BMSc 241 section 2
What did R. A. Fisher (1890-1962), J. B. S. Haldane (1892-1964) and S. Wright (1889-1988) do?
(all 3) examined the theoretical consequences of Mendelian inheritance in natural populations
What is the basics of population genetics?
*A fundamental principle of population genetics is the Hardy-Weinberg Equilibrium *In the absence of natural selection, mutation, migration and genetic drift, and if there is random mating, allele and genotype frequencies in a population will remain the same generation after generation. *Mutation, genetic drift and natural selection can cause isolated populations to diverge from one another. Migration retards this divergence
Case study-What are PrP Allele Frequencies in Female Foré?
*A study focused on Foré women and girls because females were the most common victims; during mortuary feasts females ate the internal organs (including neural tissue) of their deceased kin, and when men joined in they tended to just eat muscles, and so fewer of them got sick *First the research determined the allele frequencies of the PrP gene among 140 Foré females who were too young to have practised ritual cannibalism and who were thus never exposed to kuru *(Testing for HW Proportions)-The allele and genotype frequencies among these unexposed females conformed to Conclusion 2 of the Hardy-Weinberg analysis (hence, no evolution/selection) --Secondly, the same analysis was conducted on a sample of 30 older Foré women who had participated in mortuary feasts, but had never contracted kuru *(HW: Older, Exposed Fore Females)-There is a striking excess of heterozygotes, and a corresponding deficit of homozygotes among older Foré women. The most plausible explanation is that the homozygotes individuals are susceptible to kuru whereas heterozygotes are resistant (Note-Female who survived)
Case study-What is the mode of transmission of HIV?
*AIDS is primarily a disease of developing countries *In developing countries heterosexual sex is the primary mode of HIV transmission
Case study: How do anti-viral drugs work?
*AZT1 is a T (thymine DNA base) with an -N3 and not an -OH group *When the reverse transcriptase adds AZT instead of T to a growing copy of HIV DNA, synthesis stops.
What is the Nature of Natural Selection?
*Acts on individuals, but its consequences occur in populations *Acts on phenotypes, but evolution consists of changes in allele frequencies *Populations, not individuals, evolve. Evolution is a "statistical change".
What the are important principles behind Hardy-Weinberg Principle?
*Allele and genotype frequencies are in equilibrium in a randomly mating population when there is no selection mutation, migration or random drift *Allele frequencies do not change in an equilibrium population, generation after generation *The Hardy-Weinberg equilibrium is our null model for alleles in a population
What is the most important idea of Allele frequencies in Hardy-Weinberg Equilibrium principle?
*Allele frequencies do not change from one generation to the next *Gene frequencies in a population do not alter from generation to generation in the absence of migration, selection, statistical fluctuation, mutation, etc
What are possible techniques for measuring Genetic Variation: Proteins and DNA sequences?
*Allozyme Variation *Protein Electophoresis *Microsatelliate DNA *Polymerase Chain Reaction (PCR) *DNA Sequencing *Gel Electrophoresis
Case study (Kuru)-What is background information about the prion protein locus (PrP)
*An individual's genotype at the PrP gene on chromosome 20 influences his or her susceptibility to spongiform diseases (e.g. variants of CJD) *There are two common alleles of the gene, which differ in the amino acid specified for position 129 of the encoded protein: Met (Methionine) vs Val (Valine) * The genotype frequencies in the Caucasian population: 39% Met/Met, 50% Met/Val, and 11% Val/Val. To date every vCJD victim in the Caucasian population has been the genotype Met/Met *Is there a similar pattern of genetic variation for resistance to kuku among the Foré?
How much genetic variation is there in natural populations?
*At first glance, it seems that members of a well-adapted population should be highly homozygous because the most favourable allele at each locus has become fixed *An examination of most populations reveals many phenotypic similarities among individuals. However, a large body of evidence indicates that most populations contain a high degree of heterozygosity. *This "built-in" genetic diversity is concealed, so to speak, because it is not necessarily apparent in the phenotype *A phenotype with no genetic variation will not respond to selection; if there is genetic variation, the phenotype will change over a few generations Dramatic example: Wild wolves --(Artifical selection)------>Domestic dogs
Case study: How can two distinct deceptive advertisements persist together in Elderflower orchid populations?
