Human Genetic Variations

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Human Genetic Variations
Genetic Tales by Andrea Branzi
2nd Lecture, October 25th 2009
Itai Yanai Department of Biology Technion
Israel Institute of Technology
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Human Genetic Variations

• The genetic basis of human variation
• The basics of population genetics
• No evolution - Hardy-Weinberg equilibrium
• Natural selection
• Genetic drift
• A very brief genetic history of humans

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GATCTACCATGAAAGACTTGTGAATCCAGGAAGAGAGACTGACTGGGCAA
CATGTTATTCAGGTACAAAAAGATTTGGACTGTAACTTAAAAATGATCAA
ATTATGTTTCCCATGCATCAGGTGCAATGGGAAGCTCTTCTGGAGAGTGA
GAGAAGCTTCCAGTTAAGGTGACATTGAAGCCAAGTCCTGAAAGATGAGG
AAGAGTTGTATGAGAGTGGGGAGGGAAGGGGGAGGTGGAGGGATGGGGAA
TGGGCCGGGATGGGATAGCGCAAACTGCCCGGGAAGGGAAACCAGCACTG
TACAGACCTGAACAACGAAGATGGCATATTTTGTTCAGGGAATGGTGAAT
TAAGTGTGGCAGGAATGCTTTGTAGACACAGTAATTTGCTTGTATGGAAT
TTTGCCTGAGAGACCTCATTGCAGTTTCTGATTTTTTGATGTCTTCATCC
ATCACTGTCCTTGTCAAATAGTTTGGAACAGGTATAATGATCACAATAAC
CCCAAGCATAATATTTCGTTAATTCTCACAGAATCACATATAGGTGCCAC
AGTTATCCCCATTTTATGAATGGAGTTheGeneticBasisofHumanVa
riationGATGAAAACCTTAGGAATAATGAATGATTTGCGCAGGCTCACC
TGGATATTAAGACTGAGTCAAATGTTGGGTCTGGTCTGACTTTAATGTTT
GCTTTGTTCATGAGCACCACATATTGCCTCTCCTATGCAGTTAAGCAGGT
AGGTGACAGAAAAGCCCATGTTTGTCTCTACTCACACACTTCCGACTGAA
TGTATGTATGGAGTTTCTACACCAGATTCTTCAGTGCTCTGGATATTAAC
TGGGTATCCCATGACTTTATTCTGACACTACCTGGACCTTGTCAAATAGT
TTGGACCTTGTCAAATAGTTTGGAGTCCTTGTCAAATAGTTTGGGGTTAG
CACAGACCCCACAAGTTAGGGGCTCAGTCCCACGAGGCCATCCTCACTTC
AGATGACAATGGCAAGTCCTAAGTTGTCACCATACTTTTGACCAACCTGT
TACCAATCGGGGGTTCCCGTAACTGTCTTCTTGGGTTTAATAATTTGCTA
GAACAGTTTACGGAACTCAGAAAAACAGTTTATTTTCTTTTTTTCTGAGA
GAGAGGGTCTTATTTTGTTGCCCAGGCTGGTGTGCAATGGTGCAGTCATA
GCTCATTGCAGCCTTGATTGTCTGGGTTCCAGTGGTTCTCCCACCTCAGC
CTCCCTAGTAGCTGAGACTACATGCCTGCACCACCACATCTGGCTAGTTT
CTTTTATTTTTTGTATAGATGGGGTCTTGTTGTGTTGGCCAGGCTGGCCA
CAAATTCCTGGTCTCAAGTGATCCTCCCACCTCAGCCTCTGAAAGTGCTG
GGATTACAGATGTGAGCCACCACATCTGGCCAGTTCATTTCCTATTACTG
GTTCATTGTGAAGGATACATCTCAGAAACAGTCAATGAAAGAGACGTGCA
TGCTGGATGCAGTGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCCAA
GGTGGGAGGATCGCTTAAACTCAGGAGTTTGAGACCAGCCTGGGCAACAT
GGTGAAAACCTGTCTCTATAAAAAATTAAAAAATAATAATAATAACTGGT
GTGGTGTTGTGCACCTAGAGTTCCAACTACTAGGGAAGCTGAGATGAGAG
GATACCTTGAGCTGGGGACTGGGGAGGCTTAGGTTACAGTAAGCTGAGAT
TGTGCCACTGCACTCCAGCTTGGACAAAAGAGCCTGATCCTGTCTCAAAA
AAAAGAAAGATACCCAGGGTCCACAGGCACAGCTCCATCGTTACAATGGC
CTCTTTAGACCCAGCTCCTGCCTCCCAGCCTTCT
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Human Genetic Variation
With the exception of monozygotic twins,
every one of us is genetically different
from every other human who ever lived. 
http//www.childrenofsalem.com/days/kids/ericbran/
ericbran1.html
American Express 1990 Advertisement
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The evolution of human skin color
Predicted skin color annual average UVMED
(0.1088)72.7483.
Jablonski Chaplan. Journal of Human Evolution
(2000) 39, 57106 Jablonski. Annu. Rev.
Anthropol. 2004. 33585623
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Genetic variation to drug responses
Because of genetic differences, different people
respond differently to the same drug.

