1. 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

2. Homeotic Genes Genes in which a mutation can transform one body segment into another segment Commonly known as Hox genes They are transcription factors

4. 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.

5. Homeobox -containing protein bound to DNA

6. Exon 1 Exon 2Exon 3 Cis- and trans-regulators of gene expression Transcription cis-element (6-10 nucleotides) Transcription factor

7. Hox genes and Drosophila body plan Sean Carroll

8. Sean Carroll’s lab

10. 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

11. 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

12. 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

13. Human and mouse 9 Pax genes: Pax-1 to -9 Drosophila Paired, gooseberry, gooseberry neuro, pox meso, pox neuro, eyeless, sparkling

14. Paired domain Octapeptide Octapeptide Homeodomain Homeodomain Pax-1Pax-9 Pax-2Pax-5Pax-8 Pax-3Pax-7 Pax-4Pax-6

15. Expression Patterns Pax-1 vertebral column and thymus Pax-9 vertebral column Pax-2 neural tube and hind brain, excretory system ear and eye excretory system ear and eye Pax-5 brain, neural tube, liver cells giving rise to B lymphocyte rise to B lymphocyte Pax-8 neural tube, hind brain, excretory system, thyroid system, thyroid

16. Expression Patterns Pax-3 neural tube, dermomytome and limb bud, cranio-facial limb bud, cranio-facial structure structure Pax-7 brain, neural tube, dermomyotome Pax-4 pancreas Pax-6 brain, neural tube, nose, eye, pancreas pancreas

17. Pax-2 defects in kidney optic nerve, retina optic nerve, retina Pax-3 neural crest defects Pax-6 small eye Mutations in mouse can cause

19. 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.

21. 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!

22. 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

24. 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.

25. Conclusions (1) A gene duplicate can become nonfunctional and eventually disappear from the genome.

26. 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

27. Thanks!