Patterns of Substitution and Replacement

1. Patterns of Substitution and Replacement

6. Pattern of Substitution* in Pseudogenes *Based on a sample of 105 mammalian retropseudogenes.

7. The sum of the relative frequencies of transitions is ~68% If all mutations occur with equal frequencies the expectation is 33%

8. In comparison to the 50% expectation, 59.2% of all substitutions are from G and C, and 56.4% of all substitutions are to A and T. In the absence of selection, DNA will tend to become AT-rich

9. (CG dinucleotides excluded)

13. Pattern of Substitution* in mtDNA *Based on 95 sequences from human and chimpanzee.

14. The sum of the relative frequencies of transitions is ~94% If all mutations occur with equal frequencies the expectation is 33% *Based on 95 sequences from human and chimpanzee.

15. Mutations: Strand (Leading and Lagging) Effects

16. Possible inequalities between strands A change from G to A actually means that a G:C pair is replaced by an A:T pair. This can occur as a result of either a G mutating to A in the one strand or a C to T mutation in the complementary strand. Similarly, a change from C to T can occur as a result of either a C mutating to T in one strand or a G mutating to A in the other.

17. Detection of Strand Inequalities in Mutation Rates • If G  A on leading strand, then C  T on lagging strand • If G  A on lagging strand,then C  T on leading strand • If G  A on leading = G  A on lagging,then G  A = C  T

19. If there are no differences in the mutation pattern between the two strands, then

20. Is G  A = C  T? The transitional rate between pyrimidines (C, T) is much higher than that between purines (G, A), suggesting different patterns and rates of mutation between the two strands.

21. Pattern of amino-acid replacement

22. Physicochemical distances = measures for quantifying the dissimilarity between two amino acids.

25. Grantham’s physicochemical distances between pairs of amino acids

26. The most similar amino acid pairs are leucine and isoleucine (Grantham's distance = 5) and leucine and methionine (Grantham's distance = 15).

27. 215 205 202 The most dissimilar amino acid pairs

28. A replacement of an amino acid by a similar one (e.g., leucine to isoleucine) is called a conservative replacement. A replacement of an amino acid by a dissimilar one (e.g., glycine to tryptophan) is called a radical replacement.

29. Empirical findings: During evolution, amino acidsare mostly replaced by similar ones.

30. A lot A little Similar amino acids Dissimilar amino acids

31. Similar Dissimilar

32. Kimura 1985

33. Exchanges between similar structures occur frequently. Exchanges between dissimilar structures occur rarely. Nothing happens, but if it does, it doesn’t matter.

34. Amino-acid exchangeability Numbers in parentheses denote codon family for amino acids encoded by two codon families 60-90% of the amino-acid replacements involve the nearest or second nearest neighbors in the ring Argyle’s exchangeability ring

35. What protein properties are conserved in evolution? Protein specific constraints: The evolution of each protein-coding gene is constrained by the specific functional requirements of the protein it produces. General constraints: Are there general properties that are constrained during evolution in all proteins?

36. bulkiness (volume) high low degree of conservation

37. hydrophobicity high low degree of conservation

38. polarity high low degree of conservation

39. optical rotation high low degree of conservation

40. surprise! charge optical rotation high low degree of conservation

47. Amino-acid composition may be an important factor in determining rates of nucleotide substitution.

48. Most conserved amino acids: Glycineis irreplaceable because of its small size. Lysine is irreplaceable because of its involvement in amidine bonds that crosslink polypeptide chains Cysteineis irreplaceable because of its involvement in cystine bonds that crosslink polypeptide chains Proline is irreplaceable because of its contribution to the contortion of proteins.

49. Does the frequency of amino acids in proteins reflect “functional need” or “availability”?

50. The frequencies of nucleotides in vertebrate mRNA are 22.0% uracil, 30.3% adenine, 21.7% cytosine, and 26.1% guanine.