• Example
• In the 1950s, anaesthestists began using the
  muscle relaxant succinylcholine
• A small proportion of patients went into
  life-threatening breathing arrest.
• Succinylcholine is normally metabolized by
  cholinesterase but in 1 out of 2,500 people carry
  two defective copies of the gene for this enzyme

See http//www.mdbrowse.com/Druginf/S/succinylcho
line.htm
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Genetic diseases
Online Mendelian Inheritance in Man (OMIM)
A catalog of human genes and genetic disorders
For example 603903 - SICKLE CELL ANEMIA
www.ncbi.nlm.nih.gov/entrez/query.fcgi?dbOMIM
http//www.blc.arizona.edu/courses/181gh/rick/huma
n_genetics/jpegs/cells.jpg
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The phenotype is an interplay between genes and
environment
High elevation, 3,050 meters, in the mountains
Intermediate elevation, 1,400 meters, in the
foothills of the Sierra Nevada
For example, a plant that grows short in one
elevation grows tall in another
Low elevation, 30 meters above sea level
Growth of clones of 7 genetically different
plants of Achillea millefolium grown at 3
different elevations
J. Clausen, D. D. Keck, and W.W. Heisey,
Experimental Studies on the Nature of Species,
vol 3 Environmental Responses of Climatic Races
of Achillea. Carnegie Institution of Washington
Publication 581 (1958) 1-129 Suzuki et al. An
introduction to Genetic Analysis (1996).
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Whose genome was sequenced?
International Human Genome Sequencing Consortium
The human genome reference sequence does not
represent an exact match for any one person's
genome.
The draft genome is composed of the DNA of an
estimated 10 to 20 anonymous individuals across
different racial and ethnic groups.
IHGSC. Nature (2001) 409 860-921
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Whose genome did Celera sequence?
Supposedly
African-American
Asian-Chinese
Hispanic-Mexican
Caucasian
Caucasian
Actually
Celeras genome is Craig Venters
Science v. 291, pp 1304-1351
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How are genomes of individuals different?
SNP
Nature 409, 822 - 823 (2001)
More than 90 of the differences take the form of
substitutions at a single base. These are called
single nucleotide polymorphisms (SNP)
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The Genetic Basis for Human Variation
Derived from dbSNP release 119 http//www.ncbi.nlm
.nih.gov/SNP/
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How similar are a given two sequences in a
population?
Introducing p, the nucleotide diversity
1. Average number of pairwise nucleotide
differences between seqs.
of differences between sequences
of pairs
2. Normalize to the length of the sequences (L)
Example
(1/3)(314) 8/3 (8/3)/12 0.222 A pair of
sequences are on average 22.2 different
1. ACAGCATTAGCA 2. ATAGCAATAGCT 3. ATAGCAATACCT
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Any 2 human genomes are roughly 99.9 identical
On average 0.1
Chr - chromosome n - Number of samples
examined bp - Number of basepairs sequences S -
Number of polymorphic sites p - Nucleotide
divergence
Przeworski, M., et al. (2000) Trends Genet 16,
296-302.
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Variation is the splice of life
If 1. Any two genomes are roughly 99.9
identical and 2. A genome is 3.2 billion
base pairs long Then Every two genomes have
3.2 million differences (SNPs)
(remember also that each individual has two
genomes)
Kruglyak and Nickerson Nature Genetics (2001) 27
234
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How many SNPs are born in one generation?
Number of genomes N 14109 (twice the number
of people, why?) Mutation rate m
210-8 per base-pair per generation (gen) New
mutations Nm 280 per base-pair per
generation In other words Every base gets
mutated in 280 individuals each gen However the
overwhelming majority of these will be very rare.
We set a minimal frequency for a polymorphism
at 1 in the population (below this frequency
its just a mutation ?)
Kruglyak and Nickerson Nature Genetics (2001) 27
234
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How many SNPs are there in human populations?
Occurrence of SNPs in the human population
(based upon the classical neutral theory of
population genetics)
It can be shown (assuming a few things) that the
number of sites Sf with alleles at frequency f
in the population is related to the number of
sites S2 that vary between 2 haploid genomes by
approximately
Let S2 3.2109bp/1,331bp f 0.01
Kruglyak and Nickerson Nature Genetics (2001) 27
234
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How are the frequencies of the SNPs distributed?
Identified 35,989 SNPs in a sample of 20 copies
of chromosome 21.
Patil et al. Science (2001) 2941719-1723
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Where are the SNPs found?
Most SNPs are not found in the coding regions
and, consequently, are inconsequential.
Could make a difference
Probably dont make a difference
http//www.ncbi.nlm.nih.gov/SNP/snp_summary.cgi
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The SNP database today
The 1000 Genomes Project submitted 17.3M
SNPs The 2008 SNP Submissions for the James
Watson Genome totaled 3,542,364 The 2008
SNP Submissions for the J. Craig Venter Genome
totaled 4,018,050 The 2008 SNP
Submissions for the Individual Chinese Genome
totaled 5,077,954 The 2008 SNP
Submissions for the Individual Korean Genome
totaled 1,750,224
Derived from dbSNP release 130 http//www.ncbi.nlm
.nih.gov/SNP/
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SNPs arent everything Introducing Copy Number
Variations
Redon et al. Nature 2006
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Copy Number Variations are ubiquitous in the
human genome

