PCB 3

Genetic Bottlenecks • In genetic bottlenecks, a relatively large population is reduced to a small number by a catastrophic event unrelated to natural selection • Survivors of the bottleneck likely have a low level of genetic diversity and usually carry alleles in very different frequency than the original population • Loss of genetic diversity can be assessed by determining percentage of polymorphic loci in the population or the percentage of heterozygous loci in an average individual

20.6 Inbreeding Alters Genotype Frequencies but Not Allele Frequencies • If mating in a population is random, the distribution of alleles into genotypes occurs at frequencies consistent with those predicted in H-W equilibrium • Inbreeding, mating between related individuals, is a type of nonrandom mating that alters distribution of alleles into genotypes

Overview of Microevolution Genetic variation in natural populations changes over many generationsMicroevolution describes changes in a population's gene pool from generation to generation • Driven by: • Mutation • Random genetic drift • Migration • Natural Selection • Nonrandom mating

27.3 Natural Selection In the 1850s, Charles Darwin and Alfred RusselWallace independently proposed the theory of natural selection • According to this idea there is a struggle for existence • Those individuals that are most-adapted to their particular environment will survive and reproduce Recently population geneticists have realized that natural selection can be related to mating efficiency and fertility • Not just to differential survival

• Populations typically are dynamic units that change from one generation to the next - A population may change in • 1. Size • 2. Geographic location • 3. Genetic composition • Mathematical theories are used to predict how the gene pool will change in response to fluctuations in size, migration, and new environments

Allelic and Genotypic Frequencies Determining allelic and genotypic frequencies is central to population genetics Allele frequency =Number of copies of an allele in a population/Total number of all alleles for that gene in a population Genotype frequency =Number of individuals with a particular genotype in a population/Total number of all individuals in a population

Determine if a Population Exhibits HW Equilibrium (3 of 3) Expected frequency of NN= q2= (0.085)^2=0.007 • Expected number of NN individuals = 0.007 ×200 = ~1 Expected frequency of MN = 2pq = 2 × 0.915 × 0.085 = 0.156 • Expected number of MN individuals = 0.156 ×200 = ~31

Applying the Chi Square Formula (1 of 2) x^2=(o1-E1)^2 /E2+(03-E3)^2/E3

Population genetics part 2

Assumptions of Hardy-Weinberg Equilibrium H-W equilibrium serves as a model to calculate the frequencies of alleles and genotypes in a theoretical population that is infinitely large, practices random mating, and does not experience evolutionary change • Under these conditions, allele and genotype frequencies should remain constant • However, in nature, no population meets all the criteria for H-W equilibrium

Directional Selection for DDT Resistance Directional selection is shown with real data on resistance to DDT in a mosquito population

Balanced Polymorphisms A polymorphism may reach an equilibrium where opposing selective forces balance each other • The population is not evolving toward allele fixation or elimination • Such a situation is known as balancing selection It can occur because of different reasons 1. The heterozygote has a higher fitness than either homozygote, called heterozygote advantage 2. A species occupies a region that contains heterogeneous environments

Nonrandom Mating (2 of 2) Mating and genotypes • Inbreeding is the mating between genetically-related individuals • Outbreeding is the mating between genetically-unrelated individuals • In the absence of other evolutionary forces, allele frequencies are not affected by in- or out-breeding • However, these patterns of mating do disrupt the balance of genotypes predicted by the HW equation

Biological Species Can Be Defined in Many Ways • Different characteristics may be used to distinguish species - physical or morphological traits - ability to interbreed - reproductive isolation - molecular features - evolutionary relationships - ecological factors • The characteristics used may depend on the species in question

Chromosome theory of inheritance states that - Inheritance patterns of traits can be explained by transmission patterns of chromosomes during meiosis and fertilization • Theory based on the following observations - Chromosomes contain the genetic material - Chromosomes are replicated and passed from parent to offspring - Nuclei of most eukaryotic cells contain chromosomes in homologous pairs - In the formation of haploid cells, chromosomes segregate independently - Each parent contributes one set of chromosomes

Chromosome Theory of Inheritance links Mendel's principles with the movement of chromosomes during meiosis

• Meiosis I is followed by cytokinesis and then meiosis II • No chromosome/DNA replication prior to meiosis II • The events that occur during meiosis II are similar to those that occur during mitosis • However, starting point is different - For a diploid organism with six chromosomes • Mitosis begins with 12 chromatids joined as six pairs of sister chromatids • Meiosis II begins with 6 chromatids joined as three pairs of sister chromatids

Chromosome theory of inheritance 1. Mendel's studies 2. Nageli and Wiesmann -substance contributed equally by both parents controls traits in offspring 3. Boveri and Sutton - noted similarity between segregation and assortment of traits and behavior of chromosomes during meiosis

Lecture 12 Reproduction & Chromosomes

Chromosomes and Reproduction Review: Animal cells are of two types - Somatic cells • Body cells, other than gametes - Blood cells, for example - Germ cells • Gametes - Sperm and egg cells • Precursor cells that give rise to sperm and egg cells

Speciation • Speciation is the formation of new species via evolution • From fossils, evolutionary biologists have deduced two different patterns of speciation - Anagenesis • From the Greek, ana, meaning "up" and genesismeaning "origin" • A single species is transformed into a different species over the course of many generations - Cladogenesis • From the Greek, clados, meaning "branch" • A single species is divided into two or more species • This is the most common form of speciation

Cladogenesis • Divergent evolution is the most common form of speciation • Depending on geographic locations of evolving populations, speciation is characterized as - Allopatric • Two large populations separated by a geological barrier • Small founding population separates (founder effect) - Parapatric • Two populations overlap - limited amount of interbreeding - Sympatric • Population occupying single habitat evolves into reproductively isolated species

