VAB11 06a Population Genetics

Population genetics

sexual reproduction genetic structure of population Hardy-Weinberg law factors disturbing Hardy-Weinberg equilibrium human populations

Population genetics

the studies of genetic structure of population the studies of events affecting population the studies of relationships inside population, relationships

between populations the studies of population dynamics in population studies, we always need a cross section

of the population

population is a collection of individuals who belong to 1 species; all these individuals occupy (share) a common area

Sexual reproduction and genetic structure of population

autogamy

allogamy inbreeding outbreeding panmixia

model of ideal population distribution of allele and genotype frequencies according to

Hardy-Weinberg law

in plants only

male & female gametes from 1 individual give rise to zygote

during few generations, autogamy leads to high level of homozygosity in offspring

generation heterozygotes (%)

homozygotes (%)

autogamy

allogamy

male & female gametes from 2 individuals give rise to zygote

allogamy


allogamy inbreeding

mating between consanguineous individuals along subsequent generations

inbreeding results in decrease of genetic heterogeneity in population it has similar effect as autogamy (but autogamy acts more rapidly)

in human, consanguineous mating is very similar to (or the same as) inbreeding


allogamy outbreeding

mating between individuals who are not closely related outbreeding results in maintenance of genetic

heterogeneity in population in human: a marrying outside one's social group


allogamy panmixia a model of ideally panmictic population:

random mating among individuals in population; individuals of the same generation mate together

individuals of all genotypes are equally fertile there is no selection among various genotypes

no mutations originate there is no migration the population is large enough

the ideally panmictic population does not exist in real

world it is a mathematical description of simplified model

Genetic structure of population

gene pool: a collection of all the alleles at a particular locus for the entire population

gene pool: for autosomal loci, the size of the gene pool is twice the number of individuals in the population

AA

AA

AA

AA

AA

Aa

Aa Aa

Aa

Aa Aa

Aa Aa

Aa

Aa

Aa Aa

Aa Aa Aa Aa

Aa Aa

Aa

Aa

Aa

Aa

Aa Aa Aa aa

AA

Genetic structure of population

is specified by allele frequencies and genotype frequencies in population: allele frequency: relative proportion of particular allele

in population genotype (phenotype) frequency: relative proportion

of particular genotype (phenotype) in population

we must distinguish 2 basically different situations if we

need to estimate allele and genotype frequencies: co-dominance & semidominance complete dominance

Genetic structure of population autosomal inheritance I. co-dominance, semidominance:

genotype & phenotype frequencies

each genotype can be distinguished from others according to its specific phenotype

the frequencies of all genotypes can be determined accurately

AA AA

Aa Aa

aa aa



phenotype frequencies are equal to corresponding genotype frequencies

we can simply count individuals of all genotypes after this, we can calculate allele frequencies:

AA

AA

AA

AA

AA Aa Aa Aa

Aa

Aa

Aa Aa Aa Aa

Aa

Aa Aa

Aa Aa Aa Aa

Aa Aa Aa

Aa Aa

Aa

Aa Aa Aa aa

AA



AA

AA

AA

AA

AA Aa Aa Aa

Aa

Aa

Aa Aa Aa Aa

Aa

Aa Aa

Aa Aa Aa Aa

Aa Aa Aa

Aa Aa

Aa

Aa Aa Aa aa

AA

frequency of allele A: 25 A 2 x 6 A +

6 individuals carry 2 alleles A (homozygotes)

total count of all alleles of the gene in the population

25 individuals carry 1 allele A (heterozygotes)


allele frequencies

we can calculate allele frequencies directly from frequencies of corresponding phenotypes:

2.n(aa)2.n(Aa)2.n(AA)n(Aa)2.n(AA)fA ++

+=

n ... number of individuals with certain phenotype

Genetic structure of population autosomal inheritance II. complete dominance:


the only one genotype that we can distinguish from others: recessive homozygotes always differ in phenotype from all other individuals

the frequency of recessive homozygotes is the only one frequency that can be determined accurately

AA AA

Aa Aa

aa aa

AA AA AA

AA

AA

Aa

Aa Aa

Aa

Aa

Aa

Aa Aa Aa

Aa

Aa Aa

Aa Aa Aa Aa

Aa Aa Aa Aa Aa

Aa

Aa Aa Aa aa

AA Aa Aa

Genetic structure of population autosomal inheritance II. complete dominance:

genotype & phenotype frequencies all other frequencies (genotype & allele frequencies)

must be calculated according to Hardy-Weinberg law

H.-W. law can be applied exactly in ideally panmictic populations (see above mentioned conditions in ideal panmixia)

although ideally panmictic population does not exist, we can apply mathematical equations of H.-W. law to common populations (the error of such calculation is usually acceptable)