• Examining 270 individuals.
• A total of 1,447 copy number variable regions
  (CNVRs)
• Encompass 360 megabases (12 of the genome)

Redon et al. Nature 2006
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Copy Number Variations are ubiquitous in the
human genome
The number of genome structural variants (gt1 kb)
that distinguish genomes of different individuals
is at least on the order of 600900 per
individual.
J.O. Korbel et al., Science 318(2007), pp. 420426
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Humans are 99.5 identical (not 99.9)
2,894,929
939,799
10,000,000
(total genome)
13,834,728
2,809,547,336 0.5
S. Levy, PLoS Biol 5 (2007), p. e254
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GATCTACCATGAAAGACTTGTGAATCCAGGAAGAGAGACTGACTGGGCAA
CATGTTATTCAGGTACAAAAAGATTTGGACTGTAACTTAAAAATGATCAA
ATTATGTTTCCCATGCATCAGGTGCAATGGGAAGCTCTTCTGGAGAGTGA
GAGAAGCTTCCAGTTAAGGTGACATTGAAGCCAAGTCCTGAAAGATGAGG
AAGAGTTGTATGAGAGTGGGGAGGGAAGGGGGAGGTGGAGGGATGGGGAA
TGGGCCGGGATGGGATAGCGCAAACTGCCCGGGAAGGGAAACCAGCACTG
TACAGACCTGAACAACGAAGATGGCATATTTTGTTCAGGGAATGGTGAAT
TAAGTGTGGCAGGAATGCTTTGTAGACACAGTAATTTGCTTGTATGGAAT
TTTGCCTGAGAGACCTCATTGCAGTTTCTGATTTTTTGATGTCTTCATCC
ATCACTGTCCTTGTCAAATAGTTTGGAACAGGTATAATGATCACAATAAC
CCCAAGCATAATATTTCGTTAATTCTCACAGAATCACATATAGGTGCCAC
AGTTATCCCCATTTTATGAATGGAGTTheBasicsofPopulationGen
eticsGATGAAAACCTTAGGAATAATGAATGATTTGCGCAGGCTCACCTG
GATATTAAGACTGAGTCAAATGTTGGGTCTGGTCTGACTTTAATGTTTGC
TTTGTTCATGAGCACCACATATTGCCTCTCCTATGCAGTTAAGCAGGTAG
GTGACAGAAAAGCCCATGTTTGTCTCTACTCACACACTTCCGACTGAATG
TATGTATGGAGTTTCTACACCAGATTCTTCAGTGCTCTGGATATTAACTG
GGTATCCCATGACTTTATTCTGACACTACCTGGACCTTGTCAAATAGTTT
GGACCTTGTCAAATAGTTTGGAGTCCTTGTCAAATAGTTTGGGGTTAGCA
CAGACCCCACAAGTTAGGGGCTCAGTCCCACGAGGCCATCCTCACTTCAG
ATGACAATGGCAAGTCCTAAGTTGTCACCATACTTTTGACCAACCTGTTA
CCAATCGGGGGTTCCCGTAACTGTCTTCTTGGGTTTAATAATTTGCTAGA
ACAGTTTACGGAACTCAGAAAAACAGTTTATTTTCTTTTTTTCTGAGAGA
GAGGGTCTTATTTTGTTGCCCAGGCTGGTGTGCAATGGTGCAGTCATAGC
TCATTGCAGCCTTGATTGTCTGGGTTCCAGTGGTTCTCCCACCTCAGCCT
CCCTAGTAGCTGAGACTACATGCCTGCACCACCACATCTGGCTAGTTTCT
TTTATTTTTTGTATAGATGGGGTCTTGTTGTGTTGGCCAGGCTGGCCACA
AATTCCTGGTCTCAAGTGATCCTCCCACCTCAGCCTCTGAAAGTGCTGGG
ATTACAGATGTGAGCCACCACATCTGGCCAGTTCATTTCCTATTACTGGT