Disorders with X-Linked Recessive Inheritance Patterns • More common (over 850 identified) than X-linked dominant traits • Hemizygous males and homozygous recessive females are affected • Much more common in males, and for some rare traits, observed exclusively in males • Affected males pass the allele to all of their daughters but none of their sons - Daughters of affected males are heterozygous carriers and unaffected (if mother lacks allele) • Sons of heterozygous females have a 50% chance of inheriting the trait and being affected

Color Blindness: an X-linked Recessive Trait • Defective color vision caused by reduction or absence of visual pigments • Three forms: red, green, and blue blindness • About 8% of the male population in the US affected

The Chi Square Test The general formula is where • O = observed data in each category • E = anticipated data in each category based on the experimenter's hypothesis • { = Sum of the calculations for each category

Consider the following example in Drosophila melanogaster • Gene affecting wing shape - c+ = Normal wing (straight) - c = Curved wing • Gene affecting body color - e+ = Normal (gray) - e = ebony (black) • Note: - The wild-type allele is designated with a + sign - Recessive mutant alleles are designated with lowercase letters (without plus sign) • The Cross: - A cross is made between two true-breeding flies (c+c+e+e+ and ccee). The flies of the F1 generation are then allowed to mate with each other to produce an F2 generation.

Pedigree Analysis • Symbols used in a pedigree: • When analyzing, try to rule out inheritance patterns that are inconsistent with what the pedigree shows • Pedigrees may not rule out all but one possibility - Need to consider various potentials as hypotheses and make predictions about genotypes in current and future individuals - Consider probabilities • Recessive pattern of inheritance: - 1. Two unaffected heterozygous individuals (carriers) will average 25% of their offspring being affected - 2. Two affected individuals will produce 100% affected offspring - Can "skip" generations - If autosomal, both sexes affected with equal frequency - Affected individuals must have both parents be carriers (unless a new mutation has also occurred)

Cystic fibrosis (CF) - A recessive disorder of humans - Affected gene is the cystic fibrosis transmembrane conductance regulator (CFTR) - The mutant CFTR protein causes ion imbalance • Leads to abnormalities in many tissues and organs; pancreas, skin, intestine, sweat glands and lungs Cystic fibrosis as an autosomal recessive condition

Determine if a Population Exhibits HW Equilibrium (1 of 3) Use a chi square test to see if a population really exhibits HW equilibrium for a particular gene • Consider a human blood type called the MN type, determined by two codominant alleles, M and N • An Inuit population in East Greenland has 200 people • 168 were MM • 30 were MN • 2 were NN

Determine if a Population Exhibits HW Equilibrium (2 of 3) • Use the data to calculate the expected number for each genotype • If the chi square is too high, we would say the population is in disequilibrium • This might indicate evolutionary change f frequency Expected0.085 40030 + 2 2f(N)0.91540030 + 168 2f(M)=======22p• Expected number of MM individuals = 0.837 × 200 = ~167

Punnett square 1. Write down the genotypes of both parents - Male parent = Tt - Female parent = Tt 2. Write down the possible gametes each parent can make - Male gametes: T or t - Female gametes: T or t 3. Create an empty Punnett square 4. Fill in the possible genotypes of the offspring

Dihybrid crosses • Crossing individual plants that differ in two characters • There are two possible patterns of inheritance for these characters

20.2 Natural Selection Operates through Differential Reproductive Fitness within a Population • H-W equilibrium is maintained when there is random mating and no evolutionary change in a population • However, allele frequencies do change when evolution occurs • The evolutionary impact can be quantified by determining the change in allele frequencies Directional Natural Selection (1 of 2) • In directional natural selection, one phenotype with a homozygous genotype has a higher relative fitness than other phenotypes • Directional selection acts to increase the frequency of the favored allele over the others • For example, a case of codominant alleles of a gene, B1 (p = 0.60) and B2 (q = 0.40), with B1B1 having the highest relative fitness and B2B2 having the lowest

Directional Natural Selection, Progression to Fixation (1 of 2) • Directional natural selection will increase the frequency of certain alleles with variable intensity, depending on the strength of selection • If natural selection progresses for enough generations, the frequency of the favored allele will eventually become fixed at 1.0 and the unfavored allele will be eliminated • These fixed allele frequencies can be changed by mutation and migration, but not natural selection

Disruptive Selection Disruptive selection favors the survival of two or more different genotypes with different phenotypes • Also known as diversifying selection • Caused by fitness values for a given genotype that vary in different environments • Typically acts on traits that are determined by multiple genes

Disruptive Selection (Figure 27.12) (1 of 2) (a) Land snailsExample is a snail that lives in woods and open fields • brown shell color favored in woods with open soil • pink shell color favored in woods with leaf litter • yellow shell cover favored in sunny, grassy areas

20.4 Gene Flow Occurs by the Movement of Organisms and Genes between Populations • Gene flow refers to the movement of alleles into and out of populations, which can introduce novel alleles, increase frequency of existing alleles, or remove existing alleles • Gene flow is also known as migration • Gene flow derived from the addition of new organism to an existing population generates a new population called an admixed population

Effects of Gene Flow • Gene flow has two principal effects on population • In the short run, gene flow can change allele frequencies in the admixed population • In the long run, gene flow acts to equalize frequencies of alleles between populations that remain in genetic contact

Pleiotropic Effects • Cystic fibrosis as an example - Normal allele encodes the cystic fibrosis transmembrane conductance regulator (CFTR) - Regulates ionic balance by transporting Cl- ions - Mutant does not transport chloride effectively • In lungs, this causes very thick mucus • On the skin, causes salty sweat • Males are often sterile because Cl- transport is needed for proper development of the vas deferens - Defect in CFTR can have multiple effects

