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Phylogenetics 2:

Phylogenetic and genealogical homology

Phylogenies distinguish homology from similarity

•  Analogy •  Homology

•  Polarity •  Ancestral character •  Derived character

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human cow rabbit rat opossum GTG CTG TCT CCT GCC GAC AAG ACC AAC GTC AAG GCC GCC TGG GGC AAG GTT GGC GCG CAC ... ... ... G.C ... ... ... T.. ..T ... ... ... ... ... ... ... ... ... .GC A.. ... ... ... ..C ..T ... ... ... ... A.. ... A.T ... ... .AA ... A.C ... AGC ... ... ..C ... G.A .AT ... ..A ... ... A.. ... AA. TG. ... ..G ... A.. ..T .GC ..T ... ..C ..G GA. ..T ... ... ..T C.. ..G ..A ... AT. ... ..T ... ..G ..A .GC ... GCT GGC GAG TAT GGT GCG GAG GCC CTG GAG AGG ATG TTC CTG TCC TTC CCC ACC ACC AAG ... ..A .CT ... ..C ..A ... ..T ... ... ... ... ... ... AG. ... ... ... ... ... .G. ... ... ... ..C ..C ... ... G.. ... ... ... ... T.. GG. ... ... ... ... ... .G. ..T ..A ... ..C .A. ... ... ..A C.. ... ... ... GCT G.. ... ... ... ... ... ..C ..T .CC ..C .CA ..T ..A ..T ..T .CC ..A .CC ... ..C ... ... ... ..T ... ..A ACC TAC TTC CCG CAC TTC GAC CTG AGC CAC GGC TCT GCC CAG GTT AAG GGC CAC GGC AAG ... ... ... ..C ... ... ... ... ... ... ... ..G ... ... ..C ... ... ... ... G.. ... ... ... ..C ... ... ... T.C .C. ... ... ... .AG ... A.C ..A .C. ... ... ... ... ... ... T.T ... A.T ..T G.A ... .C. ... ... ... ... ..C ... .CT ... ... ... ..T ... ... ..C ... ... ... ... TC. .C. ... ..C ... ... A.C C.. ..T ..T ..T ...

Alignment of mammalian beta-globin gene sequences

Homology: similarity among two or more individuals or lineages in a feature/character, or character-state, that is the result of inheritance from a common ancestor

Homologous character verses Homologous character state

ACG TAC TAA

ACG TAT TAA

ACG TAT TAA

C

T

ACG TAC TAA

ACG TAT TAA

ACG TAT TAA

C

T

Molecular evolution: positional homology

DNA alignment

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Phylogenies distinguish homology from similarity

ACG TAC TAA

ACG TAT TAA

ACG TAT TAA

C

T

Phylogenetic perspective on homologous characters and homologous character states

Ancestral character states

ACG TAT TAA

ACG TAC TAA

ACG TAC TAA

C

C

Ancestral character states

C ⇒ T

SYNAPOMORPHY: a shared derived character state in two or more lineages. These must be homologous in state. This represents a true phylogenetic similarity

APOMORPHY: a derived character state unique to a single lineages

Implicit in the above alignment is the assumption of positional homology for the “red” position above. At this position C and T are non-homologous character states. Note that the pair of T’s in the first example, and the pair of C’s in the second example represent homologous character states.

Phylogenies distinguish homology from similarity

It is possible for character-states to be identical but non-homologous (Homoplasy)

1.  Convergence

2.  Reversal

3.  Parallelism

Homoplsy arises in molecular datasets when multiple substitutions occur at a single site.

- “multiple substitutions”

- “multiple hits”

- “superimposed substitutions”

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Phylogenies distinguish homology from similarity: convergence

ACG GAT TAA

ACG GAG TAA

ACG GAA TAA

T

G G ⇒ A

T

ACG GAA TAA T ⇒ C ⇒ A

Convergent (non-phylogenetic) similarity of nucleotide character states; i.e., homoplasy

Phylogenies distinguish homology from similarity: reversal

ACG GAA TAA

ACG GAT TAA

ACG GAT TAA

A

T

A

ACG GAA TAA A ⇒ C ⇒ A

Reversal leads to non-homologous similarities in character state.

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Phylogenies distinguish homology from similarity: parallelism

ACG GAA TAA

ACG GAT TAA

ACG GAA TAA

A

A

A

ACG GAT TAA A ⇒ T

Parallel evolution leads to non-homologous similarities in character states.

