1. Chapter 19 Comparative Genomics and the Evolution of Animal Diversity

2. ✣ Author : 倪佩兰 ✣ Number: 200332550042 ✣生物科学类 1 ＞ Group8

3. OUTLINE  Three ways gene expression is changed during evolution.  Most animal have essentially the same genes.  Experimental manipulations that alter animal morphology.  Morphological changes in crustaceans and insects.  Genome evolution and human origins.

4. Preface of this chapter  Charles Darwin: all animals arose from a common ancestor.  There are 25 different animal phyla, but where did evolutionary diversity come?  Animal phyla includes :ecdysozoans,. lophotrochozoans, deuterostomes.  Different genomes offer the promise for diversity.

5. Figure 19-1 Summery of phyla

6. Figure 19-2 Phylogeny of assemble d genomes

7. Topic1: Most Animals Have Essentially the Same Genes  A striking factor: different animals have essentially the same genes (human, pufferfish and mice are similar in genome).  The genetic conversion seen among vertebrates extends to Ciona intestinalis.  Increase in gene number in vertebrates is due to the duplication of genes already present in the ecdysozoans rather than the invention of entirely new genes.

8. Figure 19-3 Phylogenetic tree show gene duplication of the fibroblast grouth factor genes

9. ✰ How does gene duplication give rise to biological diversity? Two models for how duplicated genes can create diersity: ❶ An ancestral gene produce multiple genes via duplication,and the coding regions of the ew genes undergo mutation. ❷The duplicated genes do not take on new functions,but instead acquire new DNA sequences.

10. Box19-1 The structures of the genes coding the Gsb and Prd proteins

11. Box19-2 Duplication of β-Globin gene family in the evolution of vertebrates

12. Topic2:Three Ways Gene Expression Is Changed During Evolution ❶A given pattern determining gene can itself be expressed in a new pattern (this will cause those genes whose expression it controls to aquire new patterns of expression).( Figure19- 4a) ❷The regulatory protein encoded by a pattern determining gene can aquire new functions. ).( Figure19-4b) ❸Target pattern of a given pattern determining gene can acquire new regulatory DNA sequences, and thus come under the control of a different regulatory gene. ( Figure19-4c)

13. Figure19-4 Summery of the three strategies for altering the roles of pattern determining genes

15. Topic3:Experimental Manipulations That Alter Animal Morphology  The first pattern determining gene was identified in Drosophila in the Morgan Fly.Lab  During the past 20 years,a variety of manipulations have document the importance of several pattern determining genes in development.

16. ⅰ Changes in Pax6 expression create ectopic eyes  Pax6 Pax6 is the most notorious pattern determining gene.  Normally Pax6 express within developing eyes, but mistake appears, Pax6 causes the development of extra eyes.  Altered expression of Pax6 has been correlated with the formation of eye spot.  Pax6 genes from other animals also produce ectopic eyes when mixexpressed in Drosophila.. ⅱ

17. Figure19-5 Misexpression of Pax6 and eye formation in Drosophila

18. ⅱ Changes in Antp Expression Transform Antennae into Legs  Antp is a second Drosophila pattern determining gene which contril the development of the middle segment of the thorax,the mesothorax.  Antp encodes a homeodomain regulatory protein that is normally expressed in the mesothorax of the developing enbryo.  When misexpressed in the head, Antp causes a striking change: legs develop instead of antennae.

19. Figure19-6 A dominant mutation in the Antp geene results in the homeotic transformation of antennae into legs

20. ⅲ Importance of protein transform Antennae into legs  Pattern determining genes need not be expressed in different places to produce changes in morphology.  Example: two relared pattern deternmining genes in Drosophila :ftz and Antp.

21. Figure19-7 Duplication of ancestral gene leading to Antp and ftz

22. ⅳ Subtle Changes in an enhancer sequence can produce of gene expression  Enhancers with high-affinity sites are expressed in the neurogenic ectoderm.  The enhancer contains two low-affinity Dorsal binging sites,and is activate by high levels of the Dorsal gradient in ventral regions.  Dorsal functions synergisticaly with another transcripton factor Twist to activate gene expression in the neurogenic ectoderm.  So the enhancers can evolve quickly to create new patterns of gene expression.

23. Figure19-8 Regulation of transgene expression in the early Drosophila embryo

24. ⅴ The misexpression of Ubx changes the morphology of the fruit fly  New patterns of gene expression are produced by changing the Ubx expression pattern, or its target enhancers.  Ubx encodes a homeodomain regulatory protein  In figure 19-9b, Ubx mutants exhibit a spectacular phenotype: fly with four fully developed wings.  In figure 19-10, the Cbx mutation causes Ubx to be misexpressed in the mesothorax; and Ubx now represses the expression of Antp and some other genes.. As a result, in figure 19-10, Cbx mutant flies look like wingless ants.

25. Figure19-9 Ubx mutants cause the transformation of the metathorax into a duplicated mesothorax

26. Figure19-10 Misexpression of Ubx in the mesothorax results in the loss of wings

27. ⅵ Changes in Ubx modify the morphology of Fruit Fly embryos  Ubx functions as a repressor, and the Ubx protein contains specific sequences that recruit repression complexes.  Transgenic fly embryos have been create that either the Antp or Ubx protein coding sequence under the control of the hsp70 heat shock regulatory DNA.  Ubx normally functions as a repressor.