Epistasis • Inheritance of flower color in the sweet pea - Also discovered by Bateson and Punnett - Lathyrus odoratus normally has purple flowers • Bateson and Punnett obtained several true-breeding varieties with white flowers • They carried out the following cross - P: True-breeding purple X true-breeding white - F1: Purple-flowered plants - F2: Purple- and white-flowered in a 3:1 ratio • These results were not surprising But these results were: Complementation: Eachrecessive allele (c and p)is complemented by awild-type allele (C and P).This phenomenon indicatesthat the recessive allelesare in different genes. Epistasis: Homozygosityfor the recessive alleleof either gene results ina white phenotype, therebymasking the purple(wild-type) phenotype.Both gene productsencoded by the wild-typealleles (C and P) areneeded for a purplephenotype.

Directional Natural Selection, Progression to Fixation (2 of 2) • Directional natural selection against organisms with the recessive phenotype will cause the frequency of the dominant allele to increase and the recessive to decrease • Eventually the recessive allele may be completely eliminated • However, this can be a slow process, especially as the number of recessive homozygotes in the population decreases

Example: Laboratory Experiment on Directional Selection • Cavener and Clegg examined four subpopulations of Drosophila for 50 generations to test the effects of artificial directional selection in increasing the frequency of the allele AdhF (Adh-alcohol dehydrogenase) • The original population had allele frequency 0.38 • Two subpopulations were reared on ethanol-rich food, and two on food without ethanol; the populations on ethanol-rich food experienced AdhF allele frequency increases

Stabilizing Selection (1 of 2) In stabilizing selection, the extreme phenotypes are selected against • Intermediate phenotypes have the highest fitness values • Tends to decrease genetic diversity • Eliminates alleles that cause variation in phenotypes • Laying eggs is an example • Too many eggs drains resources to care for young • Too few eggs does not contribute many individuals to the next generation

Experiment 26A: Natural Selection in Galapagos Finches (1 of 2) Since 1973, Peter and Rosemary Grant have studied natural selection in finches found on the Galapagos Islands • Concentrated on moderately isolated island • Observed various traits such as beak size over many years • Depth of beak was transmitted from parents to offspring, regardless of environmental conditions (it is a heritable trait) • Differences are due to genetic differences in the population

Reasons for Differences in Reproductive Success Differences in reproductive achievement could be due to the 1. Fittest genotype is more likely to survive 2. Fittest genotype is more likely to mate 3. Fittest genotype is more fertileThis is the simplified case of single gene • Most traits are affected by variation in multiple genes Four Patterns of Natural Selection (1 of 2) Natural selection acts on phenotypes (which are derived from an individual's genotype) With regard to quantitative traits, there are four ways that natural selection may operate 1. Directional selection • Favors the survival of one extreme phenotype that is better adapted to an environmental condition 2. Balancing • Favors the maintenance of two or more alleles Four Patterns of Natural Selection (2 of 2) 4. Disruptive (or diversifying) selection • Favors the survival of two (or more) different phenotypes 5. Stabilizing selection • Favors the survival of individuals with intermediate phenotypes

Fate of a Beneficial Allele A mutation introduces the A allele into a population • The population was originally monomorphic for the a allele • Frequency of allele Aslowly rises at first • Rises much more rapidly at intermediate values • May be eventually fixed!Figure 27.7

Island Model of Migration • A one-way gene flow from population 1 into population 2 is described by the island model of migration • It depicts gene flow from a mainland population to an island population

Figure 20.7The Island Model of Migration The Founder Effect • Small population size provides the conditions under which sampling errors can produce significant genetic drift of allele frequency • Establishment of a new population by a small number of founding organisms can produce a difference in allele frequencies, and is called the founder effect • The allele frequencies of the new population may differ from the original population as a result of sampling error • The founder effect and genetic drift can result in high frequencies of autosomal recessive disorders in the new population that are rare in the original population

Darwinian Fitness Is a Measure of Reproductive Success A quantitative discussion of natural selection has to begin with a discussion of Darwinian fitness • Fitness is the relative likelihood that a genotype will survive and contribute to the gene pool of the next generation Darwinian fitness is a measure of reproductive superiority • It should not be confused with physical fitnessConsider a gene with two alleles, A and a • The three genotypic classes can be assigned fitness values according to their reproductive potential

Fitness Values Suppose the average reproductive success is • AA 5 offspring • Aa 4 offspring • aa 1 offspring By convention, the gene with the highest reproductive ability is given fitness value of 1.0 • The fitness values of the other genotypes are assigned relative to 1.0 Fitness values are denoted by the variable w AA:wAA=1.0 Aa:wAa=4/5=0.8 aa=waa=1/5=0.2

• Note the cross of two true-breeding mutant lines with the same phenotype producing wild-type offspring • This is called complementation - Complementation shows that the two mutant lines had the same phenotype caused by mutations in different genes

Gene redundancy • Loss of function alleles may have no effect on phenotype - One gene compensates for the loss of another • Paralogs - Homozygous gene knockout mice with no visible phenotype

Lecture 16 pop gen

Genes in Populations • Population genetics is a direct extension of Mendel's laws of inheritance, molecular genetics, and the ideas of Darwin • Instead of considering transmission of genes between individuals, population genetics considers the genes and their alleles within a population • All of the alleles of every gene in a population make up the gene pool - Only individuals that reproduce contribute to the gene pool of the next generation • Study of the genetic variation within the gene pool and how it changes from one generation to the next

