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Hardy-Weinberg principle_Birhan Kassa.pptx

This document discusses the Hardy-Weinberg principle of population genetics. It explains that under conditions of no evolution, allele and genotype frequencies will remain constant from generation to generation. It describes how deviations from Hardy-Weinberg equilibrium occur due to evolutionary mechanisms like genetic drift, selection, mutation, and migration. The document provides examples of how to calculate allele frequencies and test for deviations from Hardy-Weinberg expectations.

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3/23/2023 1 Course Title: Population Genetics and Genetic Diversity of Farm Animals (AnGB7012) Chapter 2: Hardy-Weinberg principle Birhan Kassa: BDU1500178 Bahir Dar University, Bahir Dar
2. Hardy-Weinberg principle 2.1. The Hardy-Weinberg principle 2.2. Heterozygosity and homozygosity 23. Deviations from The Hardy-Weinberg expectations 2.4. Sex and the Hardy-Weinberg principle 3/23/2023 2
2.1. The Hardy-Weinberg principle Hardy-weinberg principle states that a populations allele and genotype frequency will remain constant in the absence of evolutionary mechanisms Ultimately, the Hardy-weinberg principle model is a population without evolution under the following conditions No mutation No immigration/emigration No natural sexual selection A large population 3/23/2023 3
If a population is not in Hardy-Weinberg equilibrium, it can be concluded that the population is evolving Evolutionary Mechanisms (will put population out of HW Equilibrium): Genetic Drift Selection Mutation Migration 3/23/2023 4
The Hardy Weinberg Theorem deals with Mendelian genetics in the context of populations of diploid, sexually reproducing individuals in given set of assumptions 1. Allele frequencies in a population will not change from generation to generation. 2. If the allele frequencies in a population with two alleles at a locus are p and q, then the expected genotype frequencies are p2 , 2pq, and q2 . This frequency distribution will not change from generation to generation once a population is in Hardy- Weinberg equilibrium. 3/23/2023 5
If the frequency of allele A in the population is p and the frequency of allele a in the population is q, Then the frequency of genotype AA = p2 The frequency of genotype Aa = 2pq The frequency of genotype aa = q2 p + q= 1 For a diploid organism (2 chromosomes), (p + q) 2 = 1 = p2 + 2pq + q2 3/23/2023 6
Hardy-Weinberg Hardy-Weinberg Equilibrium Single locus with two alleles (A and a) Fr(A) = p Fr(a) = q p + q = 1 If assumptions of Hardy-Weinberg hold, then we can predict the genotype freq’s in next generation Fr(AA) = p2 Fr(aa) = q2 Fr (Aa) = 2pq p2 + q2 + 2pq = 1 Allele freq.’s in next generation Fr(A)’ = p’ = [2(Fr(AA)) + 1(Fr(Aa))]/Total 3/23/2023 7
3/23/2023 8 Total number = 15, frequency of AA = 8/15 (0.53) Aa = 4/15 (0.27) aa = 3/15 (0.20)
Ex: Genetic structure of first generation Expected Genotype F(AA): p x p = p2 = 0.8 x 0.8 = 0.64 F(Aa): p x q + q x p = 2pq = 2 x (0.8 x 0.2) = 0.32 F(aa): q x q = q2 = 0.2 x 0.2 = 0.04 p2 + 2pq + q2 = 0.64 + 0.32 + 0.04 = 1 Allele Frequencies F (A)= p = 0.8 F (a) = q = 0.2 p + q = 1 3/23/2023 9
Expected Allele Frequency at second Generation p = AA + Aa/2 = 0.64 + (0.32/2) = 0.8 q = aa + Aa/2 = 0.04 + (0.32/2) = 0.2 3/23/2023 10
Calculating Allele Frequencies from number of Individuals Genotypes AA Aa aa # of individuals 120 60 35 #A = (2 x AA) + Aa = 240 + 60 = 300 #a = (2 x aa) + Aa = 70 + 60 = 130  Proportion A = 300/total = 300/430 = 0.70  Proportion a = 130/total = 130/430 = 0.30  A + a = 0.70 + 0.30 = 1  Proportion AA = 120/215 = 0.56  Proportion Aa = 60/215 = 0.28  Proportion aa = 35/215 = 0.16  AA + Aa + aa = 0.56 + 0.28 +0.16 = 1 3/23/2023 11
Example: estimate frequency of a disease allele in a population  Phenylketonuria (PKU) is a metabolic disorder that results from homozygosity for a recessive allele  Individuals that are homozygous for the deleterious recessive allele cannot break down phenylalanine, results in build up  à mental retardation  The occurrence of PKU is 1 per 10,000 births  How many carriers of this disease in the population? 3/23/2023 12
Rare deleterious recessives often remain in a population because they are hidden in the heterozygous state (the “carriers”) Natural selection can only act on the homozygous individuals where the phenotype is exposed (individuals who show symptoms of PKU) We can assume HW equilibrium if: There is no migration from a population with different allele frequency Random mating No genetic drift 3/23/2023 13
So, let’s calculate HW frequencies The occurrence of PKU is 1 per 10,000 births (frequency of the disease allele): q2 = 0.0001 q = sqrt(q2 ) = sqrt(0.0001) = 0.01 The frequency of wildtype (normal) alleles is: p = 1 – q = 1 – 0.01 = 0.99 The frequency of carriers (heterozygotes) of the deleterious allele is: 2pq = 2 x 0.99 x 0.01 = 0.0198 or approximately 2% of the U.S. population 3/23/2023 14
