Homology
Homology Review
Which of the following structures are homologous?
Definition: Structures (including genes) are homologous if they
evolved from some structure in a common ancestor
Homologous
forelimbs
not
homologous
as forelimbs
or wings
Human arm
Lobed-fin fish fin
Bat wing
Bird wing
not
homologous
as wings
Insect wing
Wings are functionally classified, and are analagous structures
Why do we care about homology when building an
anatomy ontology?
Consider an anatomy ontology of vertebrates:
skeletal system
cranial skeletal system
parietal bone (in_organism human)
parietal bone (in_organism zebrafish)
frontal bone (in_organism human)
frontal bone (in_organism zebrafish)
f
pa
Homologous : frontal bone (zebrafish) and parietal bone (human)
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_to
A1 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 usefu
[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
Species
Feature
A
+
B
-
C
+
D
+
E
+/-
+/-
+
Tree #1
+/-
Ancestral certainty
Species
Feature
A
+
C
+
B
-
D
+
E
+/-
Tree #2
+/-
+
Heart presence/absence optimized on Bilaterian tree
+
+
+/+
_
+/No heart
+/+_
in ancestor
No
+/+_
of Bilateria
_
_ _
_
_
_
_
_
_
_ _
_
+
_
_
_
+/_
_
_
+
__
_
_
_
_
_
_
_
_
__
_
I. Bilaterians
Phylogeny from Garey, 1999
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
Use case: Query for phenotypes affecting the
human frontal bone and its homologous
structure in other species.
Homologs = Synonyms
How and where should homology information be
captured?
Homology between genes is already determined and
recorded by the model organism community
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:
FuguA
Conserved location:
HOXB
mouse
Kim et al., 1999
Homology between anatomical structures is already
determined and but not yet captured in a database
the evolutionary community
Homology assignments are based on specific kinds of
evidence
IP: Inferred from Position
ID: Inferred from Development
IC: Inferred from Composition
Each homology assignment is associated with reference to a
physical piece of evidence, a person, or literature.
Homology statements include evidence and
citations, and different homology statements are
used to create and refine phylogenies.
Homologous structures are already implicit within MODs ontologies
Discussion points
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.
Entity (AO): Ceratobranchial
5 teeth
Attribute (PATO): Is_present
Entity (AO): Ceratobranchial 5
teeth
Attribute (PATO): Is_absent