Human Evolution Timelines

1
Human Evolution Timelines
Research History
Evolution History
Source Jobling, Hurles Tyler-Smith (2004)
Human Evolutionary Genetics.
2
Human Evolution
The Data Genetic Allele Frequencies, SNPs,
Haplotypes Non-genetic Language, culture,
pets,pathogens, culture,.. The Dynamics
Mutation, selection, recombination, The
Genealogical Structure Phylogeny, Ancestral
Recombination Graph, Pedigree
Relationship to the great Apes, Ancestral
Population of Human/Chimp Ancestor, Out of Africa
Ancestral Population Structure, Selection,
Migrations Age of Alleles. Genealogies
Iceland Models of Pedigrees Languages
Pathogens
3
Populations Basic Genealogical Structures
Pedigree Trace the ancestry of individuals
Grand parents
Phylogeny Trace the ancestry of sequence points.
Parents
ARG Trace the ancestry of sequences
Now
Other Genealogical Structures are possible
network, language merging, population splitting
4
Recombination
1 meiosis

• Total Haploid length males 25.9 M - females
  44.6 M.
• Gene conversions 1-2 orders higher. Length
  300-2000 pb.

Lander et al.(2001) Initial sequencing and
analysis of the human genome Nature 409.860-912.
Kong,E. et al.(2002) A high resolution
recombination map of the human genome Nature
Genetics
5
Mutations and Mutation Rates
1 mitosis or generation
Average Number of Mitoses Per Male generation
(1535 .. 20150) Per Female generation 24

• Single nucleotide substitutions 10-7
• Microsatellites (100.000) 10-2
• Small insertion deletions 10-8

Selection Positive Negative
Crow,JF (2000) The Origins, Patterns and
Implications of Human Spontaneous Mutation
Nature Review Genetics 1.1.40-47 Strachan and
Read (2004) chapter 11 Jobling, Hurles and
Tyler-Smith (2004) chapter 2
6
Coalescent Issues

1. The number of genetic ancestors
2. When gene-trees differ from species trees
3. Out of Africa
4. Ages of Alleles
5. Allele Gradients
6. Number of Genetic Ancestors
7. Selective Sweeps

7
Human History Levels Physical, Cultural
Genealogical
The physical population size, N(t), and the
efficient population size, Ne(t) are separate
concepts. i. N(t)can mainly be studied by
historical/archeological means, ii. Ne(t)
can be studied genealogically, for instance by
tracing the ancestries of DNA sequences.
Main departures from simplest Population
Genetical Models A. Long epochs of exponential
growth at increasing rates B. Bottlenecks small
populations. C. Migrations Geographical
subdivisions
8
Our relationship to the great Apes. From Nei,2003
13 Myr
7 Myr
5.5 Myr
1 Myr
Chimp
Pygmee Chimp
Orangutan
Humans
Gorilla
9
Ancestral Population of Human and Chimp
7 Myr
G
H
5 Myr
C
Human
Now
Chimp
Gorilla
Example Chen Li (2001) 53 triads 31 (H,C),
10 (H,G) 11 (C,G)
10
Out-of-Africa and different degrees of
replacements
Total replacement
No replacement
Partial replacement
1-1.2 Myr
1-1.2 Myr
1-1.2 Myr
80-130 Kyr
80-130 Kyr
80-130 Kyr
Africa
Europe
Asia
Africa
Asia
Europe
Asia
Africa
Europe
Example Takahata (2001) found data could be
explained by total replacement.
11
Allele Frequencies and Principal
Components Cavalli-Sforza,2001

• Allele frequencies for different localities are
  subjected to a smoothing procedure.
• Principle Components are found and projected on
  geographical maps.
• Strongly criticized (Sokal et al.) even no
  geographical structure will look like
  geographical structure, no timing of
  gradients,...