*Bumblebees tend to alternate between colours *If a bee visits a purple colour first and finds no reward, it looks next in a yellow flower *Bumblebees tend to visit equal numbers of yellow and purple flowers, orchids with the less common of the two colours receive more visits per plant *If more pollinator visits translates into higher reproductive success, then the rare colour has a reproductive advantage *Selection by bumblebees favours yellow until it becomes too common, then it favours purple
Case study: Mutation-Selection Balance effect on Spinal Muscular Atrophy?
*Characterised by weakness and wasting of the muscles that control voluntary movement *Caused by deletions in a locus called telomeric survival motor neuron gene (telSMN) located on chromosome 5 *The second most common lethal autosomal recessive disease in Caucasians after cystic fibrosis *Collectively the loss-of-function alleles of telSMN have a frequency of about 0.01 and s has been estimated at 0.9 With such strong selection, how do these alleles persist at a frequency of 1 in 100? q=square root (µ/s) -q = 0.01 and s = 0.9, then µ would be 0.9 x 10-4 mutations per telSMN allele per generation -Analysis of 340 individuals with spinal muscular atrophy later showed that 7 affected individuals carried new mutations that were not present in either parent -The estimated mutation rate for these recessive alleles is 1.1 x 10-4
Case study- What is Sickle Cell Anaemia?
*Common in West Africa and the Mediterranean *Recessive genetic disorder (ss) *Abnormal haemoglobin molecules: instead of remaining soluble in the cytoplasm, they aggregate to form long fibres that deform the red blood cell *The deformed cells (sickle shaped) clot small blood vessels and reduce O2 flow to tissues. Untreated it can be lethal *Sickle cells are fragile. White cells consume the remains *Sickle cell haemoglobin (s) is distinguished by a single amino acid substitution (GAG glutamic acid to GTG valine) from normal haemoglobin (H). -HH = normal red blood cells -Hs = a mild form of sickle cell anaemia -ss = severe anaemia (sickle cell disease) *However, if heterozygotes (Hs) are infected by the malaria causing protozoan, the cells are broken down more rapidly than "normal" homozygotes (HH). *Heterozygote advantage arises from a balance of opposing selective factors (i.e. anaemia and malaria).
What are the conclusions from the Hardy-Weinberg Principle?
*Conclusion 1: The allele frequencies in a population will not change, generation after generation. *Conclusion 2: If the allele frequencies in a population are given by p and q the genotype frequencies will be given by p^2, 2pq, and q^2.
Case study-What is Spongy Brain Disease?
*Creutzfeldt-Jakob Disease (CJD), Kuru in PNG, Scrapie in sheep, and Mad Cow Disease are all Spongiform Diseases *These are caused by rouge prion proteins (PrP) punching holes in brain tissue and the result is neurological deterioration. The tissue develops a sponge-like appearance *There are three ways an individual can end up with a prion disease: (1) Eating tissue infected with PrP-res (2) An inherited mutation in the gene that codes for PrP-sen (3) PrP-res forms spontaneously
Case study: Are the alleles that cause cystic fibrosis maintained by a balance between mutation and selection?
*Cystic fibrosis is caused by recessive loss-of-function mutations in a locus on chromosome 7 that encodes a protein called the cystic fibrosis transmembrane conductance regulator (CFTR) *CFTR is a cell surface protein expressed in the mucus membrane lining the intestines and lungs *CFTR's key function is to enable cells of the lung lining to ingest and destroy Pseudomonas bacteria *These bacteria cause chronic lung infections and lead to severe lung damage *Until recently, few affected individuals survived to reproductive age; those that do survive are often infertile The alleles that cause cystic fibrosis have a collective frequency of about 0.02 among people with European ancestry q=square root (µ/s) *If we assume s is 1.0, then µ would have to be 4 x 10-4 *But the actual mutation rate is about 6.7 x 10-7 -Therefore a steady supply of mutations can not explain the maintenance of cystic fibrosis alleles at 0.02 *Hypothesis: cystic fibrosis heterozygotes are resistant to typhoid fever *Salmonella typhi bacteria infiltrate the gut using CFTR proteins as entry points
Who were major players in Laying down the Foundations of population genetics (Evolution)?
