How Genes and Genomes Evolve

1. How Genes and Genomes Evolve Ch 09

2. Generating genetic variation

3. 09_01_Germ_somatic1.jpg

4. 09_02_Germ_somatic2.jpg

5. 09_03_altered.genes.jpg nt change, delete, duplication DNA replication, repair creating a set of closely related genes within a single cell chromosome breakage, repair breaking and rejoining within intron sequences of genes does not have to be precise to result in a functional gene

6. Figure 9-3 Part 2 (intercellular gene transfer) rare among eucaryotes, common among procaryotes

7. point mutations • mutation frequencies: • in E. coli: 1 nt change per 109nt pairs per cell generation • in human: 0.1 nt change per 109nt pairs each time the DNA is copied

8. point mutations • provide a way of fine tuning the function of a gene by making small adjustments to its sequence • can also eliminate the activity of genes • very often, however, point mutations do neither of these things; at many sites in the genome, a point mutation has absolutely no effect on the appearance or viability of the organism.

9. silent, selectively neutral mutations • the mutations leads to no alteration in the A.A. sequence of any protein, or in the function of any regulatory piece of DNA. • such mutations accumulate steadily in the genome of a species over evolutionary time, can be used like the ticks of an evolutionary clock to estimate how many generations separate two individuals, or two closely related species, from their last common ancestor

10. DNA duplications give rise to families of related genes within a single cell • gene duplication and divergence: • generating new genes • giving rise to families of related genes within a single cell • ex: • Bacillus subtilis genome- • eucaryotic genomes- opsins, collagens, globins, … • different opsins- detecting light of different wavelengths, are expressed in different retinal cell • different collagens- are expressed in the various types of connective tissue • globins- increase carrying efficiency of oxygen

11. Bacillus subtilis genome- contains many families of evolutionarily related genes 09_04_Bac.subtilis.jpg Largest gene family: the “ABC transporters” contains 77 genes ABC transporters: a class of proteins that transport various materials across the cell membrane gene duplications and divergence give rise to families of related genes within a single cell

12. 09_05_Gene.duplicate.jpg (remnants of transposons) (homologous recombination)

13. 09_06_globin.1.jpg cooperative allosteric change

14. The globin gene family • Oxygen-binding proteins • The most primitive oxygen-carrying molecule in animal: a globin polypeptide of ~150 aa (marine worms, insects, primitive fish) • The hemoglobin molecule: • in higher vertebrates (higher fish): composed of two kind of globin (α- and β-globin chain) • in modern higher vertebrates: a complex of two α- and two β-globin chain (α2β2) • in mammals…….

15. mammals primates β (adults) δ:(α2δ2)- in adults β ε: (α2ε2)- in early development stage β like (fetus) (higher affinity for O2) γG γ: (α2γ2)- in fetus in fetus γA • each of these duplicated genes has been modified by point mutations • affect the properties of the final hemoglobin molecule • change in regulatory regions (gene expression at different times and with different levels when development) • there are several duplicate globin DNA sequences in the α- and β-globin gene cluster

16. 09_07_globin.2.jpg

17. each of these duplicated genes has been modified by point mutations • affect the properties of the final hemoglobin molecule • change in regulatory regions (gene expression at different times and with different levels when development) • there are several duplicate globin DNA sequences in the α- and β-globin gene cluster that are not functional genes, but pseudogenes

18. Gene duplication and divergence provide a critical source of genetic novelty for evolving organisms • provide an organism with a cornucopia of spare gene copies, which are free to mutate to serve divergent purposes • almost every gene in the genome of a vertebrate exists in multiple versions

19. 09_08_Xenopus.jpg Xenopus tropicalis (diploid genome) Whole-genome duplication, All chromosome amplification Xenopus laevis (duplicated genome)

20. New genes can be generated by repeating the same exon (internal duplications) 09_09_exon.jpg exon shuffling long introns short exons many genes in eucaryotes are composed of a series of repeating protein domains, such as albumins, immunoglobulins, collagens, ……

21. New genes generated by exon shuffling 09_10_Exon.shuffling.jpg exon shuffling can generate proteins with new combinations of protein domains. domain:small discrete region of a structure A protein domain is a compact and stable folded region of polypeptide. (A membrane domain is a region of bilayer with a characteritistic lipid and protein composition.)

22. It has been proposed that all the proteins encoded by the human genome (~30000) arose from the duplication and shuffling of a few thousand distinct exons, each encoding a protein domain ~30-50 aa.

