Human Evolution Timelines

Source: Jobling, Hurles & Tyler-Smith (2004) Human Evolutionary Genetics.

Research History Evolution History

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

Human Evolution

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

Populations & Basic Genealogical Structures

Now

Parents

Grand parents

Pedigree: Trace the ancestry of individuals

Phylogeny: Trace the ancestry of sequence points.

ARG: Trace the ancestry of sequences

Other Genealogical Structures are possible network, language merging, population splitting

Recombination

1 meiosis

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

Recombination:Gene Conversion:

•Total Haploid length males: 25.9 M - females: 44.6 M.

•Gene conversions 1-2 orders higher. Length 300-2000 pb.

Mutations and Mutation Rates

1 mitosis or generation

Average Number of Mitoses

Per Male generation (15:35 .. 20:150)

Per Female generation: ~24

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

• Single nucleotide substitutions: ~10-7

• Microsatellites (~100.000): ~10-2

• Small insertion deletions: ~10-8

A A A C C A A A C C A A A C C

Selection: Positive & Negative

Coalescent Issues1. 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

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

Our relationship to the great Apes.From Nei,2003

HumansChimp Pygmee Chimp Gorilla Orangutan

13 Myr

7 Myr

5.5 Myr

1 Myr

Ancestral Population of Human and Chimp

Human Chimp GorillaNow

5 Myr

7 Myr

H C

G eNteSpecieTreeGeneTreeP 2/3/2)( −=≠

Example: Chen & Li (2001) 53 triads: 31 (H,C), 10 (H,G) & 11 (C,G)

Out-of-Africa and different degrees of replacements

AsiaAfricaEurope AsiaAfricaEurope AsiaAfricaEurope

Total replacement No replacement Partial replacement

80-130 Kyr 80-130 Kyr 80-130 Kyr

1-1.2 Myr1-1.2 Myr1-1.2 Myr

Example: Takahata (2001) found data could be explained by total replacement.

Allele Frequencies and Principal ComponentsCavalli-Sforza,2001

1. Agriculture 6-10 Kyr

2. Greek Colonisation 3 Kyr

3. Retraction of the Basques

4. Uralic People

5. Horse domestication

•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,...

Time slices

Population

N1

1 2 1 2 1 2 1 2 1 2

Tim

e

All positions have found a common ancestors

All positions have found a common ancestors on one sequence

S– number of Segments E(S) = 1 +

Number of genetic ancestors to the Human Genome

sequence

time

R

R

R

C

C

C

Statements about number of ancestors are much harder to make.

Wiuf conjectured ~/ln()

Simulations

A randomly picked ancestor: (ancestral material comes in batteries!)

0

0 52.000

260 Mb

06890 8360

7.5 Mb

*35

0 30kb

*250

Parameters used 4Ne 20.000 Chromos. 1: 263 Mb. 263 cM

Chromosome 1: Segments 52.000 Ancestors 6.800

All chromosomes Ancestors 86.000Physical Population. 1.3-5.0 Mill.

Applications to Human Genome (Wiuf and Hein,97)

Many sampled alleles relative to NeWakeley03, Pitman, Schweinberg

1. Simultaneous Events 2. Multifurcations.3. Underestimation of Coalescent Rates

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

*

Pedigree Issues

i. Icelandic Pedigree

ii. Theoretical Models

Icelandichttp://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.

Chinesehttp://demography.anu.edu.au/People/Staff/zhongwei.html

Mormonshttp://genealogy-mormons.com/

Burke’s British Peeragehttp://www.burkes-peerage.net/sites/wars/sitepages/home.asp

Quebec FrenchHeyer and Tremblay, 1998 PNAS

1972

2002

1848

1892

Year

2

2

3

1

1 1 11

1

1

2

2

2

Ancestor cohort

Contemporary cohort

Icelandic Genealogies Helgason, 2003

Total Genealogy

Males onlyFemales only

Of (June 2002) 276,00 Icelanders 131,060 born after 1972 was traced back.

77.9%

22.1%

N = 31,817 N = 31,659

N = 66,910N = 64,150

8.3%

91.7% 86.2%

13.8%

73.9%

26.1%

g = 4.3

g = 3.8

Ancestral cohort born 1848-1892

Descendant cohortborn after 1972

Matrilines Patrilines

Ancestral cohort born 1698-1742

Descendant cohortborn after 1972

PatrilinesN = 18,023

10.3%

89.7%

N = 66,910

29.3%

70.7%

g = 7.9

g = 8.8

N = 20,443

Matrilines

6.6%

93.4%

61.8%

38.2%

N = 64,150

Icelandic Genealogies Helgason, 2003

Backtracable

Ancestors to 1972 cohort

25 50 75 100

No. of descendants

5%

10%

15%

20%

25%

Percent of ancestors

25 50 75 100

No. of descendants

Matrilines Patrilines

25 50 75 100 125 150 175 200 225 250 275 300 325 350 375

No. of descendants

2.5%

5.0%

7.5%

10.0%

12.5%

15.0%

Percent of ancestors

25 50 75 100 125 150 175 200 225 250 275 300 325 350 375

No. of descendants

Matrilines Patrilines

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

1700 1750 1800 1850 1900 1950 2000

Birth year of parent

Average number of offspring Patrilines

Matrilines

20

25

30

35

40

45

1700 1750 1800 1850 1900 1950 2000

Birth year of individual

Age of parent (years)

Patrilines

MatrilinesIcelandic

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.