*Darwin (1809-1882) *Mendel (1823-1884) --Both established the foundations of population genetics, although neither realised it. *G. H. Hardy and W. Weinberg in 1908 *R. A. Fisher (1890-1962), J. B. S. Haldane (1892-1964) and S. Wright (1889-1988) *T. Dobzhansky (1900-1975) *E. B. Ford, P. M. Sheppard and H. B. D.Kettlewell
What are the types of selection?
*Directional *Stabilising *Disruptive
What range of effects does Selection have?
*Eliminates genetic variation, but it can also maintain genetic variation *Changes allele frequencies, but it also can prevent allele frequencies from changing * Produces genetic divergence between population, but it can also maintain genetic uniformity Which of these effects occurs depends primarily on the relative fitness of the genotypes and on the relative frequencies of the alleles in the population *Strong selection can quickly change allele frequencies
What is random Genetic Drift?
*Genetic drift is random variation of allele frequencies from one generation to the next *In populations of finite size, chance events - in the form of sampling error in drawing gametes from the gene pool - can cause evolution *Selection is differential reproductive success that happens for a reason; genetic drift is differential reproductive success that just happens *Genetic drift is most important in small populations
What happens to Allele Frequency in a population?
*Genotypes breakdown to alleles when gametes are formed, and alleles, not genotypes, are passed from one generation to the next *Only alleles have continuity and evolution is change of allele frequencies in the gene pool
Case study: What is the Life Cycle of HIV?
*HIV's gp120 protein binds to the CD4 and CCR5 co-receptor on the host cell *Viral RNA is converted into DNA *Viral DNA is integrated into the Host's genome (retrovirus)
What is Selection of Heterozygotes?
*Heterozygote advantage: Balancing selection, Overdominance, or Heterosis *There is an equilibrium of allele frequencies when the heterozygote (Aa) has the highest fitness *Maintains genetic variation in a population (i.e. both alleles) *The most famous example is Sickle Cell Anaemia in the human population *Different populations may lose different alleles
What is Mutation-Selection Balance?
*In combination with selection, mutation becomes a potent evolutionary force *Most mutations are deleterious and selection acts to eliminate them from a population *Deleterious mutations can persist, however because they are continually created anew •When the rate of elimination by selection equals the rate at which new copies are being created by mutation, the frequency of the allele is at equilibrium
What is the advantage and disadvantage of Natural Selection?
*In most cases mutations will be deleterious and so lower fitness. These mutations will be removed fairly quickly from the population by purifying or negative selection *At other times a new mutation might have a higher fitness than all others in the population and it is able to multiple more quickly (NB. other alleles in the population are not necessarily deleterious). This is called positive selection, and will eventually lead to fixation of the selectively favoured allele in the population
What is an Example of Selection of an Genotype?
*Kuru is a fatal neurological disorder known only from an epidemic that struck the Foré people, who inhabit the remote jungle hamlets in Papua New Guinea, during the last century *The word kuru (in Foré language) means shivering or trembling; it describes the initial symptoms of the disease *Kuru is a spongy brain disease and is caused by misfolded proteins, which kill neural cells *Thousands of Foré people unwittingly gave themselves kuru by eating the bodies of relatives who had died of the disease *Foré's funeral rituals: the Foré cooked and ate their dead relatives. This practice was typically carried out by the Foré women and children, who lived apart from the men *This explains why men were rarely infected, and why cases appeared within families *At the height of of this epidemic in the late 1950's kuru was killing about 1% of the Foré population each year. Since then cannibalism has stopped and the epidemic has gradually waned *Kuru can have a long incubation time. The people who come down with kuru today are in their 50s and 60s, which means that they have been harboring the disease ever since they ate infected tissue as young children
What are models of migration?
*Mainland-island (source-sink) *Island model *Linear stepping-stone model *Two dimensional stepping-stone model *Metapopulation
What are Mircosatelliate DNA?
*Microsatellites, also known as simple sequence repeats (SSRs) or short tandem repeats (STRs), are repeating sequences of 2-5 base pairs of DNA *Microsatellites have become the most widely used DNA marker in modern population genetics *These DNA markers vary in their number of tandem repeats (i.e. size differences) *Tandem repeats of a short sequence motif of one to six nucleotides *For example:"TTTTTT" or "CACACACACA"
How is the important overall idea of Migration?
*Migration is a potent force of evolution (can effect allele frequency fast) *In practice, migration is most important in preventing populations from diverging *Gene flow between populations creates a larger single population - increases the effective population size (Ne) *The introduction of new alleles into a population from another species (hybridisation) or subspecies is called introgression
What is Migration?