A ⇒ T

Evolutionary dissociation

“A change in linkage or effects that particular traits from different levels of biological organization have on each other over evolutionary time”

⎯ Meyer and Mindell (2001)

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Evolutionary dissociation

Adapted from: Mindell and Meyer (2001) Trends Ecol Evol. (16) 434-440.

Dissociation events

GENE A is homologous as a molecular character in all five lineages GENE A’s functional role in development also is homologous in all five lineages The “character state” of GENE A is NOT homologous in lineage 5 as compared with lineages 1 and 2 even though they have the same role! This is another example of homologous characters with non-homologous character states.

The phylogenetic concept of homology allows distinction between homologous characters and non-homologous characters states in the case of evolutionary dissociation.

Role 2: morphologically similar structures with different molecular evolutionary basis

Evolutionary dissociation

Homologous genes control the basis for non-homologous structures. Apparently, Genetic co-option has occurred. Gene duplication provides one mechanism; non-homologous character states within homologous positions of a gene provides another.

Butterfly embryo Sea urchin larva

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Alternatives to phylogenetic concept of homology

Serial Homology refers to repeated structural units of morphology of an organism.

•  It seems reasonable that such units are derived from homologous genes or developmental processes; whether this assumption turns out to be generally applicable to morphological features exhibiting serial homology has not yet been demonstrated.

Functional homology is generally used when the functional attributes of organisms are similar due to shared ancestry.

•  However, due to a long history of using this term to denote simple similarity, one should not assume this usage unless unequivocally stated.

Biological homology is defined by Wagner (1989) as morphological structures that share “developmental constraints, caused by locally acting self-regulating mechanisms or organ differentiation”.

•  Although phylogeny can be used to help diagnose such homology, the definition does not explicitly include the condition of shared ancestry.

Alternatives to phylogenetic concept of homology

percent homology

For DNA (or amino acid) sequences use percent similarity

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Trees within trees

A B

C D

E F

I

Conventional representation

A BB

C D

E F

I

Conventional representation

A

C D

E F

I

C D

E F

I

B

Path 1 Path 2

A

C D

E F

I

AA

CC DD

EE FF

II

C D

E F

I

B

C D

E F

I

BB

Path 1 Path 2

Trees within trees: reticulation

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Trees within trees

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Trees within trees

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Trees within trees

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Trees within trees

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Trees within trees

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Population genetics: coalescent theory to study populations

Trees within trees

time

Drift

Selection

Population history

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Trees within trees

Polymorphism and substitution (highly simplified) along a branch of a phylogeny

Time

Residence time: the time that a particular neutral polymorphism is present in a population.

Mean residence time is determined by effective population size (Ne)

Population substitution 1 Population substitution 2 Population substitution 3

Coalescent

GAC

GAT

GAT

A

T

A

GAG A ⇒ C ⇒ A ⇒ G

A ⇒ C C ⇒ A A ⇒ G

Forms of homology (for genes)

1. ORTHOLOGY. Orthologous genes are derived from the divergence of an organismal lineage; i.e., a speciation event. Thus if we look at orthologs on a phylogeny we see that their most recent common ancestor represents the coalescence of two organismal lineages.

2. PARALOGY. Paralogous genes are derived from the divergence event within a genomes; i.e., a gene

duplication event. In this case if we look at paralogs on a phylogeny we see that they coalesce at a gene duplication event.

3. PRO-ORTHOLOGY. A gene is pro-orthologous to another gene if they coalesce at a speciation event that

predates a gene duplication event. Thus a single-copy gene in organism A is pro-orthologous to a gene that is present in multiple copies in organism B due to gene duplication events that followed the divergence of organisms A and B.

4. SEMI-ORTHOLGY. This is a term that simply takes the reverse perspective of pro-orthology. Any one of the

multi-copy genes in the genome of organism B is said to be semi-orthologous to a single copy gene in the genome of organism A, if the most recent common ancestors of those genes coalesce at a point in time that predates the gene duplication event.

5. PARTIAL HOMOLOGY. This refers to the situation that arises when the evolutionary histories of different

segments within the same gene coalesce at different ancestors. This can arise from evolutionary processes such as homologous recombination or exon shuffling.

6. GAMETOLOGY. Gametologs coalesce at an event that isolated those genes on opposite sex

chromosomes; i.e., they coalesce at the point when they became isolated from the process of recombination.

7. XENOLOGY Genes that coalesce at either a speciation or duplication event, but whose evolutionary

histories do not fit with that of the organismal lineages which carry such genes due to one or more lateral gene transfer events.