Finding Ancestral Individuals.Joe Chang 1999 Dec. Adv. Appl. Prob.

Fin

din

g (

Gre

at)k

Gra

nd

Par

ents

.

Let T be the time, when somebody was everybody’s ancestor. Changs’ result: lim T*/log2(N) =1 prob. 1

NOW0

1

2

3

4

5

6

7

8

9

10

11

Combining Ancestral Individuals and the Coalescent Wiuf & Hein, 2000.

Unify the two processes:

Sample more individuals

Let each have p parents. ( p – possibly stochastic >= 1).

Result: A discontinuity at 1.

For p>1 change log2logp

Comment: Genetic Ancestors is a vanishing set within Genealogical Ancestors.

Fin

din

g C

om

mo

n A

nce

sto

rs.

NOW

Derrida

∑=+γγ

αγ

αγ

of children '' )(

2

1)1( GwGwRecursion:

Initialization:

α individual, γ ancestor in tree, w - weight probability that uni. random path leads to γ.

G

G +1

γααγ δ ,)0( =w

number. offspring expected is

. ,marriagea for ion DistributOffspring

m

pk

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:

⎟⎟⎠

⎞⎜⎜⎝

⎛+

⎟⎟⎠

⎞⎜⎜⎝

⎛−⎟⎟

⎠

⎞⎜⎜⎝

⎛

=

1

21

N

Ni

N

i

N

iα

)8/1,0(N

N/2-R then)( B.

N

,..1 NR NiN >−−= =α

-y.(y)drift malinfinitesi and 1/4 (y) variancemalinfinitesi withprocess

Uhlenbeck -Ornstein toconverges (t)S ).(ˆ:(t)S and 2/)(

:)(ˆ C. NN

==

=−

=

μσ

tRNNtR

tR NN

0

y

Non-Contributing AncestorsKevin Donnelly, 1983 TPB

….1 22 y

x….

1 22 y

x

No Recombination: Recombination:

0 1

2k

211

k

Gen

eration

:

An

cestors:

1 22 y1 22 x

46 packets

46 packets

46 packets

46 packets

<≈72 + 46 packets

< ≈k*72 + 46 packets

….1 22 y

x….

1 22

x

x

Non-Contributing AncestorsYun song- pers.comm., 2003 Kevin Donnelly, 1983

Bac

k in

Tim

e

1

2

4

8

16

32

64

128

256

512

Fro

m Y

un

So

ng

The probability of

1. Any non-contributing ancestor

2.That a randomly chosen ancestors is non-contributing

Pedigree Inference

Three Processes

1. Choosing Parents

2. Recombination

3. The Mutational Process

Fro

m Y

un

So

ng

Prior on Pedigrees

Mother Father

Posterior on Pedigrees

Elston-Stewart (1971) -Temporal Peeling Algorithm

Lander-Green (1987) - Genotype Scanning Algorithm

Probability of data given pedigree

Inheritable phenomena

Genetic Material

Sequences

“Allele Frequencies”

Language

Culture

Pathogens

Pests

Pets

Morphological Characters

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 populations:East 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

A. Maori is east asian.

B. Inuit is Euro1 + Euro2

C. South African Afr2

D. English

Cavalli- Sforza: Language TreesCavalli-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.

Historical LinguisticsWilliam 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.

Home sapiens sapiens 100-70 Kyr

AfricanKhoisan

Niger-Kordofanian

Nilo-Saharan

Afro-Asiatic

Kartvelian

Dravidian

Indo-European

Uralic

Altaic

Eskimo-Aleut

Chukchi-Kamchatkan

Amerind

Na-Dene

Sino-Tibetan

Caucasian/Basque/Burushaski

Austronesian

Daic

Miao-Yao

Austro-Asiatic

Indo-Pacific

Australian

Pacific

Austric

Asian 70-50 Kyr

Eurasian 60-40 Kyr

Austro-Tai

Congo-Saharan

Eurasiatic 20-10 KyrEurasion/American 40-20 Kyr

Dene-Caucasian 40-20 Kyr

Dene-Caucasian 40-20 Kyr

Global PhylogenyCavalli-Sforza,2001

Ruhlen, 1994

Afghan

Baluchi

Persian

Osetic

Bengali

Hindi

Punjabi

Marathi

Nepali

Kashmiri

Singhalese

Breton

Welch

Irish

Bulgarian

Macedonian

Serbo Croatian

Belorussian

Ukranian

Polish

Chech

Russian

Slovenian

Latvian

Lithuanian

French

Walloon

Italian

Ladin

Portugese

Spanish

Sardinian

Rumanian

Danish

Swedish

Riksmaal

Faraoese

Icelandic

Dutch

German

Frisian

English

Greek

Armenian

Albanian

Germ

anic

Celtic

Ro

man

ceS

lavic

600070009000 8000 5000 4000 3000 2000 1000

Indo-European Language Trees Dyen, Kruskal & Black, 1992

Piazza, Cavalli-Sforza, 2001

Germanic Language TreesFrom Embleton, 1986

English

Pennsylvanian German

Dutch

Yiddish

German

Hamburg Lower Saxony

Danish

Swedish

Icelandic

Norwegian

Faraoese

Tok Pisin

Africaans

Frisian

Flanders

TrS

1803

1540

1051

1842

246

1941051

1239

1476

1558

1051

1423 1668

12341025

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