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1. Introduction
2. Deoxyribonucleic acid (DNA) structure
3. The genetic code
4. Given 4 nucleotides and 20 amino acids
5. Codon chart
6. Nucleotide substitutions in coding regions
7. Synonymous and nonsynonymous sites
8. DNA code redundancy and natural selection
9. Natural selection - Darwin and Wallace 1859
10. Natural selection: the basic idea
11. Two kinds of natural selection
12. Purifying selection
13. Positive (Darwinian) selection
14. Two forms of positive selection
15. A relationship described by Motoo Kimura
16. The total mutation rate variation
17. Synonymous vs. nonsynonymous sites
18. Nucleotide substitutions per site
19. Comparing dS and dN: dS greater than dN
20. Computing dS and dN
21. Comparison of orthologous loci: human vs. mouse
22. Ratio mean dS: mean dN = 6.5:1
23. Comparing dS and dN: dN greater than dS
24. Example of positive selection at the DNA level
25. The major histocompatibility complex (MHC)
26. Two main subfamilies of MHC genes
27. Class I MHC
28. HLA-A, -B, and -C are highly polymorphic
29. Two MHC mysteries
30. Zinkernagel and Doherty (1974)
31. Schematic view of MHC class I function
32. MHC class I structure
33. Peptide-binding region (PBR)
34. Doherty and Zinkernagel's (1975) hypothesis
35. Predictions about nucleotide substitutions
36. dN and dS in PBR
37. dN and dS in non-PBR
38. Nucleotide substitution at MHC loci
39. Class I MHC apply selective pressure on viruses
40. CTL escape mutation
41. Experiments with SIV in rhesus monkeys
42. CTL epitope in the tat protein of SIV
43. Genome map of SIV
44. dS and dN: tat and vpr genes
45. Amino acid replacements in tat epitope
46. Convergent evolution
47. Rhesus monkey/SIV model system
48. Importance of purifying selection
49. Complex disease
50. Single nucleotide polymorphisms (SNPs)
51. Frequency data for 1442 SNPs
52. Silent versus nonsynonymous SNPs
53. Gene diversity for different SNPs categories
54. Evidence for purifying selection on common SNPs
55. Nonsynonymous SNPs cause less radical changes
56. Comparison with mouse model (1)
57. Comparison with mouse model (2)
58. Candidate SNPs for complex diseases association
59. Slightly deleterious SNPs in the human genome
60. Effect of bottleneck on allele frequency
61. Natural selection - brief history of an idea
62. Natural selection at the DNA level
63. Two kinds of natural selection: conclusions

Topics Covered

• Inferring selection from patterns of nucleotide substitution
• The Major Histocompatibility Complex as an example of positive selection
• Immunodeficiency virus escapes from immune recognition
• Purifying selection on Single Nucleotide Polymorphisms

Links

Series:

• Human Population Genetics I

Categories:

• Genetics & Epigenetics
• Methods

Talk Citation

Publication History

• Published on October 1, 2007
• Archived on February 25, 2021

Financial Disclosures

• Prof. Austin Hughes has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.