23. The evolution of genomes has been accelerated by the movement of transposable elements 09_11_exon.arrange.jpg is a frequent cause of spontaneous mutation p. 301

24. The activity of transposons can also change the way that existing genes are expressed. • Ex: an insertion of a tansposon in the regulatory region of a gene • Transposons are a significant source of developmental changes, and they are thought to have been particularly important in the evolution of the body plans of multicellular plants and animals.

25. 09_12_Mutation.jpg Mutation due to a transposable element can induce dramatic alterations in the body plan of an organism.

26. Horizontal gene transfer • Genes are exchanged between organisms. • This mechanism is rare among eucaryotes, but common among bacteria. • Such genetic exchanges are currently responsible for the rise of new and potentially dangerous strains of drug-resistant bacteria.

27. 09_13_conjugation.jpg conjugation

28. 09_14_promiscuous.jpg

29. Reconstructing life’s family tree

30. 09_15_Phylogen.trees.jpg phylogenetic tree: (p. 306) *homologous genes: genes that are similar in their nucleotide sequence p304

31. 09_16_Ancestral.gene.jpg in the leptin gene, 5/441 nt differ between human and chimp

32. 09_17_Human_chimp.jpg

33. Alu retrotransposon has had only minor effects on the overall structure of human and chimp genomes. • Most of the Alu sequences in our genome underwent duplication and transposition before humans and chimpanzees diverged.

34. 06_35_L1 and Alu-like.jpg Alu L1 L1 B1 (~ human Alu) The positions of transposons in the human and the mouse genomes provide additional evidence of the long divergence time separating the two species.

35. Functionally important sequences show up as islands of DNA sequence conservation • conserved synteny-(p. 307) • regions where corresponding genes that began as neighbors have remained neighbors, strung together in the same sequence in both species

36. 09_19_human_mouse1.jpg Coding sequence of exson is much more conserved than the intron sequence Purifying selection: the elimination of individuals carrying mutations that interfere with important functions. exons, rRNA gene, regulatory proteins binding sites p. 308

37. 09_20_puffer.fish.jpg Fugu rubripes • genome size 400 million bp: ~1/4 of zebrafish; ~1/8 of human • gene no., structure, position,…. almost the same with human… • with the shortest intrones in all species

38. Huntingtin gene contain 67 short exons that align in 1:1 correspondence with one another 09_21_Fugu.introns.jpg • The human gene is 7.5 times larger than the Fugu gene, due entirely to the presence of larger intrones in the human sequence. • The larger size of human intrones is a result in part of the presence of transposable elements. • The positions of Fugu introns are conserved relative to their positions in mammalian genomes. • The “junk DNA” is dispensable.

39. 09_22_genetic.info.jpg Some genetic information has been conserved since the beginnings of life. (a part of the ss rRNA gene sequence)

40. Sequence conservation allows us to trace even the most distant evolutionary relationships • The living world has three major divisions (domains) 09_23_tree.of.life.jpg (by ss rRNA gene sequences)

41. Examining the human genome

42. 09_24_human.genome.jpg If each nt pair is drawn to span 1 mm, then the human genome would extended 3200 km

43. Human genome • Entire human genome- • 3.2  109 nucleotide pairs • 22 autosomes and 2 sex chromosomes • Individual humans differ from one another by an average of 1 nucleotide in 1000

44. The human chromosome 22, one of the smallest human chromosomes The first human chromosome to have its nucleotide sequence determined

45. 09_25_Chromosome22.jpg

46. 09_26_noncoding.jpg regulatory DNA equences: are typically spread out over tens of thousands of nucleotide pairs, most of which is “spacer” DNA

47. Genetic variation within the human genome contributes to our individuality • SNPs- single-nucleotide polymorphisms(p.313) • single base changes in the same region of the genome from two different humans • when the same region of the genome from two different humans is compared, the nucleotide sequences typically differ by about 0.1% • more than 3 million SNPs had been located • more than 90% of all human genes contain at least one SNP • CA repeats-(p. 316)

48. 09_27_Computer.prog.jpg Counting genes finding genes by computer programs a DNA sequence of 7500 nucleotide pairs from Candida albicans

49. 09_28_human_mouse2.jpg centromere mouse human The human and mouse genomes contain many regions where the order of genes has been preserved

50. Regulatory genes and proteins define an organism’s developmental program 09_29_developmental.jpg