Chapter 19 Comparative Genomics and the Evolution of Animal Diversity

1. Chapter 19 Comparative Genomics and the Evolution of Animal Diversity • Most animals have essentially the same genes • Three ways gene expression is changed during evolution • Experimental manipulations that alter animal morphology • Morphological changes in crustaceans (甲殼類動物) and insects • Genome evolution and human origins

2. Fig 19-1 summary of phyla (門) Phyla: a basic type of animal Bilaterians: deuterosomes 後口動物 lophotrochozoans ectysozoans

3. Whole-genome sequence information is now available for both ecdysozoans (fruit fly, nematode worm) and deuterostomes (mouse, puffer fish, zebrafish).

4. Fig 19-2 phylogeny 系統發生學of assembled genome

5. Most animals have essentially the same genes • Pufferfish, mice, and humans-each contain about 30,000 genes. With very few exceptions, about every human gene has a clear counterpart in the mouse genome. • The increase in gene number in vertebrates is mainly due to duplications of genes already present in ecdysozoans, rather than the invention of entirely new genes.

6. Fig 19-3 phylogenetic tree showing gene duplication of the fibroblast growth factor genes (FGFs). Ciona FGFs: orange; 6 Vertebrate FGFs: black; 22 Each gene in the sea squirt duplicated into an average of four copies in vertebrates.

7. How does gene duplication give rise to biological diversity? • Gene duplications give rise to related proteins with slightly different functions through mutations • Duplicated genes do not necessarily take on new functions, but instead take on new regulatory DNA sequences, and the genes are expressed in different patterns

8. Box 19-2 Duplication of globin genes produce new expression patterns and diverse protein functions.

9. Three ways gene expression is changed during evolution • Pattern determining genes: cause the correct structure to develop, but in the wrong place, when they are misexpressed in development eg. Pax6 The average animal genome contain about 1,000 kinds of regulatory genes, and about 100 are pattern-determining genes

10. Three strategies for altering the activities of pattern-determining genes • Pattern-determining gene itself be expressed in a new pattern • Protein encoded by a pattern-determining gene can acquire a new function • Target gene of a pattern-determining gene acquire new regulatory DNA sequences

11. Fig 19-4 three strategies for altering the roles of pattern determining genes

12. Experimental manipulations that alter animal morphology

13. Change in Pax6 expression create ectopic eyes Fig 19-5 Misexpression of Pax6 (also called ey) and eye formation in Drosophilla.

15. Changes in Antp (Antennapedia) expression transform antenna into legs Fig 19-6 A dominant mutation in the Antp gene results in the homeotic transformation of antennae into legs

16. Importance of protein function: interconversion of ftz and antp Figure 19-7 Duplication of ancestral gene leading to Antp and ftz

17. Subtle changes in an enhancer sequence can produce new patterns of gene expression

18. Fig 19-8 Regulation of transgene expression in the early Drosophila

19. The misexpression of Ubx changes the morphology of the fruit fly • Ubx: encodes a homeodomain regulatory protein that controls the development of the third thoracic segment, the metathorax • Ubx represses Antp and restricts Antp expression to be in the second thoracic segment, the mesothorax.

20. Fig 19-9 Ubx mutants cause the transformation of the metathorax into a duplicated mesothorax Ubx represses Antp in the metathorax and restricts the expression of Antp to mesothorax. In Ubx mutants, Antp is expressed in both mesothorax and metathorax, and therefore the metathorax is transformed into a mesothorax.

21. Fig 19-10 Misexpression of Ubx in the mesothorax results in the loss of wings The Cbx mutation disrupts the regulatory region of Ubx, causing its misexpression in the mesothorax and results in its transformation into the metathorax.

22. Changes in Ubx function modify the morphology of fruit fly embryos • Ubx protein can function as a transcriptional repressor that precludes the expression of Antp and other mesothorax genes in the developing metathorax. • Conversion of Ubx into a transcriptional activator causes it to function like Antp and promote the development of mesothorax.