1. Agriculture 6-10 Kyr
2. Greek Colonisation 3 Kyr
3. Retraction of the Basques
4. Uralic People
5. Horse domestication

12
Time slices
All positions have found a common ancestors on
one sequence
All positions have found a common ancestors
Time
1 2
1 2
1 2
1 2
1 2
N
1
Population
13
Number of genetic ancestors to the Human Genome
Sr number of Segments E(Sr) 1 r
time
C
C
C
R
R
R
sequence
Simulations
Statements about number of ancestors are much
harder to make. Wiuf conjectured r/ln(r)
14
Applications to Human Genome (Wiuf and Hein,97)
Parameters used 4Ne 20.000 Chromos. 1 263 Mb.
263 cM Chromosome 1 Segments 52.000
Ancestors 6.800 All chromosomes Ancestors
86.000 Physical Population. 1.3-5.0 Mill.
A randomly picked ancestor (ancestral material
comes in batteries!)
15
Many sampled alleles relative to Ne Wakeley03,
Pitman, Schweinberg
1. Simultaneous Events 2. Multifurcations. 3.
Underestimation of Coalescent Rates
16
Cystic Fibrosis (Wiuf 2000) ?F508 possibly
maintained by heterosis (1.023)- higher
resistance to Salmonella infections. Data 1.
Frequency of ?F508-allele - .022. 2. Inter
variability in 1.705 individuals 46 variable
positions. 3. Model of human demography.
Model parameters mutation rate, heterosis
advantage and an exponential growth model of
human population expansion.
Estimated age of ?F508 is estimated to be

17
Pedigree Issues
Chinese http//demography.anu.edu.au/People/Staff/
zhongwei.html
Burkes British Peerage http//www.burkes-peerage.
net/sites/wars/sitepages/home.asp
Mormons http//genealogy-mormons.com/
Quebec French Heyer and Tremblay, 1998 PNAS
Icelandic http//www.decode.com Helgason, A. et
al. (2003 June) A population-wide coalescent
analysis of Icelandic matrilineal and
patrilineal genealogies Evidence for a faster
evolutionary rate of mtDNA lineages than
Y-chromosomes American Journal Human Genetics.

• i. Icelandic Pedigree
• Theoretical Models

18
Icelandic Genealogies Helgason, 2003
Males only
Females only
Of (June 2002) 276,00 Icelanders 131,060 born
after 1972 was traced back.
19
Icelandic Genealogies Helgason, 2003
Ancestors to 1972 cohort
Backtracable
20
Icelandic Genealogies Helgason, 2003
Variation in annual offspring number greater for
females in males, due to shorter generation time.

Positive correlation in fertility between
parent-offspring.
21
Finding Ancestral Individuals. Joe Chang 1999
Dec. Adv. Appl. Prob.
11
10
9
8
7
Finding (Great)k Grand Parents.
6
5
4
3
2
1
NOW
0
Let T be the time, when somebody was everybodys
ancestor. Changs result lim
T/log2(N) 1 prob. 1
22
Combining Ancestral Individuals and the
Coalescent Wiuf Hein, 2000.
Finding Common Ancestors.
NOW
Unify the two processes Sample more
individuals Let each have p parents. ( p
possibly stochastic gt 1). Result A
discontinuity at 1. For pgt1
change log2?logp Comment Genetic Ancestors is a
vanishing set within Genealogical Ancestors.
23
Derrida
G 1
G
Recursion
a individual, g ancestor in tree, w - weight
probability that uni. random path leads to g.
Initialization
24
Kammerle 89 Pair Moran Model
A pair of children are born they choose parents
randomly. A pair is erased and the children pair
take their place.
A. The stationary distribution of number of
ancestors to present population is hypergeometric
y
0
25
Non-Contributing Ancestors Kevin Donnelly, 1983
TPB
No Recombination
Recombination
Generation
Ancestors
2k
k
46 packets
lt k72 46 packets
21
1
1
y
1
22
22
x
lt72 46 packets
46 packets
x
x
.
.
y
1
y
1
22
22
0
1
46 packets
46 packets
26
Non-Contributing Ancestors Yun song- pers.comm.,
2003 Kevin Donnelly, 1983
The probability of 1. Any non-contributing
ancestor 2.That a randomly chosen ancestors
is non-contributing
1
2
4
8
16
32
From Yun Song
Back in Time
64
128
256
512
27
Pedigree Inference
Prior on Pedigrees
Three Processes