8. SINOLOGY. Homologous genes found within the same organism’s genome have different

evolutionary histories due to the fusion of formerly evolutionarily independent genomes, such as in endosymbiosis.

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The mammalian Ldh-A and Ldh-C gene family is used as an example to illustrate the various forms of homology (ORTHOLOGY, PAROLOGY, PRO-ORTHOLOGY, and SEMI-ORTHOLOGY) that are important when dealing with gene families.

Pro-orthologs pre-date the involved duplication event

Examples of different types of homology in gene families: Homo and Rattus (rat) Ldh-C are orthologous. Homo Ldh-C and Homo Ldh-A are paralogous. Homo Ldh-C and Rattus Ldh-A also are paralogous. Gallus (chicken) Ldh-A is pro-orthologous to both Homo Ldh-C and Homo Ldh-A. Homo Ldh-C is semi-orthologous to the Gallus Ldh-A. All mammalian Ldh-A genes are semi-orthologous to the non-mammalian Ldh-A. Note that the gene duplication that gave rise to the Ldh-C gene is specific to an ancestor of all present-day mammals. Mammalian Ldh-C and Ldh-A genes are paralogous. All Ldh-C and Ldh-A are homologous.

Mus

Cricetinae

Homo

Gallus

Sceloporus

Rattus

Sus

Homo

Sus

Rabbit

Mus

Rattus

Ldh-A

Ldh-C

Gene duplication event

Organism history can different from gene history

Selected examples (in notes):

•  Birth-death evolution in gene families

•  Trans-species evolution •  Recombination

•  Lateral gene transfer (LGT)

Other sources:

•  Statistical error

•  Human error

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1. Ancestral polymorphism

1. Ancestral polymorphism: residence times

•  rate to fixation [under drift] slows with increasing in Ne •  ultimate fate is fixation or loss

•  Larger Ne yield larger residence time of a polymorphism in a population

If we run this simulation long enough it will go to fixation or loss; it just takes much longer

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1. Ancestral polymorphism

What happens depends on Ne!

1. Ancestral polymorphism

t 2

Tim

e

t 1

Likelihood of non-phylogenetic lineage sorting:

1.  Residence time (Ne)

2.  Time between successive splitting events (t)

Other terms:

1.  Lineage sorting

2.  Incomplete lineage sorting

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2. Birth-death evolution in gene families

Tandem array of 2 genes in the ancestral species

(−)

(−)

(+)

(+)

(+)

(−) (−)

1 2

A1 A2 B1 B2 C1 C2

Gene “Birth”: (+)Gene “Death”: (-)

time

Tandem array of 2 genes in the ancestral species

(−)

(−)

(+)

(+)

(+)

(−) (−)

1 21 2

A1 A2A1 A2 B1 B2B1 B2 C1 C2C1 C2

Gene “Birth”: (+)Gene “Death”: (-)

time

A B C

A1 B1 C1

Species tree

Gene (1) tree

A B C

A1 B1 C1

Species tree

Gene (1) treeSpecies A Species B

Species C

Gene 1 Gene 2

3. Trans-species evolution

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3. Recombination

A B C D

a b c d

A B C D

a B C d

Gene conversion between the same gene

A B

a b

a B

A b

Parental contribution Resultant offspring

Gene conversion between different genes

Gene A Gene A Gene A

Gene B

Among alleles within an individual: think about patterns of population coalescence

Among alleles within an individual: this is a nonreciprocal exchange

Among genes (paralogs) within an individual: this is also a nonreciprocal exchange. Remember that different genes can have different phylogenetic histories

4. Lateral gene transfer (LGT)

time

a b c

A B C

a b c

Species tree

Gene tree

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Organism history can different from gene history

Selected examples (in notes):

•  Birth-death evolution in gene families

•  Trans-species evolution •  Recombination

•  Lateral gene transfer (LGT)

Other sources:

•  Statistical error

•  Human error

Human error: What happens if you mistake paralogous genes for orthologous genes?

Mus

Cricetinae

Homo

Gallus Sceloporus

Rattus

Sus Homo

Sus

Rabbit Mus Rattus

Ldh - A

Ldh - C Gene duplication

event Ldh–A gene to infer the relationships of mammals:

Data set:

Mus (Opps! Ldh-C)

Sus (Ldh-A)

Homo (Ldh-A)

Rabbit (Ldh-A)

Rattus (Ldh-A)

Gallus (Ldh-A)

Sceloporus (Ldh-A)