Transcript Determinants of Gene Duplicability

Chemosensory receptors
Chemoreceptors include olfactory
receptors. They all have 7
transmembrane domains and form the
largest super gene family in animals.
No. of chemoreceptor genes:
Nematode: ~1220
Fruitfly:
~170
Homeotic Genes
Genes in which a mutation can
transform one body segment into
another segment
Commonly known as Hox genes
They are transcription factors
A homeotic mutation in Drosophila: Disruption of a Hox
gene can lead to a phenotype known as Antennapedia in
which fly legs develop in place of the antennae.
Homeobox
-containing
protein
bound to
DNA
Cis- and trans-regulators of
gene expression
Transcription
factor
Transcription
Exon 1
cis-element
(6-10 nucleotides)
Exon 2
Exon 3
Hox genes
and
Drosophila
body plan
Sean Carroll
Sean Carroll’s lab
Observations
• The vertebrate genes homologous
to fly homeotic genes are found in
four clusters, tightly linked.
• Vertebrate Hox genes are expressed
in the same anterior-posterior
order along the body axis as in flies
Implications
• The homeobox regulatory gene
clusters date to ancestors that
predate the arthropod-vertebrate
divergence ~600 million years ago
• Humans and mice aren’t so
different from flies in body-plan
development
Pax Genes
Defined by the presence of a
conserved paired-box that codes for a
128-amino-acid paired domain, a
DNA binding domain
Encode nuclear transcription factors
involved in developmental control,
notably the central nervous system
Human and mouse
9 Pax genes: Pax-1 to -9
Drosophila
Paired, gooseberry, gooseberry neuro,
pox meso, pox neuro, eyeless, sparkling
Paired domain Octapeptide Homeodomain
Pax-1
Pax-9
Pax-2
Pax-5
Pax-8
Pax-3
Pax-7
Pax-4
Pax-6
Expression Patterns
Pax-1
Pax-9
vertebral column and thymus
vertebral column
Pax-2
neural tube and hind brain,
excretory system ear and eye
brain, neural tube, liver cells giving
rise to B lymphocyte
neural tube, hind brain, excretory
system, thyroid
Pax-5
Pax-8
Expression Patterns
Pax-3 neural tube, dermomytome and
limb bud, cranio-facial
structure
Pax-7 brain, neural tube, dermomyotome
Pax-4 pancreas
Pax-6 brain, neural tube, nose, eye,
pancreas
Mutations in mouse can cause
Pax-2
defects in kidney
optic nerve, retina
Pax-3
neural crest defects
Pax-6
small eye
An additional
eye on the
antenna
induced by
targeted
expression of
mouse Pax 6
Halder, G., Callaerts,
P. and Gehring, W.J.
(1995). Induction
of ectopic eyes by
targeted expression
of the eyeless gene
in Drosophila.
Science 267, 17881792.
Pax 6 in mammals vs.
eyeless in fruitflies
• The two proteins have highly
similar paired domains.
• Mouse Pax 6 gene can induce eye
development in Drosophila, despite
more than 600 million years of
separation!
Despite great differences in eye
type, Drosophila and human use
Pax 6 to control eye development!
Loss of duplicate genes
• A duplicate gene can become
nonfunctional (a pseudogene) if there
is no advantage to keep it.
• Indeed, there are pseudogenes in
every eukaryotic genome studied.
Example:
Globin pseudogenes in human
Many chemoreceptor pseudogenes
• In nematode: ~1220 functional genes
but 419 pseduogenes
• In mouse: ~ 1000 olfactory receptor
(OR) genes
In human only ~400 OR genes
Reason: There are many more OR
pseudogenes in human than in
mouse.
Conclusions (1)
A gene duplicate can become
nonfunctional and eventually
disappear from the genome.
Conclusions: Gene duplication can
•
•
•
•
•
Meet a large dosage requirement
Lead to fine-tuning of cell physiology
Provide functional expansion
Provide functional diversification
Provide raw materials for the
emergence of novel function
• Has led to evolution of body plan in
animals
• Has led to the evolution of the central
nervous system in animals
Thanks!