2.2. Heterozygosity and homozygosity Homozygosity is the condition of having two identical alleles at the same locus (AA, aa) and Homozygous: of an organism in which both copies of a given gene have the same allele. Heterozygous: of an organism which has two different alleles of a given gene. In Heterozygous, the only allele that is expressed is the dominant trait. The recessive is present, but its expression is hidden. Heterozygosity is of major interest to breeders of genetic variation in natural populations High heterozygosity means lots of genetic variability. Low heterozygosity means little genetic variability. 3/23/2023 15
Recessive: able to be covered by a dominant trait. Dominant: a relation ship between alleles of gene, in which one allele masks the expression of another gene with the same locus. 3/23/2023 16
Often, we will compare the observed level of heterozygosity to what we expect under Hardy- Weinberg equilibrium (HWE) If the observed heterozygosity is lower than expected, we seek to attribute the discrepancy to forces such as inbreeding If heterozygosity is higher than expected, we might suspect an isolate-breaking effect (the mixing of two previously isolated populations) 3/23/2023 17
DEVIATION from Hardy-Weinberg Equilibrium Indicates that EVOLUTION is happening 2.3. Deviations from The Hardy-Weinberg expectations 3/23/2023 18
Violations of the Hardy–Weinberg assumptions can cause deviations from expectation. How this affects the population depends on the assumptions that are violated deviation from the Hardy-Weinberg equilibrium denotes the evolution of a species Random mating: The HWP states the population will have the given genotypic frequencies (called Hardy-Weinberg proportions) after a single generation of random mating within the population. When violations of this provision occur, the population will not have Hardy-Weinberg proportions. 3/23/2023 19
Three such violations are: Inbreeding, which causes an increase in homozygosity for all genes Assortative mating, which causes an increase in homozygosity only for those genes involved in the trait that is assortatively mated (and genes in linkage disequilibrium with them) Small population size, which causes a random change in genotypic frequencies, particularly if the population is very small 3/23/2023 20
Selection: In general, causes allele frequencies to change, often quite rapidly, while directional selection eventually leads to the loss of all alleles except the favored one, some forms of selection, such as balancing selection, lead to equilibrium without loss of alleles. Mutation: Mutation will have a very subtle effect on allele frequencies. Mutation rates are of the order 10−4 to 10−8, and the change in allele frequency will be, at most, the same order. Migration: Migration genetically links two or more populations together. In general, allele frequencies will become more homogeneous among the populations. 3/23/2023 21
A X2 goodness-of-fit test can be used to determine if a population is significantly different from the expectations of Hardy-Weinberg equilibrium If we have a series of genotype counts from a population, then we can compare these counts to the ones predicted by the Hardy-Weinberg model O = observed counts, E = expected counts, sum across genotypes 3/23/2023 22 Testing for Deviation from Hardy-Weinberg Expectations
Genotype No. AA 260 Aa 180 aa 360 Example: Testing for HWE Step 1: Calculate observed allele frequency Fr(100) = (2*260 + 1*360)/(2*800) = 0.55 (= p) Fr(125) = (2*180 + 1*360)/(2*800) = 0.45 (= q 3/23/2023 23
Genotype No. Expected AA 260 p2*N=242 aa 180 q2*N=162 Aa 360 2*p*q*N=396 Step 2: Calculate expected genotype number Testing for HWE 3/23/2023 24
Genotype Observed Expected Stat AA 260 242 1.34 aa 180 162 2.00 Aa 360 396 3.27 Step 3: Compare observe to expected X2 = Σ (O-E)2/E=6.61 df = 1 crit = 3.84 Conclusion: Population deviates from HWE fewer heterozygotes than expected 3/23/2023 25
In general, the factors that are assumed to be non- operative under HWE are hardly realised in the living systems. The living system (populations or organisms) are structured (non-random entities) and are influenced by multiple and interactive factors that operate through space and time. With the help of HW equilibrium it is possible to investigate and estimate the effect of these individual forces that change gene frequency in populations.. 3/23/2023 26
Generally change in gene frequency is affected by Natural selection: Stabilizing Disruptive Directional Genetic drift Founder effect Bottleneck effect Gene flow 3/23/2023 27
Natural Selection When natural selection occurs, variation of traits in a population changes over time 3 patterns of changes due to natural selection Stabilizing Disruptive Directional 3/23/2023 28
1. Stabilizing selection Individuals with average forms of a trait has the highest fitness and the extreme values have lower fitness 3/23/2023 29
