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

Exon 1 Exon 2 Exon 3

Cis- and trans-regulators of gene expression

Transcription

cis-element(6-10 nucleotides)

Transcription factor

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 Pax GenesGenes

Defined by the presence of a Defined by the presence of a conserved paired-box that codes for conserved paired-box that codes for a 128-amino-acid paired domain, a a 128-amino-acid paired domain, a DNA binding domainDNA binding domain

Encode nuclear transcription factors Encode nuclear transcription factors involved in developmental control, involved in developmental control, notably the central nervous systemnotably the central nervous system

Human and mouseHuman and mouse

9 Pax genes: 9 Pax genes: Pax-1 to -9Pax-1 to -9

DrosophilaDrosophila

Paired, gooseberry, gooseberry neuro, Paired, gooseberry, gooseberry neuro, pox meso, pox neuro, eyeless, sparklingpox meso, pox neuro, eyeless, sparkling

Paired domain Paired domain Octapeptide Octapeptide HomeodomainHomeodomain

Pax-1 Pax-1 Pax-9 Pax-9

Pax-2Pax-2Pax-5 Pax-5 Pax-8Pax-8

Pax-3Pax-3Pax-7Pax-7

Pax-4Pax-4Pax-6Pax-6

Expression PatternsExpression Patterns

Pax-1 Pax-1 vertebral column and thymusvertebral column and thymusPax-9 Pax-9 vertebral columnvertebral column

Pax-2 Pax-2 neural tube and hind brain, neural tube and hind brain, excretory system ear and eyeexcretory system ear and eyePax-5 Pax-5 brain, neural tube, liver cells giving brain, neural tube, liver cells giving rise to B lymphocyterise to B lymphocytePax-8 Pax-8 neural tube, hind brain, excretoryneural tube, hind brain, excretory system, thyroidsystem, thyroid

Expression PatternsExpression Patterns

Pax-3 Pax-3 neural tube, dermomytome and neural tube, dermomytome and limb bud, cranio-facial limb bud, cranio-facial structurestructurePax-7 Pax-7 brain, neural tube, dermomyotomebrain, neural tube, dermomyotome Pax-4 Pax-4 pancreaspancreasPax-6 Pax-6 brain, neural tube, nose, eye, brain, neural tube, nose, eye, pancreaspancreas

Pax-2 Pax-2 defects in kidneydefects in kidney optic nerve, retinaoptic nerve, retina

Pax-3 Pax-3 neural crest defectsneural crest defects

Pax-6 Pax-6 small eyesmall eye

Mutations in mouse can causeMutations in mouse can cause

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, 1788-1792.

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!