Homology

Homology Review

Human armLobed-fin fish finBat wing Bird wing

Insect wing

Homologousforelimbs

not homologous as forelimbs or wings

Definition: Structures (including genes) are homologous if they evolved from some structure in a common ancestor

Wings are functionally classified, and are analagous structures

not homologous as wings

Which of the following structures are homologous?

Why do we care about homology when building an anatomy ontology?

Consider an anatomy ontology of vertebrates:

skeletal systemcranial skeletal system

parietal bone (in_organism human)parietal bone (in_organism zebrafish) frontal bone (in_organism human)frontal bone (in_organism zebrafish)

Homologous : frontal bone (zebrafish) and parietal bone (human)

fpa

Different genes and developmental processes may underlie the development of the zebrafish frontal and the human frontal, even

though they have the same name and are similarly located

Homologous_toA1 in B1 homologous_to A2 in B2

iff

exists A3, B3:

A1 in B1 descends_from A3 in B3

&

A2 in B2 descends_from A3 in B3

(Note B1 and B2 must both be subclades of the clade descending* from D)

(*In the genealogical sense)

Note: Do we need to include time (exists & existed)? FN – just to be on the safe side we can include time – it's not useful but it could stop the some people complaining and it won't affect the logic at all.[edit] relation to what is in RO proposed

Directly_descends_from

x1 directly_descends_from x2 iff there are y1, y2 such that:

- y1 is an organism

- x1 is an anatomical structure

- x1 part_of y1

- y2 is an organism

- x2 is an anatomical structure

- x2 part_of y2

- y2 is a parent of y1

-the genetic sequence that determined the morphology of x1 is partially a copy of the genetic sequence that determined the morphology of x2.

descends_from is the instance level relation which is the transitive closure over directly_descends_from

Descends_from

A in B descends_from C in D :

For all A(a) -> exists b, d, c: B(b) & C(c) & D(d)

a part_of b

a descends_from c

c part_of d

(Note – B must be a subclade of the clade descending* from D)

Note that there are a number of synonyms for descended_from, including 'evolutionarily_derived_from' which is currently in ROproposed as follows:

id: OBO_REL:evolutionarily_derived_from

name: evolutionarily_derived_from

def: "Instance 3-ary relation: x edf y as T iff x specified_by gx and gx ancestral_copy_of gy and gy specifies y" []

synonym: "derived_from" RELATED []

synonym: "descended_from" RELATED []

synonym: "evolved_from" RELATED []

is_transitive: true

What are Characters?

a,b - symphysial bone margins straight

c - anterior symphysial bone margin concave, resulting in oval gap between bone halves

Character “optimization”

• Method to infer ancestral conditions (features)– Inferred ancestral condition dependent on

phylogenetic tree– I.e. different trees may imply differently

reconstructed ancestors

Ancestral uncertainty

A B C DSpeciesFeature + + --

+/-

+/-

+/-

Tree #1

+

+

E

Ancestral certainty

A BC DSpeciesFeature + + --

+/-

+/-

+

Tree #2

+E

-

I. Bilaterians

Phylogeny from Garey, 1999

+

+

+

+/-

+/- ___

__

__

_

_

_

_

___

__

_

__

___

_

_+

++++/-

+/-+/-

_

_

__

_

_

_

_

_

_

NoNo heart

in ancestor of Bilateria

Heart presence/absence optimized on Bilaterian tree

Character Optimization

• Tree - including an ‘out group’

• Character Matrix - states for taxa at tips of tree

• Assign values from column of matrix to tree

• ‘Polarize’ the state at the root using the outgroup

Homology Evidence Codes

• Inferred from morphological similarity

• Inferred from positional similarity

• Inferred from developmental similarity

• Inferred from compositional similarity

• Inferred from gene expression similarity

• Inferred from phylogeny

How and where should homology information be captured?

Homology between genes is already determined and recorded by the model organism community

Use case: Query for phenotypes affecting the human frontal bone and its homologous structure in other species.

Homologs = Synonyms

Gene homology

Types of gene homology:

•Genes that diverged due to a speciation event are termed orthologs• Genes that diverged due to a duplication within a species are termed paralogs

Gene orthology is recorded using different types of evidence:

mouse

Conserved location:

Kim et al., 1999

FuguA

HOXB

Each homology assignment is associated with reference to a physical piece of evidence, a person, or literature.

Homology assignments are based on specific kinds of evidence IP: Inferred from Position ID: Inferred from Development IC: Inferred from Composition

Homology statements include evidence and citations, and different homology statements are used to create and refine phylogenies.

Homology between anatomical structures is already determined and but not yet captured in a database the evolutionary community

Homologous structures are already implicit within MODs ontologies

1. Do we need a relationship in OBO-REL to define homology? This is a symmetric relation between sisters and it is the relationship that requires evidence and attribution.

2. Should homology assignments be a top-down or bottom up approach?eg. Pairs of taxa vs. CARO-centric assignments? RE:domain experts are required. It might be easier to enlist help in a pairwise manner.

3. Homology needs to be captured for similarity searches. Text or synonym searches are insufficient. Does CARO take into account homology or is it a separate data set?

4. If two structures are deemed homologous, how does this information transfer down is_a chains? Need use cases.

Discussion points

Entity (AO): Ceratobranchial 5 teethAttribute (PATO): Is_present

Entity (AO): Ceratobranchial 5 teethAttribute (PATO): Is_absent