Lecture 7 Mutation and genetic variation

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1 Lecture 7 Mutation and genetic variation

2 Thymidine dimer

4 Natural selection at a single locus 2. Purifying selection a form of selection acting to eliminate harmful (deleterious) alleles from natural populations. - example: human recessive diseases like Tay- Sachs or porphyria.

5 Genetic code

6 Phylogenetic reconstructions 3. Maximum Likelihood α A G α A G α α α α β β β β C T α Jukes-Cantor Model C T α Kimura - 2 parameter Model

7 Mutation hotspots Cytochrome b

9 Molecular clock Emile Zuckerkandl and Linus Pauling, 1965

11 Synonymous substitutions v.s. Non-synonymous substitutions Ka/Ks is an indicator of selection

12 General classes of mutations Point mutations Copy-number mutations Chromosomal mutations Genome mutations

13 Point mutations There are four categories of point mutations: 1. transitions (e.g., A G, C T) 2. transversions (e.g., T A, C G) α A G β β β β C T α

14 Point mutations There are four categories of point mutations: 1. transitions (e.g., A G, C T) 2. transversions (e.g., T A, C G) 3. insertions (e.g., TTTGAC TTTCCGAC) 4. deletions (e.g., TTTGAC TTTC) in coding regions, point mutations can involve silent (synonymous) or replacement (nonsynonymous) changes. in coding regions, insertions/deletions can also cause frameshift mutations.

15 Indels are insertions and deletions STOP making sense: effective frameshifts

16 Loss of function mutations in the cystic fibrosis gene

17 Copy-number mutations

18 Copy-number mutations these mutations change the numbers of genetic elements.

19 Copy-number mutations these mutations change the numbers of genetic elements. gene duplication events create new copies of genes.

20 Copy-number mutations these mutations change the numbers of genetic elements. gene duplication events create new copies of genes. one important mechanism generating duplications is unequal crossing over.

21 Unequal crossing-over can generate gene duplications

22 Unequal crossing-over can generate gene duplications

23 Unequal crossing-over can generate gene duplications lethal? neutral?

24 Copy-number mutations these mutations change the numbers of genetic elements. gene duplication events create new copies of genes. one mechanism believed responsible is unequal crossing over. over time, this process may lead to the development of multi-gene families.

25 α and β-globin gene families Chromosome 11 Chromosome 16

26 Timing of expression of globin genes

27 Retrogenes may also be created retrogenes have identical exon structures to their progenitors but lack introns!

28 Retrogenes may also be created retrogenes have identical exon structures to their progenitors but lack introns! Example: jingwei in Drosophila yakuba

29 Retrogenes may also be created retrogenes have identical exon structures to their progenitors but lack introns! Example: jingwei in Drosophila yakuba Alcohol dehydrogenase (Adh) Chromosome 2 Chromosome 3

30 Retrogenes may also be created retrogenes have identical exon structures to their progenitors but lack introns! Example: jingwei in Drosophila yakuba Alcohol dehydrogenase (Adh) mrna Chromosome 2 Chromosome 3

31 Retrogenes may also be created retrogenes have identical exon structures to their progenitors but lack introns! Example: jingwei in Drosophila yakuba Alcohol dehydrogenase (Adh) mrna cdna Chromosome 2 Chromosome 3

32 Retrogenes may also be created retrogenes have identical exon structures to their progenitors but lack introns! Example: jingwei in Drosophila yakuba Alcohol dehydrogenase (Adh) mrna cdna jingwei Chromosome 2 Chromosome 3

33 Whole-genome data yields data on gene families

34 Copy-number mutations transposable elements (TEs) are common.

35 Copy-number mutations transposable elements (TEs) are common. three major classes of TEs are recognized:

36 Copy-number mutations transposable elements (TEs) are common. three major classes of TEs are recognized: 1. insertion sequences ( bp)

37 Copy-number mutations transposable elements (TEs) are common. three major classes of TEs are recognized: 1. insertion sequences ( bp) 2. transposons ( bp)

38 Copy-number mutations transposable elements (TEs) are common. three major classes of TEs are recognized: 1. insertion sequences ( bp) 2. transposons ( bp) 3. retroelements

39 Chromosomal inversions lock blocks of genes together

40 Changes in chromosome number are common

41 Changes in chromosome number are common Robertsonian fusions and fissions are common and can have major effects on speciation

42 Changes in chromosome number are common Robertsonian fusions and fissions are common and can have major effects on speciation in mammals, chromosome numbers range from N = 3 to N = 42.

43 Changes in chromosome number are common Robertsonian fusions and fissions are common and can have major effects on speciation in mammals, chromosome numbers range from N = 3 to N = 42. in insects, the range is from N = 1(some ants) to N = 220 (a butterfly)

44 Changes in chromosome number are common Robertsonian fusions and fissions are common and can have major effects on speciation in mammals, chromosome numbers range from N = 3 to N = 42. in insects, the range is from N = 1(some ants) to N = 220 (a butterfly) karyotypes can evolve rapidly!

45 Muntiacus reevesi Muntiacus muntjac

46 Muntiacus reevesi; N = 23 Muntiacus muntjac; N = 4

47 Genome mutations

48 Genome mutations polyploidization events cause the entire genome to be duplicated.

49 Genome mutations polyploidization events cause the entire genome to be duplicated. polyploidy has played a major role in the evolution of plants.

50 Genome mutations polyploidization events cause the entire genome to be duplicated. polyploidy has played a major role in the evolution of plants. ancient polyploidization events have also occurred in most animal lineages.

51 Generation of a tetraploid

52 Where do new genes come from?

53 Where do new genes come from? An example: the antifreeze glycoprotein (AFGP) gene in the Antarctic fish, Dissostichus mawsoni Convergent evolution of an AFGP gene in the arctic cod, Boreogadus saida

- mutations can occur at different levels from single nucleotide positions in DNA to entire genomes.

- mutations can occur at different levels from single nucleotide positions in DNA to entire genomes. February 8, 2005 Bio 107/207 Winter 2005 Lecture 11 Mutation and transposable elements - the term mutation has an interesting history. - as far back as the 17th century, it was used to describe any drastic