*Migration, in an evolutionary sense, is the movement of alleles between populations (gene flow) *The mechanisms range from occasional long-distance dispersal of juvenile animals to the transport of pollen, seeds, or spores by wind, water, or animals *The actual amount of migration varies enormously among species, and depends on the mobility of individuals or propagules
What is Protein Electophoresis (Gel electrophoresis)?
*Protein electrophoresis is a method for analysing the proteins in a fluid or an extract. The electrophoresis may be performed with a small volume of sample in a number of alternative ways with or without a supporting medium: SDS polyacrylamide gel electrophoresis (in short: gel electrophoresis, PAGE, or SDS-electrophoresis). *Gel electrophoresis is a method for separation and analysis of macromolecules (DNA, RNA and proteins) and their fragments, based on their size and charge. larger fragments move faster than smaller fragments. (Proteins, DNA, RNA negatively charge are attracted or repelled up from the sample well through the gel)
What is Allozyme Variation?
*Proteins consist of a sequence of amino acids *Some amino acids carry a positive or negative charge. Overall the protein has a net charge, the sum of the amino acids. *Amino acid substitutions (DNA mutations) change the net charge, and hence change the rate of migration of a protein in an electric field
Case study: What are Anti-retroviral Drugs
*Reverse transcriptase inhibitors: stop RNA from being converted into DNA *Protease inhibitors: stop the processing of proteins *Fusion inhibitors: prevent the virus from entering the cell *Integrase inhibitors: block HIV inserting DNA into the host genome
What are Forces of Evolution?
*Selection *Mutation *Migration *Genetic Drift
What is Frequency-dependent selection?
*Selection can also maintain two alleles in a population if each allele is advantageous when it is rare *Example: Yellow and purple colour polymorphism exists in populations of European Elderflower orchids. They are pollinated by newly emerged naïve bumblebees, but the bees are always disappointed because these plants are rewardless; they have no nectar
What are Different patterns of Selection?
*Selection on Recessive and Dominant Alleles -Selection is most potent when it is acting on common recessive alleles (and rare dominant alleles) *Selection on Heterozygotes and Homozygotes -Selection can act to maintain two alleles at a stable equilibrium -When heterozygotes have inferior fitness, one allele tends to go to fixation while the other is lost. However, different populations may lose different alleles *Frequency-Dependent Selection -Selection can maintain two alleles in a population if each allele is advantageous when it is rare
What are Types of Mutations?
*Silent mutation (synonymous) *Replacement mutation (non-synonymous) *Nonsense mutation *Some mutations are neutral (e.g. synonymous mutations), and others can affect the function of the DNA sequence
What is DNA Sequence Variation?
*The 'bottom line' of genetic variation *Sample coding and non-coding genetic variation, and functional as well as silent changes *DNA sequence data can be used to infer genealogical trees ("tree thinking") *Two main kinds: Direct DNA sequencing and DNA length differences
Case study: The molecular clock: when did HIV enter the human population?
*The ancestor of the HIV-1 virus was dated back to 1930 *Therefore HIV-1 was not spread through a contaminated polio vaccine in the 1950s
What are some examples of Natural Selection?
*The arrival of invasive species can devastate natural ecosystems, but in some cases native organisms appear to be adapting to the presence of the invader. Strong evidence of adaptive changes (reduction in gape size and a steady increase in body length) in Australian native predators (Red bellied black snake and Common tree snake) as a result of the invasion of toxic cane toads (Bufo marinus).
Case study HIV: Why the drugs don't work?
*The reverse transcriptase is error prone, which results in genetic variation in the virus population *Some mutations in the active site of reverse transcriptase make this enzyme less likely to add AZT instead of T (i.e. phenotypic variation)
What is an example of Migration?
*The water snakes of Lake Erie, Ohio *Live on the mainland surrounding Lake Erie and on the islands in the lake *(banded form vs unbanded form frequency) *On islands snakes bask on limestone rocks at the waters edge. *Very young unbanded snakes are more cryptic than banded: vulnerable to predation *Mark-recapture studies (among others) showed unbanded snakes have higher survival rates *However, why are the islands not all unbanded *Every generation several banded snakes move from the mainland, contributing to the gene pool
What are Requirements for Natural Selection?