1. Choosing Parents
2. Recombination
3. The Mutational Process

Probability of data given pedigree
Posterior on Pedigrees
Elston-Stewart (1971) -Temporal Peeling
Algorithm Lander-Green (1987) - Genotype Scanning
Algorithm
28
Inheritable phenomena
Genetic Material Sequences Allele
Frequencies Language Culture Pathogens
Pests Pets Morphological Characters
29
Pathogen phylogenies Falush 2003
Helicobacter pylori is transmitted from mother to
child. Falush et al. sequenced 8 genes from 370
strains from 27 populations 3850 nucletides
each. 5 ancestral populationsEast Asia, Euro1,
Euro2, Afr1 Afr2 Structure assign each
polymorphism to an ancestral population. American
indians are grouped as asian showing that
H.pylori infection is ancient. Diversity of
H.pylori 50 times larger than humans. Much
recombination i.e. positions can be treated as
independent

1. Maori is east asian.
2. Inuit is Euro1 Euro2
3. South African Afr2
4. English

30
Cavalli- Sforza Language Trees Cavalli-Sforza
(1997) Genes Peoples and Languages PNAS 94.7719-24
Principle of Comparison. Loss of cognates
(homologous words) Syntax Comparison.
Sound use. Reconstruction (dependent on
interpretation) stretches back 2-6.000 years
dependent on criteria.
31
Historical Linguistics
William Jones 1776 observes similarities between
Sanskrit, Greek Latin Swadesh (1952) makes on
of the first glottochronological studies Kruskal,
Dyer Black (1971) large successful
investigation.
Principles Distance - Swadesh rule. 20
lost per millenium. Parsimony
Compatibility Likelihood
Criticisms Word Loss is not clocklike
Languages and merge and borrow giving non-tree
like structure Not much research goes into
this area.
32
Khoisan
Global Phylogeny Cavalli-Sforza,2001 Ruhlen, 1994
African
Niger-Kordofanian
Congo-Saharan
Nilo-Saharan
Afro-Asiatic
Kartvelian
Dravidian
Indo-European
Uralic
Eurasiatic 20-10 Kyr
Altaic
Eurasion/American 40-20 Kyr
Eskimo-Aleut
Chukchi-Kamchatkan
Home sapiens sapiens 100-70 Kyr
Amerind
Na-Dene
Eurasian 60-40 Kyr
Dene-Caucasian 40-20 Kyr
Sino-Tibetan
Caucasian/Basque/Burushaski
Austronesian
Asian 70-50 Kyr
Daic
Austro-Tai
Miao-Yao
Austric
Austro-Asiatic
Dene-Caucasian 40-20 Kyr
Indo-Pacific
Pacific
Australian
33
Afghan Baluchi Persian Osetic Bengali Hindi Punjab
i Marathi Nepali Kashmiri Singhalese Breton Welch
Irish Bulgarian Macedonian Serbo
Croatian Belorussian Ukranian Polish Chech Russian
Slovenian Latvian Lithuanian French Walloon Ital
ian Ladin Portugese Spanish Sardinian Rumanian Dan
ish Swedish Riksmaal Faraoese Icelandic Dutch Germ
an Frisian English Greek Armenian Albanian
Indo-European Language Trees Dyen, Kruskal
Black, 1992 Piazza, Cavalli-Sforza, 2001
Celtic
Slavic
Romance
Germanic
6000
7000
9000
8000
5000
4000
3000
2000
1000
34
Germanic Language Trees From Embleton, 1986
Swedish
1540
Danish
1803
Norwegian
Faraoese
1051
Icelandic
1842
English
194
Tok Pisin
1051
Frisian
246
Flanders
1239
Africaans
1668
1423
Dutch
1025
1051
1234
Yiddish
1476
Hamburg Lower Saxony
Pennsylvanian German
1558
German
TrS
35
The Coalescent Human Evolution (11.6.04)
Human History Methodological Problems
Reconstucting haplotypes, defining haplotype
blocks HapMap. Relationship to the great
Apes, Ancestral Population of Human/Chimp
Ancestor, Out of Africa, The Neanderthal.
Human Population Growth, Ancestral Population
Structure, Selection, Migrations Age of
Alleles. SNPs? Haplotypes, Recombination
Hotspots Haplotype Blocks. Individual
Stories Mitochondria, Y, autosomal chromosomes
alleles. Emperical Genealogies Iceland Other
Genealogical Issues Genealogical Ancestors,
Genetic and Non-Contributing Ancestors Heritable
Characters Languages Associated Animals,
Plants Pathogens Surnames Morphological
Characters The Role of Coalescent Theory