Download - EEB Chapter #9
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A. Patterns of Human Genetic Variation
IV. Evolution of human populations
Many traits and genes show large differences
in and among human populations around the world.
Key Question:
How is such variation distributed
is there more variation within or among
different human populations?
Distribution of Human Genetic Variation
Variation within = 0%Variation between = 100%
Variation within= 100%Variation between = 0%
Variation within = 89%Variation between = 11%
Variation Within and Between Groups
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Studies of blood groups and other genetic markers show~ 10% of the total human variation exists
betweengeographic regions,with 90% existing withingeographic regions.
Variation between = 10%Variation within = 90%
Variation Between or Within Populations?
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Apportionment of Human Genetic Diversity
Genetic Divergence among Human Populations
It is used to understand the effects of genetic drift andgene flow, random evolutionary processes.
Genetic Distanceis a measure ofaverage relatedness between populations
Selection is non-random, so the genes used formeasuring genetic distance are chosen to be
evolutionarily neutral, i.e., not under selection.
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Genetic Divergence among Human Populations
Based on allele frequenciesfor 120 genes
Genetic distances toNative Americans
At smaller values,populations are more similar
At larger values, they aremore dissimilar
Genetic distanceson a phylogeny
European
Africa
Middle Eastern
East Asian
Central/Southern Asia
America
Oceania
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Geographic Distance vs. Genetic Distance
Isolation by Distance Between Human Populations
The hypothesis for the expected relationship betweengeographic distance and genetic distance is
the isolation by distance model.
Genetic similarity is assumed to be a function of gene flow,the more gene flow between two populations,
the more similar they are genetically.
The closer two populations are geographically,the more gene flow between them,and the smaller the genetic distance.
The opposite is true the farther they are apart.
Genetic Divergence
among Human Populationsexpectedwith ibd*
* ibd isolation by distance
actual genetic distances
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Morphological traitsGenetic relatednessBased on 120 genes
Contrast between genetic and phenotypic similarity
Phenotypic similarities are not necessarily a good indicator of genetic ones
Phenotypic:Skin color
GeneticRelatedness:isolation by
distance
What might be an explanation for the differences between these patterns?
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B. Natural Selection in Human Populations
Natural Selection and Disease
Natural Selection and Climate
Natural Selection and Culture Change
Tay Sachs
Cystic fibrosis
Variation among human populations for disease prevalence
phenylketonuria
Founder effect
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Natural Selection and Disease
Malaria is the strongest known force for evolutionaryselection in the recent history of the human genome.
Malaria is caused by a group of parasites in the genus Plasmodium(Protistan Kingdom, Phylum Apicomplexa)
Human malaria is mainly due to 4 species of Plasmodium.P. falciparumis the most dangerous cerebral malaria
Plasmodiumis transmitted to humans only by mosquitoes in thegenus Anopheles(over 100 species are known to be vectors).
Alternating high fevers & shaking chills,flu-like symptoms, and anemia
Natural selection and malaria
Malaria is the strongest known force for evolutionary
selection in the recent history of the human genome.
Over 200 Million people become ill each year withfalciparum malaria
30 million more are infected with other forms ofPlasmodium
Over 600 Thousand people die every year from malaria
In some regions, every member of a community may be infected
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Natural selection and malaria
Malaria is implicated as the driving force for theevolution of the most common human Mendelian diseases
The most common and familiar is sickle cell anemiadue to the hemoglobin S allele
However, there are at least 5 other known red blood cellmutations that appear to be favored against malaria
Natural selection and malaria
Plasmodiumspecies P malariaeP ovale
P vivax
Hominoids divergefrom chimps
Homosapiens
Agriculture
Blood group O inhominids
mutation from A
Mammals
Coevolution of Plasmodium falciparumand humans
Homo sapiensout of Africa
P falciparumincreased virulence
200MYA
76-160MYA
9-10MYA
27000
8MYA
3200
10000
200000
100000
80000
70000
40000
10000
4000
2000
50000
5MYA
hemoglobins S and CG6PD
ThalassemiaHb E
P falciparum(humans)P reichenowii(chimps)
P falciparumcurrent form
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(a) Frequency of sickle-cell allele (b) Distribution of malaria
Hemoglobin, Sickle Cell, and Malaria
Themost widely studied anti-malarial mutation is thehemoglobin Sallele (HbS), the sickle cell allele.
The distribution of the allele is related to theprevalence of certain forms of malaria. A person who
has two HbSalleles has sickle cell anemia.
Hemoglobin, Sickle Cell, and Malaria
As we saw previously, there is a selectiveadvantagefor heterozygous people in a malarial environment.
There is a cost to this adaptation, however an
increased proportion of individuals get sickle cellanemia, which can be itself fatal.
This is an indication of the strength of naturalselection imposed by malaria.
