Homologous genes are genes that have descended from a common ancestral gene. There are two main types of homologous genes: 1. Orthologous genes are homologous genes in different species that arose due to speciation. For example, the human and mouse eyeless genes are orthologs that descended from the eyeless gene in their last common ancestor. 2. Paralogous genes are homologous genes within the same species that arose due to a gene duplication event. For example, the fruit fly eyeless and twin of eyeless genes are paralogs that descended from a duplication of the eyeless gene in a fruit fly ancestor. Homologous genes can differ in their sequences due

1. Homology
Dr Avril Coghlan
alc@sanger.ac.uk
Note: this talk contains animations which can only be seen by
downloading and using ‘View Slide show’ in Powerpoint

2. Homologues
• Slightly different versions of the eyeless gene control
eye formation in many animals
• eyeless genes in different animals are homologues
ie. they are homologous (related) genes that descended from an
ancestral gene in the ancestor of all these animals
Human eyeless Controls human
(PAX6 or aniridia) eye development
ancestral eyeless Controls mouse
gene Mouse eyeless eye development
Tiger eyeless Controls tiger eye
development
Sea squirt eyeless Controls sea squirt
Note: the ancestral eyeless eye development
gene may not have been Drosophila eyeless Controls fruitfly
involved in eye formation eye development

3. • Aside: this is a phylogenetic tree of eyeless genes in
different animals
A representation of the evolutionary relationships between
members of the eyeless gene family
External nodes represent existing genes in different species
Internal nodes represent their ancestors (usually extinct)
100s of millions of The present
years ago
Human eyeless
(PAX6 or aniridia)
Mouse eyeless
Tiger eyeless
ancestral eyeless
gene Sea squirt eyeless
Time Drosophila eyeless

4. Types of homology
• Walter Fitch (1970) realised that there are different
types of homologues
• Orthologues are homologues in different species that
arose due to the speciation event
Human eyeless
Mouse eyeless
Tiger eyeless
Time
Sea squirt eyeless
an internal node (ancestor) Fruitfly twin of eyeless
an external node (existing gene) Fruitfly eyeless

5. Types of homology
• Walter Fitch (1970) realised that there are different
types of homologues
• Orthologues are homologues in different species that
arose due to the speciation event
Speciation event giving rise to human and mouse
eyeless in the human-mouse ancestor Human eyeless
Mouse eyeless
The human and mouse eyeless genes
Tiger eyeless
are orthologues
Time
Sea squirt eyeless
an internal node (ancestor) Fruitfly twin of eyeless
an external node (existing gene) Fruitfly eyeless

6. • Paralogues are homologues that arose due to a gene
duplication event within a species
Human eyeless
Mouse eyeless
Tiger eyeless
The fruitfly eyeless and twin of
Sea squirt eyeless
eyeless genes are paralogues
Time Fruitfly twin of eyeless
Fruitfly eyeless
an internal node (ancestor)
an external node (existing gene)
Duplication event giving rise
eyeless in a fruitfly ancestor to twin of eyeless

7. Types of homology
• Homologues (homologous genes) are genes that
derive from a common ancestor-gene
• Orthologues (orthologs) are homologous genes in
different species
• Paralogues (paralogs) are homologous genes in one
species that derive from gene duplication
When one gene is duplicated, the duplication event results in two paralogous
genes (paralogues)
Studies of paralogs have found that one paralogue of a pair often retains the
ancestral gene’s function, while the other paralogue is free to
evolve and adopt new functions
Ancestral gene Duplication event Paralogue 1 Paralogue 2

8. Evolution of homologues
• Homologues can differ because of mutations that
occurred since their common ancestor
Substitution of one nucleotide for another eg.
Mouse eyeless
eyeless in the human- gene
mouse ancestor ACTGTA...
ACTGTA...
Human eyeless
T→C
sub stitut gene
io n ACTGCA...
Speciation event giving rise to human and mouse

9. Insertion of nucleotides eg.
eyeless in the human- Mouse eyeless
mouse ancestor ACTGTA...
ACTGTA...
Insert Human eyeless
ion of
G
AGCTGTA...
Deletion of nucleotides eg.
eyeless in the human- Mouse eyeless
mouse ancestor T ACGTA...
ion of
ACTGTA... Delet
Human eyeless
ACTGTA...

10. • Comparing 2 sequences, we don’t know the
ancestor’s sequence, so can’t tell in which species an
insertion/deletion (indel) occurred
eg. mouse ACTGTA... and human ACTGGTA...
They may have evolved by an insertion in human:
eyeless in the human-
mouse ancestor
Mouse eyeless
ACTGTA... ACTGTA...
Insertion of G ACTGGTA...
Human eyeless
Alternatively, they may have evolved by a deletion in mouse:
eyeless in the human-
mouse ancestor
Mouse eyeless
ACTGGTA...
D eletion of G ACTGTA...
ACTGGTA...
Human eyeless

11. Further Reading
• Chapter 3 in Introduction to Computational Genomics Cristianini & Hahn