Chemosensory receptors Chemoreceptors include olfactory receptors They all

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 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 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!