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Hemoglobin, Sickle Cell, and Malaria
Change in frequency of the HbSAllelein presence of malaria
Initial Smutation
AA = 88
AS= 100
SS= 14
Relativefitnesses
Sallele frequency increases very rapidly in this scenario
but it only rises to a frequency of ~13%
Relationship between death rates and frequency of Sallele
balance between
opposing selective forces
Deaths from malariaor sickle cell
alone
Deaths from malaria
and sickle cellcombined
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There are two additional structural mutations of
the -globin chain that also map geographicallyto regions where malaria is endemic.
Other hemoglobin mutations
HbEis found in Southeast Asia, up to50% frequency in some isolated populations
Malarial region
HbCis found in West Africa, with high allele frequencies inBurkina Faso and Mali, where it protects against severe malaria
Other hemoglobin mutations
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Unlike HbS, HbCprovides more protection against malaria in the
homozygous state (CC)than in heterozygous state (AC)
Other hemoglobin mutations
Because of this, HbCis projected to replace theHbSallele in malarial habitats such as Burkina Faso,
in perhaps as few as 50 generations! *
* Hedrick 2004. J Evol Biol.
More Natural Selection and Malaria
Individuals homozygous for Duffy negative allele (FY*O)are completely resistant to malaria caused by Pl. vivax.
Areas where the Duffy negative allele frequency is high,have no vivaxmalaria.
The Duffy Blood Group
FY*O
mutation
note that the mutation is actually in theregulatory region for this gene
gene
The Duffy antigen - a strong receptor for bloodcell invasion by Plasmodium vivax.
One allele, FY*Odoes not produce the antigenprotein in blood cells.
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The Duffy Blood Group
In China, there is some evidence for the reverse situation there is some evidence for strong selection for the FY *A allele
Regions ofreducedvariation
Which region on this graph is the bestpotential evidence for strong selection?
A
B
C
Distribution ofB and O
Blood Groups
ABO Blood
Groupsand malaria
Frequency of O increasesand frequency of B
decreases in Africanmalarial regions
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0.00
0.20
0.40
0.60
0.80
O A B AB
%o
fpatientswith
mildvs.severemalari
Blood Group
Mild
Severe
Natural Selection and The ABO Blood Groups
Pathirana et al. 2005. Ann. Trop. Med. & Parasit.
Possible model for Blood type O malarial advantage
Cells with A or B antigens may attach to walls of capillaries,allowing parasite to mature and release more merozoites.Blood group O cells do not attach.
Differences inblood cell adhesiveness?
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ABO Blood Type and Infectious and Noninfectious Disease
Bloodtype A is more susceptible to smallpox,type B seems more susceptible to infant diarrhea,and type O seems more susceptible to bubonic plague.
People with blood type O have a greater chance of gettingduodenal and stomach ulcers.
People with blood type A have a greater chance of gettingcertain types of cancer.
Natural Selection and the ABO Blood Groups
Natural Selection and the ABO Blood Groups
Meier Human Evolutionary Biology chap 13
Diagnosis #patients
#controls
Comparison RelativeIncidence*
Stomach cancer 55434 1852288 A : O 1.22
Colon cancer 7435 183286 A : O 1.11
Pancreatic cancer 817 108408 A : O 1.24
Duodenal ulcer 26039 407518 O : A 1.35
Gastric ulcer 22052 448354 O : A 1.17
Thromboembolism A, AB, B : O 1.60
*frequency in patients/frequency in controls
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More Natural Selection and MalariaThalassemia
Thalassemia due to deficiencies in production of -globinor -globin chains of the hemoglobin molecule.
A large number of different mutations can cause it.
Homozygous thalassemia results in severe disease - severe
anemia, enlargement of the heart, liver, and spleen, and skeletaldeformation - and can be fatal.
Heterozygotes are healthy other than mild anemia.
-hemoglobins
chains
chains-hemoglobins
Normal hemoglobinprotein
- and -ThalassemiasDespite the very strong selection against homozygotes, thalassemias are themost common Mendelian diseases of humans and a major global health
problem over 70 million people are affected.
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Malaria greatly reduces hemoglobin concentrations, causing
life-threatening anemia for children with hemoglobin below 5g/dl
Children with thalassemia produce smaller but more red bloodcells than average, maintaining hemoglobin levels.
Wambua et al 2006. PLoS Medicine 3:e158
Why is thalassemia effective against malaria?
Children 5 yrs oldor younger
- normal
- heterozygotes
- homozygotes
Thalassemias, sickle-cell and malaria
Are different anti-malarial alleles effective in combination?
A recent study looked at the joint effects of hemoglobin S and-thalassemia in Kenya, where both occur at high frequency.
Individuals who had both sickle-cell (HbAS) and -thalassemiahad malarial rates similar to individuals who had neither.
Suggests that their combined effects cancel out any benefits.