Hardy-Weinberg law

Hardy-Weinberg law describes distribution of alleles and genotypes in panmictic population:

p + q = 1

p2 + 2pq + q2 = 1

allele frequencies:

genotype frequencies:

relative proportion of particular alleles in population

relative proportion of particular genotypes in population

Hardy-Weinberg law: Genotype frequencies

AA

AA

AA

AA

AA

Aa

Aa Aa

Aa

Aa

Aa

Aa Aa Aa

Aa

Aa Aa

Aa Aa Aa Aa

Aa Aa

Aa

Aa Aa

Aa

Aa Aa Aa aa

AA

relative proportion of dominant homozygotes

relative proportion of heterozygotes

+ + relative proportion of recessive homozygotes

= entire population (100 % of individuals)

p2 + 2pq + q2 = 1

Hardy-Weinberg law

the probability of allele transfer to gametes (in the context of entire population) depends on frequency of this allele in particular population

more frequent allele in population higher probability of allele transmission into offspring

Hardy-Weinberg law the probability that 2 independent events would meet together

(i.e. egg carrying particular allele would meet sperm cell with particular allele) is equal to multiplication of probabilities of occurrence of these 2 independent features

frequency of allele A

(p)

frequency of allele a

(q) frequency of allele A

(p)

frequency of AA (p2)

frequency of Aa

(pq) frequency of allele a

(q)

frequency of Aa

(pq)

frequency of aa (q2)

dominant allele frequency : p recessive allele frequency: q

probability of meeting gametes (oocyte & sperm cell) with particular alleles:

spermatozoa:

egg cells:

Hardy-Weinberg law

p2 + 2pq + q2 = 1 genotype frequencies in population:

frequency of allele A

(p)

frequency of allele a

(q) frequency of allele A

(p)

frequency of AA (p2)

frequency of Aa

(pq) frequency of allele a

(q)

frequency of Aa

(pq)

frequency of aa (q2)

H.-W. law: consequences

if there are established conditions for H-W equilibrium in population allele & genotype frequencies remain unchanged

if there is H-W equilibrium in population it is possible to calculate frequency of recessive allele from the frequency of recessive homozygotes

it is possible to calculate all other frequencies (dominant allele frequency and genotype frequencies) from the frequency of recessive allele

H.-W. law: consequences

low allele frequency in population: lower frequency of corresponding homozygotes rare alleles are found in heterozygotes mainly

(in the case of recessive disorders, most of people who have this allele are carriers only; sick people are found rarely):

allele frequency (q)

heterozygote frequency (2pq)

homozygote frequency (q2)

0,5 0,5 0,25

0,2 0,32 0,04

0,1 0,18 0,01

0,01 0,02 0,000 1

0,001 0,002 0,000 001

0,000 1 0,000 2 0,000 000 01

Simplification of H.-W. law

it can be used if the frequency of particular phenotype in population is less than 1:10 000 (rare traits or diseases): q2

H.-W. law: Gonosomal genes in population

X-linked traits (genes) 2 different situations that can be found in population:

women men


WOMEN: 3 possible genotypes (XHXH, XHXh, XhXh) allele frequencies & genotype frequencies may be

calculated according H.-W. rule (as in the case of autosomal genes)

women: recessive phenotype frequency (XhXh) : q2


MEN: 2 possible genotypes (they are hemizygotes) (XHY, XhY) probability of hemizygote (XhY) origination is equal to

probability that single allele would be inherited from mother

allele frequencies = genotype frequencies !!!

men: recessive phenotype frequency (XhY) : q

Hardy-Weinberg equilibrium

it is a state of population if there are met all conditions of ideally panmictic population

thus, H-W equilibrium is a steady state of population: there are no changes in population

NO EVOLUTION


panmixia a model of ideally panmictic population: random mating among individuals in population; individuals

of the same generation mate together

individuals of all genotypes are equally fertile there is no selection among various genotypes

no mutations originate there is no migration the population is large enough

Equilibrium in population

equilibrium is a steady state of population genetic structure of population remains unchanged (genetic structure of subsequent generations remains the same ...)

