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GENETICA DELLE GENETICA DELLE POPOLAZIONIPOPOLAZIONI

Alberto PallaviciniAlberto Pallavicini

Allele Frequencies in Population Gene Pools Vary in Space and Time

• A population is a group of individuals with a common set of genes that lives in the same geographic area and can or does interbreed.

• A population's gene pool is all of the alleles present in that population. Due to population dynamics, the gene pool can change over time.

The Hardy-Weinberg Law Describes the Relationship between Allele Frequencies and Genotype Frequencies in an Ideal Population

• The Hardy-Weinberg law makes two predictions:

(1) the frequency of the alleles in the gene pool does not change over time; and

(2) after one generation of random mating, the genotype frequencies for two alleles can be calculated as

p2 + 2pq + q2 = 1

where p equals the frequency of allele A and q is the frequency of allele a

• The Hardy-Weinberg model assumes that there is – no selection,– no new alleles arise from mutation, – no migration into or out of the

population, – the population is infinitely large, – random mating occurs.

The Hardy-Weinberg Law Can Be Applied to Human Populations

• An example of how the Hardy-Weinberg law can be applied to humans is analysis of susceptibility to HIV-1 infection based on the genotype for the CCR5 HIV-1 receptor gene.

Verifica dell’equilibrio di H-W

Per la verifica dello stato di equilibrio il test statistico da utilizzare e quello del χ2 (chi-chi-quadro).).

In una popolazione di 150 mosche

• 15 hanno gli occhi rossi

• 90 hanno gli occhi di colore normale

• 45 hanno gli occhi rosa

Questa popolazione è in equilibro di HW?

Verifica dell’equilibrio di H-W

1° passo: Determinare le frequenze alleliche della generazione corrente

Verifica dell’equilibrio di H-W

Verifica dell’equilibrio di H-W

2° passo: Determinare le frequenze genotipiche attese nella prossima generazione

• p2= f (chi-R) f (chi- R)=0.5625∗ f ( R)=0.5625

• q2= f (chi-r) f (chi-r)=0.0625∗ f ( R)=0.5625

• 2 pq=2 [ f (chi-R) f (chi-r)]=0.375∗ f ( R)=0.5625 ∗ f ( R)=0.5625• 84 mosche con occhi normali (RR)• 9 mosche con occhi rossi (rr)• 56 mosche con occhi rosa (Rr)

3° passo: Si confronta la frequenza attesa con i numeri originali della popolazione

Verifica dell’equilibrio di H-W

Gradi di libertà della distribuzio).ne=(chi- Numero). delle classi−1)−numero). di parametri stimati

Poichè abbiamo 3 genotipi, avremo

no). gradi di libertà=(chi-3−1)−1=1

Se consideriamo un livello di significatività pari al 5%, ovvero α = 0.05, otteniamo il valore critico

X2 0.05 =3.84

Verifica dell’equilibrio di H-W

The Hardy-Weinberg Law Can Be Used for Multiple Alleles, X-Linked Traits, and Estimating Heterozygote Frequencies

• Frequencies for multiple alleles can be calculated using the Hardy-Weinberg equation by adding more variables…

• For instance, in a situation involving three alleles

(p + q + r = 1),

the frequencies of the genotypes are given by

(p + q + r)2 = p2 + q2 + r2 + 2pq + 2pr + 2qr = 1.

• An example of genotype frequency calculations for ABO blood type .

• In using the Hardy-Weinberg equation to calculate allele and genotype frequencies for X-linked traits in mammals, the frequency of the X-linked allele in the gene pool will equal the frequency of males expressing the X-linked trait.

• For females, the frequency of having the allele in question will be q2 if the allele frequency is q.

– Daltonismo 8% nei maschi– Quale è la frequenza delle femmine

daltoniche? E di quelle portatrici?

• The Hardy-Weinberg law also allows the frequency of heterozygotes in a population to be estimated. In general, the frequencies of all three genotypes can be estimated once the frequency of either allele is known and Hardy-Weinberg assumptions are invoked.

ESERCIZIO

Per il locus PCI, nella popolazione di Daphnia dei bacino di Ojibway, Spitz trovò due alleli, S e S-, e determinò che il numero di individui di ciascun genotipo era 42 SS, 48 SS- e 38 S-S-. Verifica se i genotipi mostrano deviazione dall'HWE.

Natural Selection Is a Major Force Driving Allele Frequency Change

• If individuals of all genotypes are subject to natural selection and do not have equal rates of survival and reproductive success, allele frequencies may change from one generation to the next. •Natural selection is the principal force that shifts allele frequencies within large populations.

• Hardy-Weinberg analysis allows fitness w to be examined for each genotype.

• For a homozygous recessive individual that dies before producing offspring,

w = 0,

and the frequency of the recessive allele will decrease in each generation.

