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Transcript
The Graph of Life
Dennis Shasha
Joint work with
Kenneth Birnbaum
Treester system by: Matt Olim
Phylogenetic Reconstruction
(careful: root is bottom-most)
Strictly non cyclic
•maximum parsimony
•maximum likelihood
Character Conflict
(one feature/two places)
Why Conflict?
Helianthus petiolaris
Helianthus annuus
X
sunflowers
ancient hybridization
event ~100,000 years
ago
Helianthus paradoxus
Phylogenetic … Trees?
H. paradoxus
Adapted from
Rieseberg et al.
1991
Phylogenomics
•takes many individual gene trees (technically,
orthologs)
•combines data -- e.g., sequence concatenation
•obtains a single tree from combined data -hopefully with high confidence!
• Rokas et al. (Nature 2003): 20 trees is enough
(based on 8 yeast species).
Observation: Individual Trees Vary
Example: multiple gene trees of eight sequenced yeast species
From Rokas et al. 2003
For this data set
Conflict Smoothed by Combining Data
100%
Most
parsimonious
tree from 106
individual trees
concatenated
100%
100%
100%
100%
S. cerevisiae
S. paradoxus
S. mikatae
S. kudriavzevii
S. bayanus
S. castellii
S. kluyveri
C. albicans
But then why do the trees vary?
•Noise
(maybe trees for a given gene aren’t right)
•Hybridization
(different species have viable offspring)
•Horizontal gene transfer, e.g. bacterial orgy
•Convergent evolution
(think cactus, only at genomic level)
Whatever reason: settling on a consensus tree may throw
away much information.
Finding Hidden Signals
•Begin with several trees for each orthologous gene.
•Not only the most parsimonious ones but the top
few.
•1. Find trees in descending order of popularity and
see whether genes have interesting commonalities.
•2. Generate a network from popular trees.
Data SetUp
•Using PAUP, generated top 10 most parsimonius
trees for each orthologous gene that was present in
all eight species.
• Popularity contest:
loop
find most popular tree
spit out tree and associated genes
remove genes having that tree
end loop
• Unused Popularity contest: same but don’t
remove.
Findings
•Genes following the Rokas consensus tree are
normal in every way. 378 of those. (We expanded
analysis)
(((((((Scer,Spar),Smik),Skud),Sbay),Scas),Sklu),Calb) [count378]
• 46 genes associated with next tree somewhat
closer to one another than expected, but not quite
at the 5% threshold.
(((((((Scer,Spar),Smik),Skud),Sbay),Sklu),Scas),Calb) [count46]
•13 genes associated with next tree are well within
the 5% threshold of being close to one another and
on only 5 of 17 chromosomes.
(((((Skud,Sbay),((Scer,Spar),Smik)),Scas),Sklu),Calb) [count13]
Other Odd Properties of
the 13
• 4 of the 13 genes are annotated as having ATPase
or ATP synthase (only 92 out 6,000 genes have
similar annotations).
• Consensus tree is quite different from 13 gene
tree.
(((((((Scer,Spar),Smik),Skud),Sbay),Scas),Sklu),Calb)
(((((Skud,Sbay),((Scer,Spar),Smik)),Scas),Sklu),Calb)
The odd 13
S. cerevisiae
S. paradoxus
S. mikatae
S. kudriavzevii
S. bayanus
consensus tree
S. castellii
S. kluyveri
C. albicans
S. cerevisiae
S. paradoxus
S. mikatae
Remnants of an ancient
hybridization event?
S. kudriavzevii
S. bayanus
Parallel gene evolution
among ATP-related
genes and others ?
S. castellii
S. kluyveri
C. albicans
The Graph
0.3
0.7
Network Building
•LatTrans: Addario-Berry. Models lateral transfer of
genetic information. Makes some assumptions
about mutation rates. Always between siblings.
•Model horizontal gene transfer: Lake and Rivera.
Procaryotic model that tries to distill fundamental
tree of life assuming Markov model. Vs. Doolittle
Network Building 2
•Moret, Nakleh et al propose "galled networks"
which are networks where hybridizations don't
intersect. They argue that this limitation makes
sense, because there are modest levels of
recombination.