• Consider a population of 100 frogs - 64 dark green with the genotype GG - 32 med. green with the genotype Gg - 4 light green with the genotype gg Frequency of allele g =Number of copies of allele gin the population/Total number of alleles G and gin the population HARDY-WEINBERG EQUILIBRIUM • Hardy-Weinberg equation formulated independently by Godfrey Harold Hardy and Wilhelm Weinberg in 1908 - Describes the expected frequencies for alleles and genotypes under a given set of conditions (described later) • The allele and genotype frequencies do not change over the course of many generations

Hardy-Weinberg Equation If a polymorphic gene exists in two alleles, A and a - The frequency of allele A can be denoted by the variable p - The frequency of allele a can be denoted by the variable q • By definition p + q = 1 - For this gene, the Hardy-Weinberg equation states that • (p + q)2 = 1 • p2 + 2pq + q2 = 1

• Prevalent alleles in a population are termed wild-type alleles • Proteins are made in the "right" amounts • Alleles typically are dominant - Can be more than one wild-type: genetic polymorphism • Mutant alleles are alleles that differ from wild-type • Can be recessive • Tend to be rare in natural populations • Loss of function - protein inactive or reduced in level • Can be dominant - may result from: • Function better - gain of function • Antagonize - dominant negative • Haploinsufficient - loss of function but heterozygote does not have wild-type trait Genetic diseases are caused by mutant alleles • In many human genetic diseases, the recessive allele contains a mutation - This prevents the allele from producing a fully functional protein

In a simple dominant/recessive relationship, the recessive allele does not affect the phenotype of the heterozygote - So how can the wild-type phenotype of the heterozygote be explained? 1. 50% of the normal protein is enough to accomplish the protein's cellular function 2. The heterozygote may actually produce more than 50% of the functional protein • The normal gene is "up-regulated" to compensate for the lack of function of the defective allele

The Coefficient of Inbreeding • Inbreeding: mating between related individuals • They will share a greater proportion of alleles with one another than random members of a population • The main genetic consequences of inbreeding will be an increase in the frequency of homozygous genotypes in a population and a decrease in the frequency of heterozygous genotypes

Inbreeding in Mammalian Populations • First-cousin mating is relatively common in many human societies and is common in mammals in general • First-cousin matings will produce a child with a recessive phenotype at a higher frequency compared to the risk by random mating • If a recessive allele is more frequent in a population, chances of a recessive homozygote in a first-cousin mating is only a few times more likely than in random mating

Incomplete Penetrance • The term indicates that a dominant allele does not always "penetrate" into the phenotype of the individual • The measure of penetrance is described at the population level - If 60% of heterozygotes carrying a dominant allele exhibit the trait, the trait is 60% penetrant • Note: In any particular individual, the trait is either penetrant or not

Incomplete Penetrance In some instances, a dominant allele is not expressed in a heterozygote individual • Example = Polydactyly - Autosomal dominant trait of additional digits - A single copy of the polydactyly allele is usually sufficient to cause this condition, but not always • Expressivity is the degree to which a trait is expressed - In polydactyly, number of digits varies - several extra digits means high expressivity - a single extra digit is low expressivity • Reason: effects of other genes or environment

Reciprocal crosses: determine sex linkage • Reciprocal cross - mate true-breeding individuals but change which sex has the trait • Duchenne muscular dystrophy (DMD) - Dogs and humans - X-linked recessive

Inference of sex linked inheritance through pedigree analysis X-linked dominant - If female has trait • Daughters can have trait (50% or 100% prob) • Sons can have trait (50% or 100% prob) - If male has trait • All of daughters have trait• None of sons have trait • X-linked recessive - Mother carrying allele without showing trait can have: • Usually no daughters have trait (unless father also contributes a mutant allele) • Sons may have trait (50%)• Y-linked - Only males affected

• Allele i is recessive to both IA and IB • Alleles IA and IB are co-dominant (in cells with both alleles the trait is a mixture of both phenotypes seen in the homozygotes)

Inheritance pattern of phenotypes can be different than what would be predicted from one gene/two alleles thatexhibit a strict dominance/recessive relationship

Dihybrid Crosses 1. Cross the two true-breeding plants toeach other. This produces F1 generationseeds. 2. Collect many seeds and record theirphenotype. 3. F1 seeds are planted and grown, and theF1 plants are allowed to self-fertilize.This produces seeds that are part of theF2 generation. 4. Analyze the characteristics found in theF2 generation seeds. Possibilities, not definite outcomes!

Interpreting the Data The F2 generation contains seeds with novel combinations not found in the parental generation - Round and Green - Wrinkled and Yellow • These nonparentals are predicted if the genes are segregating independently of each other (acting as if they are on different chromosomes or "particles")

Testing the Hypothesis (2 of 2) pic

Interpreting the Data 1976 was a wet year and the plants produced small seeds that the finches could all eat 1977 was a drought and the seeds that were available were larger and drier • Birds with large beaks could eat these more efficiently 1978 offspring had a clear increase in beak depth • Illustrates natural selection altering the nature of a trait

Sex-limited Traits Traits that occur in only one of the two sexes - Responsible for sexual dimorphism • For example, in humans - Breast development is normally limited to females - Beard growth is normally limited to males • In birds - males have more ornate plumage

Lethal Alleles • Essential genes are those that are absolutely required for survival - The absence of their protein product leads to a lethal phenotype • It is estimated that about 1/3 of all genes are essential for survival • A lethal allele is one that has the potential to cause the death of an organism - These alleles are typically the result of mutations in essential genes - They are usually inherited in a recessive manner