TCATTGTGAAGGATACATCTCAGAAACAGTCAATGAAAGAGACGTGCATG
CTGGATGCAGTGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCCAAGG
TGGGAGGATCGCTTAAACTCAGGAGTTTGAGACCAGCCTGGGCAACATGG
TGAAAACCTGTCTCTATAAAAAATTAAAAAATAATAATAATAACTGGTGT
GGTGTTGTGCACCTAGAGTTCCAACTACTAGGGAAGCTGAGATGAGAGGA
TACCTTGAGCTGGGGACTGGGGAGGCTTAGGTTACAGTAAGCTGAGATTG
TGCCACTGCACTCCAGCTTGGACAAAAGAGCCTGATCCTGTCTCAAAAAA
AAGAAAGATACCCAGGGTCCACAGGCACAGCTCCATCGTTACAATGGCCT
CTTTAGACCCAGCTCCTGCCTCCCAGCCTTCT
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A locus is a region on the chromosomes
One locus
http//www.ncbi.nlm.nih.gov/mapview/
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An allele is a variation at a locus
For example in the same locus we may have
Allele 1
CAGTAATTTGCTTGTATGGAATTTTGCCTGAGAGACCTCATTGCA..GTT
TCTGATTTTTTGATGTCTTCATCCATCACTGTCCTTGTCAAATAGTTT
GGAACAGGTATAATGATCACAATAACCCCAAGCATAATATTTCGTTAATT
CTC
Allele 2
CAGTAATTTGCTTGTATGGAATTTTGCCTGAGAGACCTCATTGCA..GTT
TCTGATTTTTTGATGTCTTCAGCCATCACTGTCCTTGTCAAATAGTTT
GGAACAGGTATAATGATCACAATAACCCCAAGCATAATATTTCGTTAATT
CTC
allele frequency is the proportion of a certain
allele within a population.
http//www.micro.utexas.edu/courses/levin/bio304/p
opgen/popgen.html
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The Great Obsession of Population Genetics
Evolution is the change in frequencies of
genotypes through time.
What evolutionary forces could have led to such
divergence between individuals within the same
species?
Gillespie, A primer to Population Genetics
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http//wanderwear.safeshopper.com/images/20jb0nx.g
if
The gene pool the set of all alleles at all loci
in a population
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What is the distribution of genotypes?
For two alleles ( and ) we have three
genotypes Let p the frequency of A ,
and q the frequency of a .
(p q 1) What is the frequency of ?
AA
Aa
aa
A
a
AA
Aa
aa
AA
aa
Aa
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The Hardy-Weinberg equilibrium
p2 2pq q2 1 (p q)2 1 p (p2 pq)/(p2
2pq q2) q (q2 pq)/(p2 2pq q2) p is
the frequency of p in the next generation
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Hardy-Weinberg equilibrium