28. Figure19-11 Changing the regulatory activities of the Ubx protein

29. ⅶ Changes in Ubx target enhancers can alter patterns of gene expression  Ubx binds DNA as a Ubx-Exd dimer similarly to Antp.  Many homeotic regulatory proteins interact with Exd and binds a composite Exd-Hox recongnition sequence.  Ailering the function or expression of Ubx or its target enhancers changes patterning in the Drosophila embryos and adults.

30. Figure19-12 Interconve-rsion of labial and Ubx binding sites

31. Box19-4-1 Orgnization and expression of Hox genes in Drosophilla and in the mouse

32. Box19-4-2 Conservation of orgnization and expression of homeotic gene complexes in Drosophilla and in the mouse

33. Box19-4-3 Partial transformation of the first lumbar vertebra in a mutant mouse embryo

34. Topic4:Morphological Changes In Crustaceans And Insects  Three strategies for altering the activities of pattern determininggenes.  The first two,changes in the expression and function of pattern determining genes, explain changes in limb morphology seen in certain ctastaceans and insects.  The third, changes in regulatory sequences, explain different patterns of wing development in fruit flies and butterflies.

35. ⅰArthropods are remarkably diverse  Arthropods embrace five groups: trilobites, hexapods, crustaceans, myriapods, and chelicerates.  The success of the arthropods derives from their modular architecture.  These organisms are com[osed of a series of repeating body segments that can be modified in seemingly limitless ways.

36. ⅱ Changes in Ubx expression modifications in limbs among the crustaceans  Artemia,a group of crustaceans, is most studied.  Slightly different patterns of Ubx expression are observed in branchiopods and isopods.  Explanation: the Ubx regulatory DNA of isopods acquired mutations.

37. Figure 19-13 Changing mophologi-es in two different groups of crustaceans

38. ⅲ Why insects lack abdominal limbs  The loss of abdominal limbs of insects is due to functional changes in the regulatory protein.  In crustaceans, there are high levers of both Ubx and Dll in all 11 thoracic segment.  The drosophila Ubx protein is functionally distinct from Ubx in crustacean. In contrast with fly, the crustacean protein has a short motif containing 29 amino acid residues that block repression activity.  Both the crustacean and fly proteins contain multiple repression genes. ⅲ

39. Figure19-14 Evolutionary changes in Ubx protein function

40. Figure19-15 Comparison of Ubx in crustaceans and insects

41. ⅳ Modification of flight limbs might arise from the evolution of regulatory DNA sequences  In Drosophila, Ubx is expressed in the developing halteres where it functions as a repressor of wing developed.  All members of dipterans contain a sinder pair of wings and a set of halteres.  The two olders diverged from a common ancestor more than 250 million years ago.  Reason for different wing morphologies: changes in the regulatory sequences of several Ubx targrt genes.

42. Figure19-16 Changes in the regulatory DNA of Ubx targrt genes

43. Box19-5-1 Distalless expression in various animal embryos

44. Box19-5-2 The expression of Dll and other pattern determining genes inthe eyespot ofβ.anynana

45. Topic5:Genome Evolution and Human Origins ⅰHumans contain surprisingly few genes  The human genome contain only 25000---30000 protein coding genes.  The higher vertebrates contain sophisticated mechanisms for gene regulation in order to produce many patterns of gene expression.  Fruit flies is more complex than the worm from an increase in the number of gene expression patterns.

46. ⅱ The human genome is very similar to the mouse and the chimp  Mice and human contain roughly the same number of genes---about 28000 protein coding genes.  The chimp and human genomes are even more highly conserved.

47. ⅲ The evolutionary origins of human speech  One of the defining features of being human-- --speech.  Speech depends on the precise coordination of the small muscles in our larynx and mouth  Human ’ s FOXP2 protein is unique: T to N at position 303 and N to S at position 325.  Changes in the exprssion pattern of or changes in FOXP2 target genes might promote speech in humans. ⅲ

48. Figure19-17 Summery of amino acid changes in the FOX2 proteins of mice and primates

49. Figure19-18 Comparison of the FOX2 gene sequences in human, chimp and mouse

50. ⅳ How FOXP2 fosters speech in humans  Changes in the FOXP2 regulatory DNA might cause the gene to acquire a new pattern of gene expression in the human being.  Perhaps these changes have augmented the levels or timing of gene expression, so critical signals are active in the larynx when effected to language.  It is difficult to estimate the number of “ speech regulatory genes ” evolved in humans. ⅳ

51. Figure19- 19 A scenario for the evolution of speech in humans

52. ⅴ The future of comparative genome analysis  It is impossible to infer the function of roughly half of all predicted protein coding genes based solely on primary DNA sequence information.  There is also a glaring limitation to infer the function of regulatory DNA from simple sequence inspection.  In the future it might e possible to identify changes in the expression profiles of homologous genes. ⅴ

53.  That is all for Chapter 19.  Thank you for appreciation!