Other Monohybrid Crosses All of Mendel's monohybrid crosses yielded the same results - The F1 generation displayed only one parental trait - The trait not present in the F1 generation reappeared in 25% of the F2 generation - This result was seen regardless of which trait was contributed by the pollen • Refuted blending mechanism of heredity • Indicated particulate mechanism of heredity

Mendel's Conclusions Genetic factors (now known as genes) can be present but not expressed • Despite identical appearance, P1 and F1 plants must be genetically different • Although pea plants have two genes for each trait, they contribute only one to their offspring • Each plant carries two genetic factors for each trait, one from each parent. • Traits were not blended as they passed though parents

Modern Genetics: how is this relevant today? We are often interested in the relationship between the outcome of traits and the molecular expression of genes - Genes →Traits linkage • One approach: - Identify an individual with a defective copy of the gene: Loss-of-function allele - Observe how this copy will affect the phenotype of the organism - Often, mutations are induced to cause a loss-of-function allele • Gene knockouts, done with model genetic organisms

Mendelian Inheritance in Humans Segregation and independent assortment occur with human traits • Example: albinism - Albinos carry two copies of a mutant, recessive allele; cannot make melanin

Muscle Dystrophy: An X-Linked Recessive Trait • A group of genetic diseases associated with progressive degeneration of muscles • Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) have X-linked recessive inheritance patterns - Both caused by mutations in the dystrophin gene - DMD is more severe, because the dystrophin protein is defective or absent, while individuals with BMD have partially functional dystrophin proteins

Molecular Characteristics of DMD • In normal cells, dystrophin dissipates force of contraction along plasma membrane. • In Duchenne muscular dystrophy, dystrophin is defective and displaced, resulting in tearing of the plasma membrane during contraction and the subsequent death of muscle fibers

What is a Population? A population is a group of individuals of the same species that occupy the same region and can interbreed with each other A large population is usually composed of smaller groups called local populations • Members of a local population are far likelier to breed with each other than with members of the general population • Local populations are often separated from each other by moderate geographic barriers

Monomorphic and Polymorphic Genes Monomorphic - a gene that predominately has only one allele. Not very common. • Polymorphic - a gene with 2 or more alleles or a noncoding piece of DNA that shows variation in sequence within a population - more common than monomorphic Hawaiian happy-face spider:All individuals are from the same species, Theridiongrallator. Differ in alleles that affect color and pattern

• In General: - Overdominance is due to two alleles that produce slightly different proteins • Three possible explanations for overdominance at the molecular/cellular level 1. Disease resistance 2. Homodimer formation 3. Variation in functional activity

Multiple Alleles The carbohydrate chain on the surface of RBCs is composed of three sugars • A fourth can be added by the enzyme glycosyl transferase - The i allele encodes a "defective" enzyme; the carbohydrate chain is unchanged - IA encodes a form of the enzyme that can add the sugar N-acetylgalactosamine to the carbohydrate chain - IB encodes a form of the enzyme that can add the sugar galactose to the carbohydrate chain • Thus, the A and B antigens are different enough to be recognized by different antibodies

27.4 Genetic Drift Genetic drift refers to random changes in allele frequencies due to random fluctuations • Sewall Wright played a key role in developing this concept in the 1930s In other words, allele frequencies may drift from generation to generation as a matter of chance Over the long run, genetic drift favors either the loss or the fixation of an allele • The fixed allele is monomorphic and cannot fluctuate • The rate depends on the population size

Nonrandom Mating (1 of 2) Mating and phenotypes • Assortative mating occurs when individuals do not mate randomly • Positive assortative mating occurs when individuals are more likely to mate due to similar phenotypic characteristics • Negative assortative mating occurs when individuals with dissimilar phenotypes mate preferentially

Binomial Expansion Equation • Find probability of a subset from all of the possibilities for a given set of unordered independent events • Example: 3 out of 5 offspring will be affected P= n!/x! (n - x)! px qn - x • where - P = probability that the unordered outcome will occur - n = total number of events - x = number of events in one category - p = individual probability of x - q = individual probability of the other category

Note: - p + q = 1 - The symbol ! denotes a factorial • n! is the product of all integers from n down to 1 • 4! = 4 X 3 X 2 X 1 = 24 • An exception is 0! = 1 • Question - Two heterozygous brown-eyed (Bb) individuals have five children - What is the probability that two out of the couple's five children will have blue eyes?

Mendelian Genetics

Novelty of Mendel's work - Before Mendel, there was no clear understanding of how traits were inherited and passed from one generation to the next - Quantitative analysis of how some traits passed from one generation to the next - Developed Laws - • rules that allowed for the prediction of what phenotypes would appear in offspring • allowed for the prediction of what ratios of phenotypes would appear in offspring - Published work : Experiments on Plant Hybrids • Work ignored for many years (title problems?), then rediscovered in the early 1900's: Hugo de Vries, Carl Correns, Erich von Tschermak

Environment Environmental conditions may have a great impact on the phenotype of the individual - Some animals like the arctic fox change coat color • grayish brown in summer, white in winter - Humans affected by phenylketonuria (PKU) are unable to metabolize phenylalanine • symptoms include mental retardation - When detected early, individuals can be fed a restricted diet essentially free of phenylalanine and remain symptom free

Overdominance Overdominance is the phenomenon in which a heterozygote is more "vigorous" than both of the corresponding homozygotes - It is also called heterozygote advantage • Example = Sickle-cell disease - Autosomal recessive disorder - Affected individuals produce abnormal form of hemoglobin - Two alleles • HbA Encodes the normal hemoglobin, hemoglobin A • HbS Encodes the abnormal hemoglobin, hemoglobin S