•Our approach: start with reliable gene trees and
build a “conservative” species graph. No statistical
assumptions except quality of tree branching.
Nomenclature
Gene Tree A (gene A and orthologs)
A11
A122
A121
A2
extant gene
variants
A12
missing ancestral
gene variants
A1
A1 is parent of A12
A
Assumptions
variant = one of the orthologs of a gene
1. A variant is likely to arise only once in the tree or
network (convergent phenotype yes; but not same
sequence).
2. If species X has one parent P, then for each gene
A, the variant of A in X must be the direct
descendent of the variant in P or equal to that
variant (e.g., A12-->A121)
3. If species X has more than one parent, then for
each gene A, the variant of A must descend/be
equal to the variant in exactly one parent.
First: characterize species by tree position
sp1 sp2
sp1: A1
sp2: A21
sp3: A22
sp1:B22
sp2:B21
sp3:B11
sp3
sp1(A1 B22)
sp2(A21 B21)
sp3(A22 B11)
sp1 In a tree for sp1 and sp2,
those species must both be
descendants of node N
B2
where B2 arises. Further, the
split between A1 and A2 must
B
descend from N.
sp3 sp2
Let’s Illustrate Dependencies
Species:
sp1(A1 B22), sp2(A21 B21), sp3(A22 B11)
From sp1 and sp2, B2 arises before A1 splits from
A2. Birth(B2) before birth(A2)
From sp2 and sp3, A2 arises before B1 splits from
B2. Birth(A2) before birth(B2).
Shows that tree is not possible. We choose a tree
that is consistent with as many species as possible
and then add the remaining species using as few
edges as possible. Weights indicate number of
species.
One possible graph
sp1 sp2
sp3
sp1: A1
sp2: A21
sp3: A22
sp1:B22
sp2:B21
sp3:B11
m1 (A B)
m2 (A B1)
sp1(A1 B22)
m3 (A2 B2)
sp2(A21 B21)
sp3 sp2
sp1
m2
stranded taxa
sp3(A22 B11)
sp3
sp2
sp1
m3
B2
B
“base tree”
m1
Does it make sense?
•The three trees seem quite different:
(((((((Scer,Spar),Smik),Skud),Sbay),Scas),Sklu),Calb)
(((((((Scer,Spar),Smik),Skud),Sbay),Sklu),Scas),Calb)
(((((Skud,Sbay),((Scer,Spar),Smik)),Scas),Sklu),Calb)
In particular, Skud seems to move a lot. But our graph showed
multiple ancestry for Scas only.
Well, maybe
•Observe that Scer, Spar, Smik always form same
subtree, so let’s replace by a single node xxx. Then
remove Scas because we are interested only in
whether what remains forms a tree. Here is what we
get:
((((((xxx),Skud),Sbay)),Sklu),Calb)
((((((xxx),Skud),Sbay),Sklu)),Calb)
(((((Skud,Sbay),(xxx))),Sklu),Calb)
Graphing Phylogenies
•infer ancestral states for each gene tree
•find tree that includes a maximal set of species
(“conservative” base tree)
•infer parents of remaining species from ancestors
(graph)
Summary
Phylogenomics generates large datasets to overcome
conflicting signals in phylogenetic trees, but may cause us
to ignore biological signals.
•Phylogenetic Networks -- A Graph of Life -- can suggest
gene transfers through hybridization or some other reason.
• Basic method: start with gene trees, take reliable
bifurcations (over 60%) and combine them into a
consensus directed graph that suggests possible paths of
gene transfer.
•Software is general purpose and available.
Cause of Conflict?
Examined 3 best supported network edges
(most gene tree support)
Traces of an anicent hybridization
•Possible expectation: blocks of genes with common ancestry
•none of the genes contributing to network edge are clustered
on the chromosome IN C. cerevisiae but 13 oddballs are
something of an exception
•…total number of genes is 108, so synteny impossible. Will
extend this in future.
Convergent Evolution
•Do genes comprising network edges have a common
function? No but still looking.
Major Cyclic Edges
12 gene trees
S. cerevisiae
S. paradoxus
S. mikatae
S. kudriavzevii
15 gene trees
24 gene trees
S. bayanus
S. castellii
S. kluyveri
C. albicans
Revised from Rokas
et al. 2003