*There must be phenotypic variation among individuals *These variations must be heritable (at least to some degree) *These variations must cause differences in reproductive success
What use is the Hardy-Weinberg Principle?
*This is a null model for how Mendelian genes behave in a population. *The H-W model is useful because it rests on a specific set of assumptions we made about an idealised population. *By providing a set of explicit conditions under which evolution does not occur, the H-W can identify when evolution is happening in a real population.
What is Mainland-island Model (source-sink)?
*Two populations: one the mainland and the other on a small island offshore *Let us only consider gene flow in one direction (mainland to island)
How can we test whether a population is in H-W equilibrium?
*Using genotype frequencies measured in a natural population (i.e. observed genotypes) we can calculated the allele frequencies p and q. *The allele frequencies can be used to calculate the expected genotype frequencies: p^2 + 2pq + q^2 *The observed genotypes can be compared to the expected genotypes using a simple chi-square (χ2) test. Difference ≠ H-W equilibrium.
Case study: Why does HIV population evolve resistance?
*Variation due to mutation, inheritance, and differences in survival due to AZT selection, results in a change in the composition of the population over time
What does Fitness values mean of the Types of Selection?
1) w11 = w12 = w22 = 1.0 No selection 2) w11 = w12 < 1.0 and w22 = 1.0 Against the dominant allele (Directional) 3) w22 < 1.0 and w11 = w12 = 1.0 Against the recessive allele (Directional) 4) w11 < w12 < 1.0 and w22 = 1.0 Heterozygote intermediate (Directional) 5) w11 < w22 < 1.0 and w12 = 1.0 Heterozygote favoured (Stabilising) 6) w12 < w11 , w22 = 1.0 Homozygotes favoured (Disruptive) Direction depends on the initial allele frequency
Why is HIV a good example for us to study the principles of evolution?
1. Accumulates genetic variation rapidly: error prone reverse transcriptase 2. Strong selection agents: immune system and anti-viral drugs *These lead to changes in allele frequencies and the result is evolution
Case study: What else can an evolutionary analysis tell us about HIV?
1. Molecular phylogenetics: how did HIV enter the human population? 2. The molecular clock: when did HIV enter the human population? 3. Detecting human resistance: where did the alleles that protect some people come from?
What is Evolution by Natural Selection?
1. Mutation creates new alleles, and segregation and independent assortment shuffles them into new combinations. VARIATION (of Phenotypes) 2. Individuals pass their alleles on to their offspring. INHERITANCE 3. Some individuals are more successful at surviving and reproducing than others. SELECTION 4. The individuals that survive and reproduce, or who reproduce the most, are those with the alleles and allelic combinations that best adapt them to their environment. ADAPTATION
What are the assumptions of Hardy-Weinberg Equilibrium Principle?
1. There is no natural selection 2. There is no mutation 3. There is no migration 4. Infinite population size (i.e. no genetic drift) 5. Random mating
What is Hardy-Weinberg Equilibrium Principle?
Allele and genotype frequencies in a population will remain the same unless some evolutionary process is operating to change them
What is The Relationship between Genotypes and Alleles in a Population under H-W equilibrium?
An example of a population where p = 0.3 and q = 0.7 (1) Heterozygote proportions are maximal when p = q = 0.5. (2) Rare alleles are found more often in heterozygotes than in homozygotes.
How does Selection effect evolution?
Can be a major force driving allele frequency change, and leads to adaption
How does Genetic Drift effect evolution?
Causes random changes in allele frequency especially in populations
What is Evolution?
Change in Allele Frequencies over time. Change in the frequency of an allele in a population
How does Mutation effect evolution?
Creates new alleles in a gene pool
How do mutations arise?
DNA Damage: 1. Errors during DNA Replication 2. Spontaneous DNA Damage 3. Induced DNA Damage *Cells have several DNA repair systems, but every so often a mistake is made Certain parts of the DNA molecule are prone to spontaneous damage by water (hydrolytic attack) and free radicals (oxidative damage)
What is DNA sequencing?
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. It includes any method or technology that is used to determine the order of the four bases—adenine, guanine, cytosine, and thymine—in a strand of DNA. The advent of rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery. *The same principle as PCR, but only one primer, and some of the free nucleotides are fluorescently labeled and modified to terminate synthesis of the DNA strand. *Randomly terminates at every nucleotide position of the DNA strand
Who Emphasised the importance of variation and heredity in the evolutionary process
Darwin (1809-1882)
What is Genotype Frequencies?