Autosomal dominant traits Dominant pattern of inheritance - Does not "skip" generations - Affected individual will have at least one affected parent • However, disease may also result from a new mutation - Affected parents will average 50% of children being affected (when having children with unaffected partner) - Two affected people can have unaffected children (if they are both heterozygotes) - Often the homozygote dominant is more severely affected than the heterozygote - If autosomal, both sexes affected with equal frequency

PROBABILITY AND STATISTICS The laws of inheritance can be used to predict the outcomes of genetic crosses • EXAMPLES: - Animal and plant breeders are concerned with the types of offspring produced from their crosses - Parents are interested in predicting the traits that their children may have • This is particularly important in the case of families with genetic diseases

Lecture 13a Menelian extensions

Patterns of phenotypes that differ from those predicted by Mendel's Laws can be obtained when • The alleles do not have a simple dominant/recessive relationship • Phenotype is influenced by the environment • There is more than one gene that controls a single trait • There are more than two alleles for a gene that controls a trait • The genes are on the same chromosome • One allele is lethal • The trait is sex influenced or sex limited • There is gene redundancy

Mendelian Inheritance in Humans • Segregation and independent assortment occur with human traits• Example: albinism- Albinos carry two copies of a mutant, recessive allele; cannot make melanin

Pedigree Analysis Pedigree analysis is commonly used to determine the inheritance pattern of human genetic diseases • Genes that play a role in disease may exist as - A normal allele - A mutant allele that causes disease symptoms • Traits that follow a simple Mendelian pattern of inheritance can be - Autosomal dominant - Autosomal recessive • There can also be sex chromosome linked conditions - X-linked recessive - X-linked dominant - Y linked

Founder Effect and Genetic Drift • In allopatric speciation, geographical isolation creates a founder population - Founder effect: the allele frequencies established by chance from small founder population (may be even single fertilized female) • Over time, allele frequencies change in populations not at Hardy-Weinberg equilibrium (i.e. small populations) - Genetic drift: random fluctuation in allele frequencies seen in small populations

Phylogenetic Trees and Molecular Evolution • Phylogeny is the sequence of events involved in the evolutionary development of a species or group of species • A phylogenetic tree is a diagram that describes the phylogeny of a species - Depicts evolutionary relationship among species based on their homology with each other • Attributes that that are the result of homology are homologous - Clade - group of species with a common ancestor

Monohybrid crosses: Mendel's Study of Single Traits

Plants with round peas were crossed with plants with wrinkled peas (= P1 or parental generation) - All offspring (= F1 generation) produced smooth peas - F1 plants were crossed with each other to produce the F2 generation: • 5,474 plants with smooth peas • 1,850 plants with wrinkled peas • = 3:1 ratio of smooth:wrinkled

Mexican Hairless dogs When a Mexican hairless is mated to a different breed, about half of the puppies are hairless. When 2 Mexican Hairless are mated to each other, about 1/3 of surviving puppies have hair, about 2/3 of survivors are hairless, and about 1 out of 4 total puppies born are deformed and do not survive. • How do we show this type of inheritance?

Pleiotropic Effects • Most genes actually have multiple effects • Multiple effects of a single gene on the phenotype of an organism is called pleiotropy • Can be caused because - The gene product may affect cell function in multiple ways - The gene may be expressed in different cell types - The gene may be expressed at different stages of development

By definition p + q = _____ 1 We need a large population for Hardy Weinberg so that there is no... Random sampling error Phenotype refers to the specific allelic composition of an individual False Gametes are typically/normally... Haploid Hardy-Weinberg equilibrium can occur if there is migration and immigration. False Phenotypes describe... Physical characteristics Laying not too many and not too few eggs is an example of what selection type? Stabilizing

Populations are typically stable and usually do not change in size, geographic location, or genetic composition -False Land snails are an example of what kind of selection? Disruptive Inbreeding is the mating between genetically-related individuals True Males have XY sex chromosomes, females have XX. True A _________ allele is one that has the potential to cause the death of an organism Lethal True or false: Temperature can affect sex determination in some animals. True A group of species with a common ancestor is called a/n... clade

Principles of Natural Selection (1 of 2) A modern description of natural selection can relate molecular genetics to the phenotypes of individuals 1. Within a population there is allelic variation arising from various factors such as mutations causing differences in DNA sequences • Distinct alleles may encode proteins of differing functions 2. Some alleles may encode proteins that enhance an individual's survival or reproductive capacity

Principles of Natural Selection (2 of 2) 3. Individuals with beneficial alleles are more likely to survive and reproduce 4. Over the course of many generations, allele frequencies of many different genes may change through natural selection • This significantly alters the characteristics of a species • The net result of natural selection is a population that is better adapted to its environment and/or more successful at reproduction

Sum rule • The probability that one out of two or more mutually exclusive events will occur is the sum of their respective probabilities - Basically, add alternative probabilities together • Cross TtYy pea plant with ttYy pea plant • What is probability of tall yellow or tall green pea plants?

Product rule • The probability that two or more independent events will occur is equal to the product of their respective probabilities • Note - Independent events are those in which the occurrence of one does not affect the probability of another • Independent is the opposite of mutually exclusive • Example: occurrence of a trait in specified number of offspring - Cross Tt and Tt pea plant, what is probability that 4 out of 4 plants will be tall?

