TCGA seminar series

1
TCGA seminar series Introduction to doing
genetic history Coalescent Theory Models of
microsatellite evolution Dating methods
2
Coalescent Theory
3

• The following series of slides shows how you can
  build up a genealogical tree to relate a sample
  of 22 individuals, collected in the present day,
  at a single locus (e.g. the non-recombining Y
  chromosome).
• Because (for the Y chromosome) one son has only
  one father, but one father can have more than one
  son, coalescent events occur in the genealogy
  which inevitably result in a reduction of
  ancestors. Eventually, one ancestor remains the
  Most Recent Common Ancestor (MRCA).

4
Present
22 individuals
Time
5
Present
22 individuals 18 ancestors
Time
6
Present
22 individuals 18 ancestors 16 ancestors
Time
7
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors
Time
8
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors
Time
9
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors
Time
10
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors
Time
11
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors
Time
12
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors
Time
13
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors 7 ancestors
Time
14
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors 7 ancestors 5 ancestors
Time
15
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors 7 ancestors 5 ancestors 5
ancestors
Time
16
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors 7 ancestors 5 ancestors 5
ancestors 3 ancestors
Time
17
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors 7 ancestors 5 ancestors 5
ancestors 3 ancestors 3 ancestors
Time
18
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors 7 ancestors 5 ancestors 5
ancestors 3 ancestors 3 ancestors 3 ancestors
Time
19
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors 7 ancestors 5 ancestors 5
ancestors 3 ancestors 3 ancestors 3 ancestors 2
ancestors
Time
20
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors 7 ancestors 5 ancestors 5
ancestors 3 ancestors 3 ancestors 3 ancestors 2
ancestors 2 ancestors
Time
21
Present
22 individuals 18 ancestors 16 ancestors 14
ancestors 12 ancestors 9 ancestors 8 ancestors 8
ancestors 7 ancestors 7 ancestors 5 ancestors 5
ancestors 3 ancestors 3 ancestors 3 ancestors 2
ancestors 2 ancestors 1 ancestor
Time
22
Present
Time
23
Present
Time
Most recent common ancestor (MRCA)
24

• Mutational events can now be added to the
  genealogical tree, resulting in polymorphic
  sites. If these sites are typed in the modern
  sample, they can be used to split the sample into
  sub-clades (represented by different colours)

25
Present
TCGAGGTATTAAC TCTAGGTATTAAC
Time
mutation
Most recent common ancestor (MRCA)
26
Present
TCGAGGTATTAAC TCTAGGTATTAAC
Time
mutation
Most recent common ancestor (MRCA)
27
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC
Time
Most recent common ancestor (MRCA)
28
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC
Time
Most recent common ancestor (MRCA)
29
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC TCTAGGTG
TTAAC
Time
Most recent common ancestor (MRCA)
30
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC TCTAGGTG
TTAAC
Time
Most recent common ancestor (MRCA)
31
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC TCTAGGTG
TTAAC TCGAGGTATTAGC
Time
Most recent common ancestor (MRCA)
32
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC TCTAGGTG
TTAAC TCGAGGTATTAGC
Time
Most recent common ancestor (MRCA)
33
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC TCTAGGTG
TTAAC TCGAGGTATTAGC TCTAGGTATCAAC
Time
Most recent common ancestor (MRCA)
34
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC TCTAGGTG
TTAAC TCGAGGTATTAGC TCTAGGTATCAAC
Time
Most recent common ancestor (MRCA)
35
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC TCTAGGTG
TTAAC TCGAGGTATTAGC TCTAGGTATCAAC
Time
Most recent common ancestor (MRCA)
36

• If we now imagine that our sample of 22 was in
  fact sampled from different subpopulations, then
  allele frequencies will vary between
  subpopulations, with the degree of difference
  reflecting the time at which the population split
  took place.
• Of course, population splitting is only one model
  we can think of. Another would be a migration
  model, where lineages occasional swap from one
  subpopulation to another.
• Note that population splits do not always have to
  involve just one sub-clade of the tree in the
  figure, this is just a limitation of drawing the
  splitting in 2 dimensions only.

37
Population 2
Population 3
Population 1
Present
TCGAGGTATTAAC TCTAGGTATTAAC TCGAGGCATTAAC TCTAGGTG
TTAAC TCGAGGTATTAGC TCTAGGTATCAAC