2. Disruptive selection Selection where both extreme traits are considered more fit for the environment than the intermediate trait 3/23/2023 30
3. Directional selection Individuals in a population with one extreme trait have higher fitness than the average trait 3/23/2023 31
Example 3/23/2023 32
Genetic drift Causes deviation from equilibrium Genetic drift change in agene pool due to enhance The smaller the population, the greater the impact it has on the population oFounder effect oBottleneck effect 3/23/2023 33
Founder effect 3/23/2023 34
Bottleneck effect 3/23/2023 35
Gene flow Gaining or losing when individuals move into or out of population Immigration: introduce genetic variation in to a population Emigration: reduce introduce genetic variation in to a population 3/23/2023 36
Mutation A mutation is a change in an organism’s DNA. A new mutation that is transmitted in gametes can immediately change the gene pool of a population by substituting the mutated allele for the older allele. For any single locus, mutation alone does not have much quantitative effect on a large population in a single generation. An individual mutant allele may have greater impacts later through increases in its relative frequencies as a result of natural selection or genetic drift. 3/23/2023 37
While mutations at an individual locus is a rare event, the cumulative impact of mutations at all loci can be significant. – Each individuals has thousands of genes, any one of which could experience a mutation. – Populations are composed of thousands or millions of individuals that may have experienced mutations. Over the long term, mutation is very important to evolution because it is the original source of genetic variation that serves as the raw material for natural selection.
The variation among individuals in a population is a combination of inheritable and non-heritable traits. Phenotype, the observable characteristics of an organism, is the cumulative product of an inherited genotype and a multitude of environmental influences. For example, these butterflies are genetically identical at the loci for coloration, but they emerge at different seasons. Only the genetic component of variation can have evolutionary consequences as a result of natural selection. – This is because only inheritable traits pass from generation to generation. 1. Genetic variation occurs within and between populations
Both quantitative and discrete characters contribute to variation within a population. Quantitative characters are those that vary along a continuum within a population. – For example, plant height in our wildflower population includes short and tall plants and everything in between. – Quantitative variation is usually due to polygenic inheritance in which the additive effects of two or more genes influence a single phenotypic character. Discrete characters, such as flower color, are usually determined by a single locus with different alleles with distinct impacts on the phenotype.
Polymorphism occurs when two or more discrete characters are present and noticeable in a population. The contrasting forms are called morphs, as in the red- flowered and white-flowered morphs in our wildflower population or the butterflies in the previous slide Human populations are polymorphic for a variety of physical (e.g., freckles) and biochemical (e.g., blood types) characters. Polymorphism applies only to discrete characters, not quantitative characters, such as human height, which varies among people in a continuum.
Population geneticists measure genetic variation both at the level of whole genes and at the molecular level of DNA Gene diversity measures the average percent of gene loci that are heterozygous. In the fruit fly (Drosophila), about 86% of their 13,000 gene loci are homozygous (fixed) About 14% (1,800 genes) are heterozygous.
Nucleotide diversity measures the level of difference in nucleotide sequences (base pair differences) among individuals in a population. In fruit flies, about 1% of the bases are different between two individuals. Two individuals would differ at 1.8 million of the 180 million nucleotides in the fruit fly genome. Humans have relatively little genetic variation. Gene diversity is about 14% in humans. Nucleotide diversity is only 0.1%. • You and your neighbor have the same nucleotide at 999 out of every 1,000 nucleotide sites in your DNA.
Geographic variation results from differences in genetic structure either between populations or between subgroups of a single population that inhabit different areas. Often geographic variation results from natural selection that modifies gene frequencies in response to differences in local environmental factors. Alternatively, genetic drift can lead to chance variations among populations. Geographic variation can occur on a local scale, within a population, if the environment is patchy or if dispersal of individuals is limited, producing subpopulations.
