1. How Genes and Genomes Evolve
Ch 09

2. Generating genetic variation

3. 09_01_Germ_somatic1.jpg
09_01_Germ_somatic1.jpg

4. 09_02_Germ_somatic2.jpg
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
09_03_altered.genes_Part1.jpg
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)
09_03_altered.genes_Part2.jpg
rare among eucaryotes, common among procaryotes

7. point mutations mutation frequencies:
in E. coli: 1 nt change per 109 nt pairs per cell generation
in human: 0.1 nt change per 109 nt 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. 09_04_Bac.subtilis.jpg
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
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
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 Whole-genome duplication,
(diploid genome)
Whole-genome duplication,
All chromosome amplification
Xenopus laevis
09_08_Xenopus.jpg
(duplicated genome)

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

21. 09_10_Exon.shuffling.jpg New genes generated by exon shuffling
exon shuffling can generate proteins with new combinations of protein domains.
09_10_Exon.shuffling.jpg
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. 09_11_exon.arrange.jpg
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
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
09_13_conjugation.jpg
conjugation

28. 09_14_promiscuous.jpg
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
09_16_Ancestral.gene.jpg
in the leptin gene, 5/441 nt differ between human and chimp

32. 09_17_Human_chimp.jpg
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
09_19_human_mouse1.jpg
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. 09_21_Fugu.introns.jpg Huntingtin gene
contain 67 short exons that align in 1:1 correspondence with one another
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.
09_21_Fugu.introns.jpg
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)
09_22_genetic.info.jpg

40. 09_23_tree.of.life.jpg
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 km
09_24_human.genome.jpg

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
09_25_Chromosome22.jpg

46. 09_26_noncoding.jpg
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
09_27_Computer.prog.jpg
a DNA sequence of 7500 nucleotide pairs from Candida albicans

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

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

51. 07_18_a_tropomyo.jpg alternative splicing
~60% human genes undergo alternative splicing

52. 09_30_alt.splice.RNA.jpg
alternative splicing of Drosophila DSCAM transcripts
final mRNA transcript contains 23 exons
09_30_alt.splice.RNA.jpg
1A+1B+1C+1D+19 invariant exsons
alternative splicing of RNA transcripts can produce many distinct proteins

53. 06_28_Homol.recomb1.jpg
06_28_Homol.recomb1.jpg

54. 06_29_Homol.recomb2.jpg
06_29_Homol.recomb2.jpg