Genotype Frequencies • The genotype frequencies can be computed using the binomial expansion (p + q)2 • The two p + q terms represent male and female contributions to mating • The summation of the genotype frequencies is p2 + 2pq + q2 = 1.0, where p2 = frequency of A1A1, 2pq = frequency of A1A2, and q2 = frequency of A2A2 Random Mating • Random mating for one generation produces genotype frequencies that can be predicted from allele frequencies • For any frequency of p and q, an expected equilibrium distribution of genotype frequencies can be derived • With random mating and no evolutionary change, these frequencies will remain constant from one generation to the next

Random Mating Leads to Predictable Genotype Frequencies • Parental genotypes unite to reproduce at proportions predicted by their frequency • If parents have the same genotype, there is no reciprocal mating to account for, but in cases where the parents have different genotypes, the reciprocal matings must be included • The progeny of each mating are predicted according to Mendelian principles

Random Assortment and Crossing Over In Prophase I, homologous chromosomes physically pair with one another. Crossing over takes place between non-sister chromatids. There is a physical exchange of chromosome segments and the genes they carry. Crossing over generates new combinations of Mom's and Dad's alleles. Metaphase I: Random assortment of chromosomes

Result of Meiosis I: - The two pairs of sister chromatids (i.e. the homologous chromosomes) separate from each other - The connection that holds sister chromatids together does not break - Sister chromatids reach their respective poles and decondense - Nuclear envelope reforms to produce two separate nuclei

Mendel's Principle of Segregation 1. For a given character, a pea plant contains two discrete hereditary factors, one from each parent 2. The two factors may be identical or different 3. When the two factors of a single character are different - One is dominant and its effect can be seen - The other is recessive and the trait is not seen 4. During gamete formation, the paired factors segregaterandomly so that half of the gametes receive one factor and half of the gametes receive the other

Review of Terms: - Mendelian factors are now called genes - Alleles are different versions of the same gene - An individual with two identical alleles is termed homozygous - An individual with two different alleles, is termed heterozygous - Genotype refers to the specific allelic composition of an individual - Phenotype refers to the outward appearance of an individual

• In diploid organisms: Members of a pair of chromosomes are called homologs - The two homologs form a homologous pair • The two chromosomes in a homologous pair - Are nearly identical in size - Have the same banding pattern when stained - Have the same centromere location - Have the same genes • But not necessarily the same alleles - There is usually less than 1% sequence difference between homologs

SEXUAL REPRODUCTION • Most common way for eukaryotic organisms to produce offspring - Parents make gametes with half the amount of genetic material • process of forming gametes: gametogenesis • gametes fuse with each other during fertilization to begin the life of a new organism • Gametes are typically haploid (single set of chromosomes) - Chromosomes must be correctly distributed • Each gamete must receive one chromosome from each pair

Many lethal alleles prevent cell division - These will kill an organism at an early age • Some lethal alleles exert their effect later in life - Huntington disease • Characterized by progressive degeneration of the nervous system, dementia and early death • The age of onset for the disease is usually between 30 to 50 • Conditional lethal alleles may kill an organism only when certain environmental conditions prevail - Temperature-sensitive (ts) lethals • A developing Drosophila larva may be killed at 30o C • But it will survive if grown at 22o C

Semilethal alleles - Kill some individuals in a population, not all of them - Environmental factors and other genes may help prevent the detrimental effects of semilethal genes • A lethal allele may produce ratios that seemingly deviate from Mendelian ratios • Manx cat - Carries a dominant mutation that affects the spine - This mutation shortens the tail - This allele is lethal as a homozygote

Sex-Linked Inheritance Involves Genes on the X and Y Chromosomes Genes on sex chromosomes have distinct patterns of inheritance - Males (XY) • Pass an X chromosome onto all of their daughters, but none of their sons • Pass a Y chromosome onto all of their sons, but none of their daughters - Females (XX) pass an X chromosome to all of their children • Most genes on the X chromosome are not found on the Y chromosome

Sex Linked Genes • Some genes unique to X or Y - sex-linked • Females have two X chromosomes - Females can be heterozygous or homozygous for X-linked traits • Males have only one X chromosome - Males are hemizygous for X-linked traits - Males carrying one X-linked recessive allele express the recessive phenotype

Sex and Traits The inheritance pattern of certain traits is governed by the sex of the individual • These traits are of two main types - Sex-influenced - Sex-limited

Sex-influenced Traits • Traits where an allele is dominant in one sex but recessive in the opposite sex - Thus, sex influence is a phenomenon of heterozygotes • Sex-influenced does not mean sex-linked- Most sex-influenced traits are autosomal Example: Pattern baldness

Why pea plants are good genetic models: - Small, easily grown - Each flower has male and female structures so that • One plant can be used to fertilize itself (selfing/selfed) • One plant can be bred to another different plant Crossed/crossing/cross fertilization - Many different varieties were available that had different characteristics • Flower color • Stem length • Appearance of pods and seeds • Height • Flower position

Started with plants that bred true for different character traits • True-breeding lines - mating a plant to itself or another plant with same trait resulted in offspring with the same trait • This means that the trait of interest did not vary in appearance from generation to generation • Mated true-breeding plants with one character to plants with a different character to create hybrids - Matings looking at one character - monohybrid cross - Matings looking at two characters - dihybrid cross

The outcome - F1 generation • All offspring have straight wings and gray bodies - F2 generation • 193 straight wings, gray bodies • 69 straight wings, ebony bodies • 64 curved wings, gray bodies • 26 curved wings, ebony bodies • 352 total flies • Applying the chi square test - Step 1: Propose a hypothesis that allows us to calculate the expected values based on Mendel's laws • The two traits are independently assorting - Step 2: Calculate the expected values of the four phenotypes, based on the hypothesis • According to our hypothesis, there should be a 9:3:3:1 ratio in the F2 generation

Step 4: Interpret the chi square value - The calculated chi square value can be used to obtain probabilities, or P values, from a chi square table • These probabilities allow us to determine the likelihood that the observed deviations are due to random chance alone - Low chi square values indicate a high probability that the observed deviations (from expected) could be due to random chance alone - High chi square values indicate a low probability that the observed deviations are due to random chance alone If the chi square value results in a probability that is less than 0.05 (i.e.: less than 5%) • The hypothesis is rejected, i.e. the deviation from hypothesized is not due to chance ("wrong" hypothesis).