Geographic variation in the form of graded change in a trait along a geographic axis is called a cline. Clines may reflect direct environmental effects on phenotype, but also genetic differences along the cline. For example, average size of yarrow plants (Anchillea), gradually decreases with increasing variation. Although the environment affects growth rate directly to some extent with altitude, common garden experiments have demonstrated that some of the variation has a genetic basis. Fig. 23.8
In contrast to clines, isolated populations typically demonstrate discrete differences. For example, populations of house mice were first intro- duced to the island of Madiera in the 15th century, but isolated populations developed that were separated by mountains. Some isolated populations have evolved differences in karyotypes probably through genetic drift. Fig. 23.9
New alleles originate only by mutation. Mutations are changes in the nucleotide sequence of DNA. Mutations of individual genes are rare and random. Mutations in somatic cells are lost when the individual dies. Only mutations in cell lines that produce gametes can be passed along to offspring. 2. Mutation and sexual recombination generate genetic variation
Most point mutations, those affecting a single base of DNA, are probably harmless. – Most eukaryotic DNA does not code for proteins and mutations in these areas are likely to have little impact on phenotype. – Even mutations in genes that code for proteins may lead to little effect because of redundancy in the genetic code. – However, some single point mutations can have a significant impact on phenotype. • Sickle-cell disease is caused by a single point mutation.
Mutations that alter the structure of a protein enough to impact its function are more likely to be harmful than beneficial. – A random change is unlikely to improve a genome that is the product of thousands of generations of selection. – Rarely, a mutant allele may enable an organism to fit its environment better and increase reproductive success. – This is especially likely if the environment is changing – These mutations may be beneficial now. • For example, mutations that enable HIV to resist antiviral drugs are selected against under normal conditions, but are favorable under drug treatment.
Chromosomal mutations, including rearrangements of chromosomes, affect many genes and are likely to disrupt proper development of an organism. – However, occasionally, these dislocations link genes together such that the phenotype is improved. Duplications of chromosome segments, whole chromosomes, or sets of chromosomes are nearly always harmful. – However, when they are not harmful, the duplicates provide an expanded genome. – These extra genes can now mutate to take on new functions.
Because microorganisms have very short generation times, mutation generates genetic variation rapidly. – In an AIDS patient, HIV generates 1010 new viruses per day. – With its RNA genome, mutation rate is higher than DNA genomes. – This combination of mutation and replication rate will generate mutations in the HIV population at every site in the HIV genome every day. • In the face of this high mutation rate, single-drug treatments are unlikely to be effective for very long and the most effective treatments are multiple drug “cocktails.” –It is far less probable that mutations against all the drugs will appear in individual viruses in a short time.
In organisms with sexual reproduction, most of the genetic differences among individuals are due to unique recombinations of the existing alleles from the population gene pool. – The ultimate origin of allelic variation is past mutations. Random segregation of homologous chromosomes and random union of gametes creates a unique assortment of alleles in each individual. Sexual reproduction recombines old alleles into fresh assortments every generation.
The tendency for natural selection to reduce variation is countered by mechanisms that preserve or restore variation, including diploidy and balanced polymorphisms. Diploidy in eukaryotes prevents the elimination of recessive alleles via selection because they do not impact the phenotype in heterozygotes. – Even recessive alleles that are unfavorable can persist in a population through their propagation by heterozygous individuals. – Recessive alleles are only exposed to selection when two parents carry the same recessive allele and these are combined in one zygote. – This happens only rarely when the frequency of the recessive allele is very low. – Heterozygote protection maintains a huge pool of alleles that may not be suitable under the present conditions but that could be beneficial when the environment changes. 3. Diploid and balanced polymorphism preserve variation
Balanced polymorphism maintains genetic diversity in a population via natural selection. One mechanism in balance polymorphism is heterozygote advantage. – In some situations individuals that are heterozygous at a particular locus have greater survivorship and reproductive success than homozygotes. – In these cases, multiple alleles will be maintained at that locus by natural selection. Heterozygous advantage maintains genetic diversity at the human locus for one chain of hemoglobin. – A recessive allele causes sickle-cell disease in homozygous individuals. – Homozygous dominant individuals are very vulnerable to malaria. – Heterozygous individuals are resistant to malaria.
• The frequency of the sickle-cell allele is highest in areas where the malarial parasite is common. – The advantages of heterozygotes over homozygous recessive individuals who suffer sickle-cell disease and homozygous dominant individuals who suffer malaria are greatest here. – The sickle-cell allele may reach 20% of the gene pool, with 32% heterozygotes resistant to malaria and 4% with sickle-cell disease.