Describe the gene pool quantitatively (must add up to 1.0)
What did Darwin do?
Emphasised the importance of variation and heredity in the evolutionary process
What is sunburn?
Exposure to UV light(from the sun, tanning lamps, etc) causes adjacent thymine (T) molecules to pair with each other. This damage halts the replication and transcription process, and can result in cell death
What is "Fitness"?
Fitness is represented as w and is the reproductive success of a genotype
Who Laid the cornerstone of modern population genetics: Hardy-Weinberg principle?
G. H. Hardy and W. Weinberg in 1908
How does Migration effect evolution?
Gene flow from other populations can alter allele frequencies
What is the equation for Mutation-Selection Balance?
If an allele is recessive, its equilibrium frequency is given by: q=square root (µ/s) *Where µ is the mutation rate, and s is the selection coefficient. *If s is small (the allele is only mildly deleterious) and µ is high, then the equilibrium frequency of the allele will be relatively high. *If s is large (the allele is highly deleterious) and µ is low, then the equilibrium frequency of the allele will be low.
What is Hardy-Weinberg Equilibrium Principle?
In a population of sexually reproducing diploid organisms, allele and genotype frequencies will remain constant (at equilibrium)unless some evolutionary process is operating to change them
What is an Example of Selection of an Allele?
In fruit flies: *Alcohol dehydrogenase(Adh): breaks down ethanol, a poison from rotting fruit *Two alleles at the Adh locus: AdhF and AdhS *Two populations of flies: (1) with food spiked with ethanol; and (2) with non-spiked food *In the treatment the AdhF genotype increased in frequency *The Alcohol dehydrogenase extracted from the AdhF individuals breaks down ethanol at twice the rate of the AdhS individuals *The frequencies of the two Adh alleles in Australian populations of fruit flies *The AdhS allele is generally at higher frequencies at lower latitudes (closer to the equator), whereas the AdhF allele is at a higher frequency at higher latitudes. The pattern is similar in Europe and North America. *The significance of this pattern is unclear, although it may relate to the fact that AdhS is more stable at higher temperatures
What is introgression?
In genetics (particularly plant genetics) is the movement of a gene (gene flow) from one species into the gene pool of another by the repeated backcrossing of an interspecific hybrid with one of its parent species. Purposeful introgression is a long-term process; it may take many hybrid generations before the backcrossing occurs.
What is the Wahlund effect?
In population genetics, the Wahlund effect refers to reduction of heterozygosity (that is when an organism has two different alleles at a locus) in a population caused by subpopulation structure. Namely, if two or more subpopulations have different allele frequencies then the overall heterozygosity is reduced, even if the subpopulations themselves are in a Hardy-Weinberg equilibrium. The underlying causes of this population subdivision could be geographic barriers to gene flow followed by genetic drift in the subpopulations *A single bout of random mating will put the population back into H-W equilibrium for genotype frequencies
What did E. B. Ford, P. M. Sheppard and H. B. D. Kettlewell?
In the U.K.: Genetic polymorphisms in natural populations (e.g. Industrial Melanism- Moths)
What did T. Dobzhansky do?
In the U.S.A.: Genetic variation in natural populations and speciation. "Nothing in biology makes sense except in the light of evolution".
Case study-How do we determine the CCR5 genotype?
Isolate DNA --> Amplify the target DNA sequence using PCR -->Distinguish the different size products (alleles) using gel electrophoresis
What did G. H. Hardy and W. Weinberg do?
Laid the cornerstone of modern population genetics: Hardy-Weinberg principle (1908)
How does fitness (w) fit with p and q?
Mean fitness in the population-----> Genotypes frequenecies after selection p2 + 2pq + q2 = 1.0-->p2w11(1.0) + 2pqw12(0.5) + q2w22(0.25) = w
Who Provided the mechanism for heredity ?
Mendel (1823-1884)
What is Allele frequencies?
Observed number of genotypes, or from the genotype proportions *The allelic frequencies for a locus, like the genotypic frequencies, should always add to 1.0 --p+q=1.0
How does mutation effect evolution as a force?
Over very long periods of time, mutation can eventually produce appreciable changes in allele frequencies
Case study: Molecular phylogenetics: how did HIV enter the human population?