H-W equilibrium: only in the case when there are met all conditions of ideally panmictic population (thus, no selection acts on individuals, ...)

any kind of selection some other equilibrium may be established in population new equilibrium is established if selection remains the same

through subsequent generations (the same intensity, the same preference of particular phenotypes, ...)

changes in selection changes in population equilibrium balanced polymorphism: special type of equilibrium

in population (see later)

Factors disturbing Hardy-Weinberg equilibrium

non-random mating selection acting on particular phenotypes migration occurs (immigration / emigration) new mutations originate population is small genetic drift

(bottleneck effect, founder effect)

changes in allele frequencies

Factors disturbing Hardy-Weinberg equilibrium non-random mating

assortative mating the choice of a partner because the partner possesses some

particular trait (traits) usually positive effect some genetic disorders: negative effect (people suffering

from some disorder tend to choose a partner with similar medical problems)

stratification stratified population contains a number of subpopulations that are

genetically isolated one from another e.g.: U.S. population is stratified:

2 major subpopulations (Caucasians & African Americans) other subpopulations: Native Americans, Asians, Hispanics

there is strong mating preference: partner is usually chosen inside particular subpopulation

Factors disturbing Hardy-Weinberg equilibrium selection acting on particular phenotypes

selection acts directly on phenotypes !!! through successful phenotypes, particular alleles are

transmitted into offspring individuals of various phenotypes can have different fitness:

various ability to survive various number of children fitness of particular phenotypes can vary from 0 to 1:

0 no child of particular phenotype survive to reproductive age 1 all children of particular phenotype survive to reproductive age

coefficient of selection: s = 1 - f


selection against unfavourable dominant allele this allele is expressed in each individual selection acts on all individuals who have the allele

selection against unfavourable recessive allele this allele is expressed only in homozygotes the allele is not seen in phenotype in heterozygotes

selection do not act on heterozygotes

selection can not work against alleles causing diseases with late onset


balanced polymorphism (heterozygote advantage)

AS AS

AS

AS

AS

AS AS

AS

AS

AS

AS

AS

SS AA

AA

AA

AA SS

SS

SS

AA

AA

SS

SS

p2 = 0,25 q2 = 0,25 2pq = 0,50

frequency of allele S matches to frequency of genotype SS

ZYGOTES:



AS AS

AS

AS

AS

AS AS

AS

AS

AS

AS

AS

SS AA

AA

AA

AA SS

SS

SS

AA

AA

SS

SS

p2 = 0,25 q2 = 0,25 2pq = 0,50

frequency of allele S matches to frequency of genotype SS

children:

malaria sickle-cell

disease



Selection for heterozygotes (heterozygous advantage): in certain conditions, deleterious allele S is selectively maintained in heterozygotes & the same allele S is selectively eliminated in homozygotes.

AS AS

AS

AS

AS

AS AS

AS

AS

AS

AS

AS

children:

AA

AA

AA SS

SS SS

p2 = 0,17 2pq = 0,67 q2 = 0,17



p2 = 0,17 2pq = 0,67 q2 = 0,17

AS AS

AS

AS

AS

AS AS

AS

AS

AS

AS

AS

AA

AA

but: p=0,5 q=0,5 allele frequency

genotype frequency

AA SS

SS SS


any change in selection factors fitness of particular phenotypes may be changed:

e.g.: allele HbS is frequent in human population occupying certain malaric area; heterozygotes (genotype HbA HbS) are preferred by selection

mosquitoes (vectors of malaria disease) do not live there any more

swamps were dried out

allele HbS lose its advantage for heterozygotes heterozygotes (HbA HbS) lose the advantage HbA HbA individuals have the highest fitness frequency of allele HbS decreases in population


selection factors

differentiated fitness & reproduction ability of individuals with

different phenotypes

adaptive change of genetic structure

of population

optimalization of phenotypes

evolution

Factors disturbing Hardy-Weinberg equilibrium migration

immigration emigration

migration introduction of new alleles into population e.g.: mutant alleles causing phenylketonuria (PKU):

the most common mutations are of Celtic origin migration of the Celts spreading of alleles into other

populations frequency of these alleles over the world reflects migration of

Celts incidence of PKU:

Ireland: approx. 1/4500 (lower frequency in Southern Europe)

gene flow

Factors disturbing Hardy-Weinberg equilibrium mutations

new mutations originate new alleles originate

e.g.: -thalassemia:

mutations in -globin gene are responsible for the disease there are known numerous different alleles causing

-thalassemia in different region, different mutations originated ...