• A second mechanism promoting balanced polymorphisms is frequency-dependent selection. • Frequency-dependent selection occurs when the reproductive success of any one morph declines if that phenotype becomes too common in the population. – The relationships between parasites and their hosts often demonstrate this type of relationship. • Hosts often vary in their defense against parasites and parasites in their ability to infect hosts. – Those parasites that are capable of infecting the most common host type will increase in abundance. – The rarer host types will increase as the genetic frequencies in the parasite population shifts. – These shifts in genetic frequencies among hosts and among parasites maintain variation in both populations.
• Aspects of this teeter-totter of frequency- dependent selection can be seen in the host- parasite between clones of aquatic snails and a parasitic worm. – In these snails which reproduce asexually, the most common snail clones suffer the higher infection rates than the least common clone, suggesting frequency- dependent selection. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 23.11
• Some genetic variations, neutral variation, have negligible impact on reproductive success. – For example, the diversity of human fingerprints seems to confer no selective advantage to some individuals over others. – Much of the protein and DNA variation detectable by methods like electrophoresis may be neutral in their adaptive qualities. • The relative frequencies of neutral variations will not be affected by natural selection. • Some neutral alleles will increase and others will decrease by the chance effects of genetic drift. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• There is no consensus on how much genetic variation can be classified as neutral or even if any variation can be considered truly neutral. – It is almost impossible to demonstrate that an allele brings no benefit at all to an organism. – Also, variation may be neutral in one environment but not in another. – Even if only a fraction of the extensive variation in a gene pool significantly affects an organism, there is still an enormous reservoir of raw material for natural selection and adaptive evolution. KSJ : This is typical selectionist phrases! The opposite could be said for all points above. In short, most mutations will have a negative effect on the organism. Survival of a mutation (i.e. Allele is thus coupled to neutral or near-neutral properties.
Migration: A population could out of HWE with a lot of migration 3/23/2023 60
Example 3/23/2023 61
3/23/2023 62
3/23/2023 63 • Mutation • Changes to an organism’s DNA • Most common way to introduce novel genotypic and phenotypic variance. • Some are unfavorable or harmful and are quickly eliminated from the population by natural selection. • Some are beneficial and will spread • Some do not do anything and can linger, unaffected by natural selection
• Nonrandom mating 1. Mate choice • Natural selection picks traits that lead to more mating for an individual • Assortative mating = individual’s preference to mate with partners who look the same 2. Physical location • In large populations spread over vast geographic distances, not all individuals will have equal access to one another 3/23/2023 64
• Environmental variance • Human skin color • Temperature-dependent sex determination in reptiles • Geographical variation in environmental conditions • Can produce clines • Phenotype of a species' populations varies gradually across an ecological gradient (ie. Bergmann’s Rule) 3/23/2023 65
2.4. Sex and the Hardy-Weinberg principle Where the A gene is sex-linked The heterogametic sex (e.g., mammalian males; avian females) have only one copy of the gene (and are termed hemizygous), The homogametic sex (e.g., human females) have two copies. The genotype frequencies at equilibrium are p and q for the heterogametic sex but p2, 2pq and q2 for the homogametic sex. 3/23/2023 66
For example, in humans red-green colorblindness is an X-linked recessive trait. In western European males, the trait affects about 1 in 12, (q = 0.083) whereas it affects about 1 in 200 females (0.005, compared to q2 = 0.0070), very close to Hardy- Weinberg proportions. If a population is brought together with males and females with different allele frequencies, the allele frequency of the male population follows that of the female population because each receives its X chromosome from its mother. The population converges on equilibrium very quickly. 3/23/2023 67
3/23/2023 68 If allele frequencies differ between the sexes, it takes two generations of random mating to attain Hardy-Weinberg equilibrium. Sex-linked loci require multiple generations to attain equilibrium because one sex has two copies of the gene and the other sex has only one.
Consider a sex-linked locus in a species where females are XX (homogametic) and males are XY (heterogametic). Suppose f(a) is initially unequal in females and males. (1) Because each female receives an X chromosome from both parents in generation n, the female f(a) in generation n+1 is the mean of the male and female f(a) in generation n. (2) Because each male in receives an X chromosome only from the female parent in generation n, the frequency of the allele f(a) in females of generation n automatically determines f(a) in males in generation n+1. The male f(a) therefore "chases" the female f(a) in the preceding generation until they reach approximate equality. In this example, note that frequencies are within 1% of each other in the seventh generation, even when the initial frequencies are completely divergent. Note that, because females contribute two X chromosomes each and males one X each, the mean f(a) for a sex-linked locus is a constant (2 x f(a) + 1 x f(a)) / 3 . In this case, (2x1 + 1x0) = 0.6667 and remains constant. 3/23/2023 69