DNA Sequence Analysis

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DNA Sequence Analysis
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Mitochondrial
Nuclear
A
A A
Generation 1
A
A
A
Generation 2
A A
mutation
A
A
Generation 3
A A
B
A
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Northern Alaska
AACCAACCTCCCTAAGACTCAAGGAAGAAGCTATAGCCCCACTATCAACA
CCCAAAGCTGAAGTTCTATTTAAACTATTCCCTGGCGCATATTAATATAG
TTCCACAAAATTCAAGAACCTTATCAGTATTAAATTCTTAAAAATCTTTA
ACAATTTAATACAGTTTTGTACTCAACAGCCATATTAATATTTCATATAC
CATTAATTACACTAAGTACATAATGATTTATATGCATCAGTACTCCATAC
GGGTATAGTACATAACATTAATGTATCAAGACATATTATGTATAATAGTA
CATTACACTATTTACCCCATGCTTATAAGCAAGTACATGACATTATTAAT
AGTACATAGTACATATTATTATTGATCGTACATAGCACATTATGTCAAAT
CCATTCTTGTCAACATGCGTATCCCGTCCATTAGATCACGAGCTTAATCA
CCATGCCGCGTGAAACCAACAACCCGCTTGGCAAGGATCCCTCTTCTCGC
TCCGGGCCCATGCACTGTGGGGGTAGCTATTTCATGAACTTTATCAGACA
TCTG
Statewide Alaska
AACCAACCTCCCTAAGACTCAAGGAAGAAGCTATAGCCCCACTATCAACA
CCCAAAGCTGAAGTTCTATTTAAACTA TTCCCTGGCGCATATTAATATA
GTTCCACAAAATTCAAGAACCTTATCAGTATTAAATTCTTAAAAATCTTT
AACAA TTTAATACAGTTTTGTACTCAACAGCCATATTAATATTTCATAT
ACCATTAATTACACTAAGTACATAATGATTTAT
ATGCATCAGTACTCCATACGGGTATAGTACATAACATTAATGTATCAAGA
CATATTATGTATAATAGTACATTACAC TATTTACCCCATGCTTATAAGC
AAGTACATGACATTATTAATAGTACATAGTACATATTATTATTGATCGTA
CATAG CACATTATGTCAAATCCATTCTTGCCAACATGCGTATCCCGTCC
ATTAGATCACGAGCTTAATCACCATGCCGCGTG
AAACCAACAACCCGCTTGGCAAGGATCCCTCTTCTCGCTCCGGGCCCATG
CACTGTGGGGGTAGCTATTTCATGAAC TTTATCAGACATCTG
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Distance measures

• Number of differences
• d different sites
• p-distance
• Proportion of sites different
• d nd /L, where L number of sites
• Neither of these correct for multiple hits
• Assume equal rates of substitution among all
  pairs of nucleotides
• Assume equal rates among sites

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Jukes-Cantor

• d -¾ln(1-4/3p)
• Assumes
• rates of substitutions between all possible
  nucleotides are equal
• Equal nucleotide frequencies
• Equal rates among sites
• Corrects for multiple hits

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Tajimi-Nei

• Assumes
• rates of substitutions between all possible
  nucleotides are equal
• Equal rates among sites
• Allows for unequal nucleotide frequencies
• Corrects for multiple hits

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Kimura 2-parameter (K2P)

• Assumes
• Equal nucleotide frequencies
• Equal rates among sites
• Corrects for multiple hits
• Allows different rates between transitions and
  transversions

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Tamura 3-parameter

• Assumes
• Equal rates among sites
• Corrects for multiple hits
• Allows different rates between transitions and
  transversions
• Corrects for GC-content bias

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Tamura-Nei(similar to HKY)

• Assumes
• Equal rates among sites
• Corrects for multiple hits
• Accounts for different nucleotide frequencies
• Accounts for difference in rates between
  transitions and transversions
• Accounts for different rates of substitutions in
  transitions of purines (a1) versus pyrimidines
  (a2)

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Which to choose?

• A range of complexity
• All models are accurate at low genetic distances
• More complex models are more accurate when
  distances are large
• Why not use all the timewhy keep talking about p
  distances or K2P?
• Complex models have higher variance

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When rates differ among sites

• Variation in rates can be modeled
• Gamma distribution (G)
• Gamma parameter (shape parameter) a
• Can be applied to any distance measure

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Genetic rescue of Norfolk Island
boobok Cytochrome b sequence differences NI
boobookNZ boobook 2 NI boobookTas boobook
8 NZ boobookTas boobook 8 NIpowerful owl
21 NIrufous owl 23 Powerful owlrufous owl 13
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Phylogeography
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For next time

• Read 2 beluga papers posted on website