23. Fig 19-11 Changing the regulatory activities of the Ubx protein.

24. Changes in Ubx target enhancers can alter patterns of gene expression Fig 19-12 Interconversion of Labial and Ubx binding site Lab is a Hox protein that controls the development of anterior head structure.

25. Morphological changes in crustaceans and insectsArthropods 節肢動物門 are remarkably diverse • Trilobites三葉蟲(extinct) • Hexapods 六足蟲 (such as insects) • Crustaceans 甲殼類 (shrimp, lobster, crabs etc) • Myriapods 多足類 (centipedes 蜈蚣, millipedes 千足虫) • Chelicerates 螯肢節肢動物 (horseshoe crabs, spiders, scorpions)

26. Changes in Ubx expression explain modifications in limbs among the crustaceans Fig 19-13 changing morphologies in two different groups of crustaceans. In branchiopods Scr expression is restricted to head regions where it help promote development of feeding appendage. In isopods, Ubx is missing in T1 and so Scr is expressed in both head segment and T1. Swimming limb in T1 is thus transformed into a feeding appendage.

27. During the divergence of branchiopods and isopods, the Ubx regulatory sequences changed in isopods. The Ubx gene is not expressed in T1, therefore Scr is expressed in T1 and cause the development of maxillipeds.

28. Why insects lack abdominal limbs? • The loss of abdominal limbs in insects is due to functional changes in the Ubx regulatory protein. • In insects, Ubx and abd-A repress the expression of Distalless (Dll) in first seven abdominal limbs.

29. Fig 19-14 Evolutionary changes in Ubx protein function. • Dll enhancer is normally activated as 3 spots in drosophila embryos. • (b) Missexpression of Drosophila Ubx in these 3 spots cause the reduction of Dll expression • (c) Missexpression of artemia Ubx in the three spots does not decresase Dll expression,

30. Fig 19-15 Comparison of Ubx in crustaceans and in insects.

31. Modifications of flight limbs might arise from the evolution of regulatory DNA sequences Fig 19-16 Changes in the regulaotry DNA od Ubx target genes. The Ubx repressor is expressed in the halteres of dipterans and hindwings of lepidopterans.

32. Genome evolution and human origins • Humans contains surprisingly few genes: 25,000-30,000 Organismal complexity is not correlated with gene number, but instead depends on the number of gene expression patterns.

33. Nematodes: gene number 20,000 patterns of gene expression 30,000 • Drosophila: gene number 14,000 patterns of gene expression 50,000

34. The human genome is very similar to that of the mouse and virtually identical to the chimp • There are very few “new” genes in humans that are completely absent in mice.

35. The evolutionary origins of human speech Speech depends on the precise coordination of the small muscles in our larynx and mouth. Reduced levels of a regulatory protein called FOXP2 cause severe defects in speech. Afflicted individuals exhibit difficulties in articulation. Potential target genes of the FOXP2 regulatory proteins might encode neurotransmitters or other critical signals in the developing larynx.

36. Fig 19-17 summary of amino acid changes in the FOXP2 proteins of mice and primates.

37. Fig 19-18 Comparisons of the FOXP2 gene sequences in human, chimp, and mouse.

38. Fig 19-19 A scenario for the evolution of speech in humans

39. The future of comparative genome analysis Patterns of gene expressions

40. Expression of the yeast transcriptional activator Gcn4 is controlled at the level of translation Gcn4: a transcription activator that regulate the genes that direct amino acid biosynthesis. Gcn4 itself is regulated at the translational level. Low amino acid: Gcn4 is translated High amino acid: Gcn4 is not translated.

41. uORF mRNA encoding Gcn4 contains 4 small open reading frames (uORF) upstream of the coding sequence. Once uORF1 is translated, 50% of the small subunit of ribosomes remain bound to the RNA and resume scanning for the downstream AUG start codon. However, before scanning the downstream AUG, 40s subunit must bind eIF2 and initiating tRNA fMET-tRNA.

43. Amino acid starvation: eIF2 is phosphorylated; reduce the ribosome binding efficiency. Less fMET-tRNA is available. Ribosome pass through uORF2-4 before rebinding eIF2 and fMET-tRNA for scanning.