Factors disturbing Hardy-Weinberg equilibrium population is small

genetic drift: fluctuation in allele & genotype frequencies from generation

to generation due to incomplete transmission of particular alleles from generation to generation (alleles are transmitted proportionally only in the case of large population ... law of statistics)

less frequent allele can be lost from population

bottleneck effect founder effect


genetic drift bottleneck effect

AA

aa

aa

aa

aa

aa

aa

AA

AA AA

aa

aa

Aa

Aa

Aa

Aa

Aa aa

Aa

Aa

Aa

Aa

Aa

aa

Aa

Aa

Aa

Aa

Aa

aa

Aa

Aa

Aa

Aa

Aa aa

Aa Aa

aa

Aa

Aa

Aa Aa

aa

Aa

Aa

Aa

Aa

Aa

Aa

Aa Aa

Aa

Aa

Aa Aa

aa aa


genetic drift bottleneck effect

aa AA

AA

Aa

Aa Aa

Aa

Aa Aa

Aa

Aa

Aa

Aa

Aa

Aa

Aa

Aa


genetic drift founder effect

AA

Aa AA

AA

AA

AA

AA

AA AA

AA

AA

AA AA AA

AA

AA AA

AA

AA

AA

AA

Aa

AA

AA

AA

AA

AA AA

AA

AA

AA AA

AA

AA

AA AA

AA

AA

AA

AA

AA

AA AA

AA AA AA

AA

AA

AA

AA

AA

AA

AA AA

AA

AA

AA

AA



AA

AA AA

AA

AA

AA AA

AA

AA

AA AA AA

AA

AA AA AA

AA

AA

Aa

AA

AA

AA

AA

AA AA

AA

AA

AA AA

AA

AA

AA AA

AA

AA

AA

AA

AA AA

AA AA AA

AA

AA

AA

AA

AA

AA

AA AA

AA

AA

AA

Aa AA

AA

AA AA



e.g.: European settlers in North America, South Africa ...

AA

AA AA

AA

AA

AA AA

AA

AA

AA AA AA

AA

AA AA AA

AA

AA

Aa

AA

AA

AA

AA

AA AA

AA

AA

AA AA

AA

AA

AA AA

AA

AA

AA

AA

AA AA

AA AA AA

AA

AA

AA

AA

AA

AA

AA AA

AA

AA

AA

Aa AA

Aa

AA aa

AA Aa

Aa

Aa AA

AA

Aa

AA

AA

AA

aa Aa

AA AA

AA

AA AA

AA AA

AA

AA


genetic drift founder effect Old Order Amish:

a religious isolate of European descent that settled in Pennsylvania

immigrants gave rise to a number of small, genetically isolated subpopulations throughout USA & Canada

the Amish tend to have large families (even single carrier present in community can transmit particular allele into a large number of children)

they marry Amish community members only genetically isolated subpopulations (with frequent consanguineous marriages)

there is relatively high incidence of specific rare AR syndromes (e.g. Ellis-van Creveld s.) in some Amish communities, but not in others


genetic drift founder effect Afrikaner subpopulation of South Africa:

in the middle of 17th century, 20 couples (mainly from Netherlands) settled there

explosive growth of population (population was genetically isolated from major population)

today, nearly 1 million of 2.5 million Afrikaners are descends of original 20 couples

1 early settler carried rare allele for variegate porphyria (AD disorder of late onset)

today's incidence of the disorder: South Africa: approx. 1/333 Netherlands: --- Finland: approx. 1/100 000

Population studies in human

population studies are important part of human genetics there are medical data records about huge number

of people they are important for genetic counselling: they

provide allele frequencies for risk calculations, ... in human, population studies are also focused on genetic

structure of human subpopulations & the flow of genes among populations and between generations

Genetic diversity in human populations

current studies suggest that human ancestors arose in Africa early humans spread out all over the world:

geographical isolation of small groups in new living conditions ( genetic isolation)

various selection factors in various regions genetic drift large human populations arose from small,

scattered original groups various new mutations in new regions

main ethnic groups evolved which include many other ethnic subgroups (they have their own characteristic sets of gene frequencies)

Genetic diversity in human populations

medical importance: there can be huge differences among subpopulations sharing common area when considering e.g. genetic disorders, etc.

Population geneticsPopulation geneticsSexual reproduction and genetic structure of population Snmek slo 4Snmek slo 5Snmek slo 6Sexual reproduction and genetic structure of populationSexual reproduction and genetic structure of populationSexual reproduction and genetic structure of populationGenetic structure of populationGenetic structure of populationGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceGenetic structure of population autosomal inheritanceHardy-Weinberg lawHardy-Weinberg law: Genotype frequenciesHardy-Weinberg lawHardy-Weinberg lawHardy-Weinberg lawH.-W. law: consequencesH.-W. law: consequencesSimplification of H.-W. lawH.-W. law: Gonosomal genes in populationH.-W. law: Gonosomal genes in populationH.-W. law: Gonosomal genes in populationHardy-Weinberg equilibriumSexual reproduction and genetic structure of populationEquilibrium in populationFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumFactors disturbing Hardy-Weinberg equilibriumPopulation studies in humanGenetic diversity in human populationsGenetic diversity in human populations

VAB11 06a Population Genetics

Documents

Transcript of VAB11 06a Population Genetics