• Assumptions of the standard random-mating model
• random mating
• no mutation
• no migration
• no selection
• the population size is infinitely large

Frequencies for some alleles can be very close to
the equilibriumvalues
http//www.micro.utexas.edu/courses/levin/bio304/p
opgen/popgen.html
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Hardy-Weinberg equilibrium
Given a p of 0.2, the frequency of a/a should be
this
not in equilibrium
genotype frequency
allelic frequency
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Population achieves Hardy-Weinberg equilibrium
after one generation
Not in equilibrium
AA Aa aa 0.6 0 0.4
Next generation
In equilibrium AA Aa aa 0.36 0.48 0.16
AA
Aa
aa
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The Standard Model
p 0.6 q 0.4
AA
Aa
aa
(Selection step)
p 0.6 q 0.4
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Models of Natural Selection Fitness Score
AA Aa aa w11 w12 w22 Neutral 1 1 1 Codomi
nance 1 1s 12s Dominance 1 1s 1s Recessive
1 1 1s Balancing 1 1s 1
Selection does not achieve balance in one round
like H.W.
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Change in frequency due to selection according
to a deterministic model
Previously, we calculated q in the next
generation as
As we have seen this reduces simply to q
Adding a separate weight to each genotype is one
way to impose selection biasness of the
genotypes
38
Change in frequency due to selection
It can be easily shown that
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Codominance selection
w11 w12 w22 Weights 1 1s 12s
Remember that
If s is small denominator can be approximated to
be 1
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Dominance selection
w11 w12 w22 Weights 1 1s 1s
If s is small denominator can be approximated to
be 1
42
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43
Recessive selection
w11 w12 w22 Weights 1 1 1s
If s is small denominator can be approximated to
be 1
44
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45
Balancing Selection
w11 w12 w22 Weights 1 1 s 1
If s is small denominator can be approximated to
be 1
46
(No Transcript)
47
Genetic drift
Frequency of
0.5
0.6
0.7
0.8
0.9
1.0
48
A stochastic model for evolution
N individuals in a finite population (stays
constant)
.
Next generation is a composition of previous
population According to random sampling with
replacement
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The fate of a mutant in a infinite population
R.A. Fisher. The distribution of gene ratios for
rare mutations (1930)

• If a mutant has a selective advantage of 0.01,
  there is 78 chance for it to be lost in the
  first seven generations.
• And a 2 chance of spreading to the entire
  population.
• Most beneficial mutations do not fix in the
  population!