Calcolo della fitness

• qg=q

0/(1+gq

0)

a1a1 a1a2 a2a2

W 1 1 1 - s

genot. po2 2poqo qo

2

Gametes po2 2poqo qo

2(1-s)

Total gametes 1-sqo2

q1=q

0(1-sq0)/(1-sq0

2)

• The rate at which the frequency of a deleterious allele declines depends on the strength of selection applied.

• CCR5-D32

1/1 0.81 1/D32 0.18 D32/D32 0.01

1% della popolazione muore di AIDS

• quante generazioni

per arrivare a

0,11?

Selezione a favore dell’eterozigote

Fitness media:

Si otterrà un equilibrio quando:

Polimorfismo bilanciato

• Selection in natural populations works as predicted to increase the frequency of the allele to which selective pressure is applied.

• No such increase is observed in populations not subjected to the selection.

• Selection acting on quantitative traits can be– directional,– stabilizing, or– disruptive.

• In directional selection, the genotype conferring one phenotypic extreme is selected, resulting in a change in the population mean over time.

One of the classic studies in the evolution of natural populations was conducted by Rosemary and Peter Grant and coworkers on Darwin's finches. It is among the first–and is certainly the most elegant–study to document evolution in a wild population of vertebrates. Rosemary and Peter investigated Darwin's finches for almost 3 decades and conducted most of their field work on two small islands, Daphne Major and Genovesa, in the Galápagos archipelago, Ecuador.

• In stabilizing selection, intermediate types are favored, and both extreme phenotypes are selected against. This will reduce the population variance over time but not the mean.

• In disruptive selection (divergente), both phenotypic extremes are selected for, and the intermediates are selected against. This will result in a population with an increasingly bimodal distribution for the trait.

• Mutation is the only process that creates new alleles in a gene pool.

Because most mutations are recessive, indirect methods using probability and statistics are often employed to determine the mutation rate.

Mutation Creates New Alleles in a Gene Pool

• If the mutation rate is known, the extent to which mutation can cause allele frequencies to change from one generation to the next can be estimated.

• In general, although mutation provides the raw material for evolution, mutation by itself plays a relatively insignificant role in changing allele frequencies.

• CFTR locus

• 2% in European population

• W very low

• Positive selection for heterozygotes?

• When a species divides into populations that are separated geographically, the allele frequencies in these new populations may differ over time due to migration.

Migration and Gene Flow Can Alter Allele Frequencies

• Migration occurs when individuals move between the populations and may have a large effect on allele frequency if– the rate of migration is large or– if the allele frequency of the migrant

population differs greatly from that of the population to which it is moving.

• P'i=(chi-1-m)p

m + mp

i

Genetic Drift Causes Random Changes in Allele Frequency in Small Populations

• Genetic drift occurs when the number of reproducing individuals in a population is too small to ensure that all the alleles in the gene pool will be passed on to the next generation in their existing frequencies.

• Genetic drift may result in one allele becoming fixed and one allele disappearing in a population.

Nonrandom Mating Changes Genotype Frequency but Not Allele Frequency

• Nonrandom mating can take the form of positive assortive mating in which similar genotypes are more likely to mate than dissimilar ones, negative assortive mating in which dissimilar genotypes are more likely to mate than similar ones, and inbreeding in which mating individuals are related.

• For a given allele, inbreeding increases the proportion of homozygotes in the population, and a completely inbred population theoretically will consist only of homozygotes.

• Self-fertilization is a form of inbreeding common in plants. The rate of homozygotes in a self-fertilizing population rapidly increases over a few generations, but the overall allele frequency does not change.

• A coefficient of inbreeding can be calculated to give the probability that two alleles of a given gene in an individual are identical because they are descended from the same single copy of the allele in an ancestor.

Accoppiamento consanguineo

Incrocio tra parenti prossimi inincrocio

Molto usato in agricoltura e nell’allevamento degli animali per ottenere individui con particolari caratteristiche

Nell’uomo motivi sociali e culturali riducono, ma non eliminano del tutto, l’incidenza del matrimonio tra consanguinei

I matrimoni consentiti sono quelli tra primi cugini, tra secondi cugini e tra zio/a e nipote

• One consequence of inbreeding is an increased chance that an individual will be homozygous for a recessive deleterious allele. The significance of this fact is that inbred populations often have a lowered mean fitness, called inbreeding depression.

Hai campionato una popolazione della quale sai che la percentuale degli omozigoti recessivi per il gene “a” (aa) è del 36%. Usando questo dato calcolare:

La frequenza dei genotipi “aa”

La frequenza dell’allele “a”

La frequenza dell’allele “A”

Le frequenze dei genotipi “AA” “Aa”

Le frequenze dei due possibili fenotipi con “A” completamente dominante su “a”