate
of synonymous and nonsynonymous
replacements?
• New light recently shed on debate because of:
• Increase in DNA sequence data
• New methods of analysis
Does selection act at the molecular level?
• McDonald-Kreitman test (MK)
• Neutral theory predicts the amount of
variation there should be within and
If neutral - expect more syn or nonsyn?
between species
• We can use sequence data to
calculate the amount of variation
Divergence
within a species (polymorphism) to
Ds and Dn
the amount of variation between
species (divergence):
1. Synonymous (no change in
amino acid sequence or
regulatory sequences)
2. Nonsynonymous (change in
amino acid sequence or
Polymorphism
Ps and Pn
regulatory sequence)
If neutral - expect more syn or nonsyn?
The verbal argument…
• McDonald-Kreitman test (MK)
• Nonsynonymous mutations that are
adaptive () contribute to
divergence (Dn) but not so much to
polymorphism (Pn)
• Rapidly fixed by selection so they
are not segregating within species
• Synonymous mutations will
accumulate at the neutral rate (Ds
and Ps)
• If most molecular evolution is
neutral then:
• If under selection?
Dn Pn
>
=
Ds Ps
Polymorphism
Ps and Pn
Divergence
Ds and Dn
The mathmatical argument…
Time it takes a new mutation to become fixed if that is
its destiny from Kimura’s equations
Ps = 4NeLsk
Pn = 4NeLnfk
Ds = 2Lst
Dn = 2Lntf
1-
Dn–=DP
= 1
nn
sP
Ds DP
ss
nP
Ne = effective population size
 = nucleotide mutation rate
Ls = number of synonymous sites
k = constant
number sequences sampled
sampling strategy
demography
Ln = number of nonsynonymous
sites
f = proportion of amino acid
mutations that are neutral
t = time since divergence of two
species
 = proportion of nonsynonymous
mutations that are adaptive
MK test for adaptive evolution
115 genes in two species of Drosophila
Divergence
Non-synonymous
Synonymous
= 1 – DsPn
D nP s
Polymorphism
3648
7365
0.49
Dn = Pn
Ds Ps
439
1741

0.25
= 1 – (7365)(439)
(3648)(1741)
= 0.49
Inferring the strength of adaptive evolution
• From this and other studies, adaptive value evolution in
Drosophila protein-coding sequences converging at
~50%
• Can extrapolate to the whole genome
• If  = 0.45, then Drosophila would have one substitution
every 45 years or 450 generations
• 22,000 substitutions per million years
Survey of rate of adaptive evolution at
molecular level
Eyre-Walker 2006
Is the pattern uniform across species?
• No.
• The proportion of nonsynonymous mutations that are
adaptive is particularly low in comparisons of humans
and other organisms
• Ranges 0-35%
• Bias in 35% estimate of Fay et. al 2001
• Used genes associated disease and other critical
function
• Also little evidence of adaptive evolution in Arabidopsis.
• High levels of adaptive evolution in viruses and bacteria
What do all these substitutions do?
• D. melanogaster and D. simulans differ by 110,000
adaptive amino acid differences
• Species are almost identical morphologically
• Physiology
• Ecology
• Arms race between hosts and parasites
• “It might be that we just have no idea how complex the
environment really is and how it is constantly changing
in ways that challenge organisms to adapt.” (EyreWalker 2006)
Evolution is the interplay between two
tangled banks
Natural turbulence
Genetic turbulence