eeb chapter #9

7/28/2019 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

14.8


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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?

14.8

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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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


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.


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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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

.13


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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



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Unlike HbS, HbCprovides more protection against malaria in the

homozygous state (CC)than in heterozygous state (AC)


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.

eeb chapter #9

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