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Modeling Genetic Drift
Using the Binomial distribution, in a population
of size 2N with two alleles with frequencies p
and q, the probability that p will become i/2N
and q will become (2N-i)/2N is
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Genetic drift in theoretical populations
Probability distribution of A allele in a
population of 100 and random sampling each
generation. Initial frequency of A was set
0.5. The histograms summarize 10,000 simulations.
54
What is the probability that a new mutation will
be fixed in the population?
Population 2N (assuming a diploid
population) Initial frequency
1/2N Probability of fixation ???
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(No Transcript)
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How long does it take for a new mutation to
become fixed?
Graur Li. Fundamentals of Molecular Evolution
(2000)
57
How long does it take for a new mutation to
become fixed?
Kimura and Ohta showed that
For a neutral mutation
4N generations
For a mutation with a selective advantage
(2/s)ln(2N) generations
For this analysis diffusion equations were
invoked, But we will not have a chance to go
into that.
58
The universe of family names has many endangered
species!
The analogy with family names

• The passing on of family names is analogous to
  that of alleles.
• In China, family names have been passed for over
  2,000 years
• Entire small villages sometimes have same last
  name.
• Although there are a billion people, there are
  only 100 names
• Family names with a small frequency are in danger
  of extinction.

http//www.ucl.ac.uk/ucbhjow/b241/b3pop1.html
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Mutations are the engines of variation
Without new variations, evolution would come to a
halt all individuals would become the same
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GATCTACCATGAAAGACTTGTGAATCCAGGAAGAGAGACTGACTGGGCAA
CATGTTATTCAGGTACAAAAAGATTTGGACTGTAACTTAAAAATGATCAA
ATTATGTTTCCCATGCATCAGGTGCAATGGGAAGCTCTTCTGGAGAGTGA
GAGAAGCTTCCAGTTAAGGTGACATTGAAGCCAAGTCCTGAAAGATGAGG
AAGAGTTGTATGAGAGTGGGGAGGGAAGGGGGAGGTGGAGGGATGGGGAA
TGGGCCGGGATGGGATAGCGCAAACTGCCCGGGAAGGGAAACCAGCACTG
TACAGACCTGAACAACGAAGATGGCATATTTTGTTCAGGGAATGGTGAAT
TAAGTGTGGCAGGAATGCTTTGTAGACACAGTAATTTGCTTGTATGGAAT
TTTGCCTGAGAGACCTCATTGCAGTTTCTGATTTTTTGATGTCTTCATCC
ATCACTGTCCTTGTCAAATAGTTTGGAACAGGTATAATGATCACAATAAC
CCCAAGCATAATATTTCGTTAATTCTCACAGAATCACATATAGGTGCCAC
AGTTATCCCCATTTTATGAATGGAGTReadingHumanHistoryInscr
ibedInOurGenomesGATGAAAACCTTAGGAATAATGAATGATTTGCGC
AGGCTCACCTGGATATTAAGACTGAGTCAAATGTTGGGTCTGGTCTGACT
TTAATGTTTGCTTTGTTCATGAGCACCACATATTGCCTCTCCTATGCAGT
TAAGCAGGTAGGTGACAGAAAAGCCCATGTTTGTCTCTACTCACACACTT
CCGACTGAATGTATGTATGGAGTTTCTACACCAGATTCTTCAGTGCTCTG
GATATTAACTGGGTATCCCATGACTTTATTCTGACACTACCTGGACCTTG
TCAAATAGTTTGGACCTTGTCAAATAGTTTGGAGTCCTTGTCAAATAGTT
TGGGGTTAGCACAGACCCCACAAGTTAGGGGCTCAGTCCCACGAGGCCAT
CCTCACTTCAGATGACAATGGCAAGTCCTAAGTTGTCACCATACTTTTGA
CCAACCTGTTACCAATCGGGGGTTCCCGTAACTGTCTTCTTGGGTTTAAT
AATTTGCTAGAACAGTTTACGGAACTCAGAAAAACAGTTTATTTTCTTTT
TTTCTGAGAGAGAGGGTCTTATTTTGTTGCCCAGGCTGGTGTGCAATGGT
GCAGTCATAGCTCATTGCAGCCTTGATTGTCTGGGTTCCAGTGGTTCTCC
CACCTCAGCCTCCCTAGTAGCTGAGACTACATGCCTGCACCACCACATCT
GGCTAGTTTCTTTTATTTTTTGTATAGATGGGGTCTTGTTGTGTTGGCCA
GGCTGGCCACAAATTCCTGGTCTCAAGTGATCCTCCCACCTCAGCCTCTG
AAAGTGCTGGGATTACAGATGTGAGCCACCACATCTGGCCAGTTCATTTC
CTATTACTGGTTCATTGTGAAGGATACATCTCAGAAACAGTCAATGAAAG
AGACGTGCATGCTGGATGCAGTGGCTCATGCCTGTAATCTCAGCACTTTG
GGAGGCCAAGGTGGGAGGATCGCTTAAACTCAGGAGTTTGAGACCAGCCT
GGGCAACATGGTGAAAACCTGTCTCTATAAAAAATTAAAAAATAATAATA
ATAACTGGTGTGGTGTTGTGCACCTAGAGTTCCAACTACTAGGGAAGCTG
AGATGAGAGGATACCTTGAGCTGGGGACTGGGGAGGCTTAGGTTACAGTA
AGCTGAGATTGTGCCACTGCACTCCAGCTTGGACAAAAGAGCCTGATCCT
GTCTCAAAAAAAAGAAAGATACCCAGGGTCCACAGGCACAGCTCCATCGT
TACAATGGCCTCTTTAGACCCAGCTCCTGCCTCCCAGCCTTCT
61
Out of Africa
Scientific American, August 1999)
Modern humans arose in Africa and replaced other
human species across the globe.
62
Out of Africa again and again
Templeton, A. Nature 416 (2002) 45 - 51
Itai Yanai, 2003
63
Archaeological reconstructions of major human
migrations