Potentially from entered human population from interacting with moneys over time, and over time sprend through humans
What did Mendel do?
Provided the mechanism for heredity
How do we summarise genetic variation in a population?
Studying the genotype frequencies, and the use of Hardy-Weinberg Equilibrium Principle
Who wrote: Genetic variation in natural populations and speciation. "Nothing in biology makes sense except in the light of evolution".
T. Dobzhansky (1900-1975)
Case study: Detecting human resistance: where did the alleles that protect some people come from?
The CCR5-Δ32 allele confers resistance to HIV (fig: world map frequency of CCR5-Δ32
What happens when Hardy-Weinberg is extended to include more than two alleles?
The allele frequencies must add to one: p + q + r = 1.0 Then the genotypes frequencies are given by: p^2 + q^2 + r^2 + 2pq +2pr + 2qr = 1.0 and the allele frequencies do not change from generation to generation!
How much genetic variation do we expect to find in a population?
The amount of genetic variation in a population = population size & Mutation rate The Fisher-Wright Equation O = 4NeU O= genetic variation Ne = Effect population size U = Mutation rate per generation "The bigger the bucket the more it can hold"
How is Migration-change in allele frequency calculated (with two factors)?
The change in allelic frequencies from migration depends on two factors: Δp = m(1)(pM - pI (2)) (1) The proportion of migrants in the final population (2)The difference in allelic frequency between the migrants and the residents (e.g. pM - pI = 0.2 - 0.2 = 0) *Populations must differ in their allele frequencies for migration to affect the make up of the gene pool. With continual migration pM and pI become increasingly similar, and, as a result, the change in allelic frequency due to migration decreases
How is Migration-change in allele frequency calculated?
The frequency of the A1 allele in the island population after migration p'I = mpM (migrants) + (1 - m)pI (residenets) *Where m is the proportion of migrants that make up the new island population *The frequency of A1 after migration is determined by the proportion of A1 alleles in the two groups that now make up the island population
What is the additive effect?
The heterozygote has a mean phenotype exactly intermediate between the two homozygotes. For example, if the mean enzyme levels for the genotypes FF, FS and SS at the Adh locus are 100, 95 and 90 units of activity, respectively.
What is Polymerase Chain Reaction (PCR)?
The polymerase chain reaction (PCR) is a biochemical technology in molecular biology used to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence.
What is population genetics?
The science of population genetics attempts to describe the patterns of genetic variation and understand the evolutionary processes that have shaped that variation
What is Selection Coefficients?
The selection coefficient (s) is a measure of the relative intensity of selection on a genotype, and is 1 - w. The value of s can range from 0 - 1.0. In some cases s can be represented as a neg or pos. A positive selection coefficient means natural selection favours the variant; negative means it is selected against; zero means it is neutral.
What are the types of DNA changes?
There are two types of DNA changes: Transitions and Transversions *Transition type changes (A<-> G and C<-> T) are far more common than transversion type changes (A<-> C, A<-> T, G<->C and G<->T) because the physical changes to the structure of the nucleotide are more simple
What is the mathematical equation for Hardy-Weinberg Equilibrium principle?
Therefore random mating in the gene pool produces zygotes in the following proportions: AA (p^2) Aa (pq) aA (qp) aa (q^2) becoming: p^2 + 2pq + q^2 = 1.0 We have gone from the allele frequencies of the gene pool to genotype frequencies among zygotes
Who are the people who examined the theoretical consequences of Mendelian inheritance in natural populations?
Three people did: R. A. Fisher (1890-1962), J. B. S. Haldane (1892-1964) and S. Wright (1889-1988) do?
Who did Genetic polymorphisms in natural populations (e.g. Industrial Melanism- Moths)?
What did E. B. Ford, P. M. Sheppard and H. B. D.Kettlewell
Case study-Will the AIDS epidemic cause the frequency of the CCR5-Δ32 allele to increase in the human population?
Yes it possible could over many generations--> 1000s years -Selection is important, but the frequency affects the time it takes to make an effect, Impt info: (1) The relative fitness of the genotypes (2) The relative frequencies of the alleles in the population
What is a Mutation?
a mutation is a change of the nucleotide sequence of the genome of an organism, virus, or extrachromosomal geneticelement. Mutation can change Allele Frequencies