• How did agriculture spread 10,000 years ago?
• According to the spread of ideas and artifacts?
  Or,
• According to the spread of the farmers?

• Genotypes at 95 alleles were determined for
  several hundred individuals from 26 present-day
  European populations
• Allele frequencies among populations were
  summarized by principal components.
• The first component of principle components
  recovered 28 of the variation in the data
• The first five components explained 75 of
  European genetic variation.

L. L. Cavalli-Sforza et al. The History and
Geography of Human Genes (1994)
64
1st principle component shows migration from the
Middle East
The most important genetic landscape for Europe
faithfully reflects the spread of agriculture in
Neolithic times.
L. L. Cavalli-Sforza et al. The History and
Geography of Human Genes (1994)
In particular, the values of the most important
component reflected the paths of Neolithic
farmers from the Middle East (i) westward across
the Mediterranean to present-day Greece, Italy,
and Spain, and (ii) northwest through Europe, to
present-day Germanic-speaking areas of northern
Germany, northwestern Europe, and England.
65
2nd principle component

• Genetic adaptation to the cold of northern
  Europe?
• Reflects distribution of the Uralic family of
  languages?
• The result of a single large migration?

L. L. Cavalli-Sforza et al. The History and
Geography of Human Genes (1994)
66
Migrations from the steppes of the lower Volga
and Don rivers by the early pastoral nomads who
first domesticated the horse could be represented
by the third component.
L. L. Cavalli-Sforza et al. The History and
Geography of Human Genes (1994)
67
Percentage of human genetic variation within and
between populations.
R.A.Brown,G.J.Armelagos,Evol.Anthropol.10 ,34
(2001).
68
Percentage of human genetic variation within and
between populations.
Owens and King Science (1999) 286 451-453.
An average population from anywhere in the world
includes 85 of all human variation at autosomal
loci and 81 of all human variation in mtDNA
sequences. Differences among populations from the
same continent contribute another 6 of
variation only 9 to 13 of genetic variation
differentiates populations from different
continents
69
Most alleles are geographically widespread
377 autosomal microsallelite loci 1056
individuals from 52 populations from seven regions
Rosenberg et al. Science Dec 20 2002 2381-2385.
(sup)
70
No major genetic differences across races
The possibility that human history has been
characterized by genetically relatively
homogeneous groups (races), distinguished by
major biological differences, is not consistent
with genetic evidence . . .. The myth of major
genetic differences across races in nonetheless
worth dismissing with genetic evidence.
Owens and King Science (1999) 286 451-453.