MEIOSIS Like mitosis, meiosis begins after a cell has progressed through interphase of the cell cycle • Unlike mitosis, meiosis involves two successive divisions - These are termed Meiosis I and II - Each of these is subdivided into • Prophase • Prometaphase • Metaphase • Anaphase • Telophase

Summary of Chromosome Movement during Meiosis Members of chromosome pair Each chromosome pairs with its homologueCrossing over occurs Paired homologues separate in meiosis I Sister chromatids separate and become individual chromosomes in meiosis II

Experiment 26A: Natural Selection in Galapagos Finches (2 of 2) The Hypothesis • Beak size will be influenced by natural selection. Environments that produce large seeds will select for birds with large beaks

Testing the Hypothesis (1 of 2) 1. In 1976, measure beak depth in parents and offspring of the species G. fortis. 2. Repeat the procedure on offspring that were born in 1978 and had reached mature size. A drought had occurred in 1977 that caused plants on the island to produce mostly larger seeds and relatively few small seeds.

• Applying the binomial expansion equation - Step 1: Calculate the individual probabilities • This can be obtained via a Punnett square P(blue eyes) = p =1/4 P(brown eyes) = q = 3/4 - Step 2: Determine the number of events • n = total number of children = 5 • x = number of blue-eyed children = 2 - Step 3: Substitute the values for p, q, x, and n in the binomial expansion equation

The Chi Square Test • A statistical method used to determine goodness of fit - Goodness of fit refers to how close the observed data are to those predicted from a hypothesis Note: - The chi square test does not prove that a hypothesis is correct • It evaluates whether or not the data and the hypothesis have a good fit - Null hypothesis: no difference between observed and expected - Alternate hypothesis: there IS a difference between observed and expected

The Chi-Square Test of Hardy-Weinberg Predictions • The assumptions of H-W equilibrium are unattainable in real populations • The chi-square test can be used to determine whether observed genotype frequencies in populations are significantly different from those predicted by H-W equilibrium • If chi-square analysis shows significant deviation from H-W equilibrium expectations, the cause can be investigated

The Hardy-Weinberg Equilibrium • The simplest predictions of H-W equilibrium involve two alleles of an autosomal gene, A1 and A2 • The frequencies for these are given as f (A1) = p and f (A2) = q, with equal frequencies in males and females • Since there are only two alleles of the gene, p + q = 1.0 • For the two alleles, there are three possible genotypes: A1A1, A1A2, and A2A2

- Caused by an autosomal gene • Allele B behaves as dominant in males, but recessive in females • Results from overexpression of gene that converts testosterone to 5-α-dihydrotestosterone (DHT), this binds to cellular receptors and alters the expression of many genes

The autosomal nature of pattern baldness has been revealed by analysis of human pedigrees What must be true about female II-5?Is it guaranteed that all children of III-9 and III-10 would have trait?

Probability The probability of an event is the chance that the event will occur in the future • Probability =Number of times an event is predicted to occur/Total number of possible events For example, in a coin flip P heads= 1 heads/ (Number of times an event is predicted to occur(1 heads + 1 tails) = 1/2 = 50%

The larger the size of the sample, or number of times the experiment is performed, the more closely the observed results will match the expected outcomes - due to random sampling error • Probability calculations are used in genetic problems to predict the outcome of crosses • To compute probability, there are three mathematical operations commonly used - Sum rule - Product rule - Binomial expansion equation

HbSHbS (homozygous recessive) have sickle cell disease condition 1. Sickling shortens the life span of the red blood cells - Anemia results 2. Odd-shaped cells clump - Partial or complete blocks in capillary circulation • Found at a fairly high frequency in parts of Africa where malaria is found - Malaria is caused by a protozoan, Plasmodium sp. - This parasite undergoes its life cycle in two main parts • One inside the Anopheles mosquito• The other inside red blood cells • Red blood cells of heterozygotes are likely to rupture when infected by Plasmodium sp. - Prevents the propagation of the parasite

Therefore, HbAHbS individuals are "better" than: - HbSHbS, because they do not suffer from sickle cell disease - HbAHbA, because they are more resistant to malaria - However, they are a carrier of the allele

Which of the following is a germ cell? Sperm cell Darwinian fitness is a measure of... Reproductive success Favoring the survival of individuals with intermediate phenotypes is what kind of selection? Stabilizing A skin cell would be an example of a somatic cell. True Assortative mating occurs when individuals do not mate randomly True When does crossing over occur? Prophase I

describes changes in a population's gene pool from generation to generation -Microevolution If a heterozygote has a higher fitness than either homozygote, that is called heterozygote advantage. -True Which of the following is the longest phase of the cell cycle? -Interphase A single species is transformed into a different species over the course of many generations is... -Anagenesis Biological females have 44 autosomes and sex chromosomes X and Y. -False All of the alleles of every gene in a population make up the... -Gene pool A _________ is a group of individuals of the same species that occupy the same region and can interbreed with each other -Population Resistance of mosquitos to DDT shows what kind of selection? Directional

Consider the disease congenital analgesia - Recessive trait in humans - Affected individuals can distinguish between sensations • However, extreme sensations are not perceived as painful - Two alleles • P = Normal allele • p = Congenital analgesia • Question - Two heterozygous individuals plan to start a family - What is the probability that the couple's first three children will all have congenital analgesia?

• Applying the product rule - Step 1: Calculate the individual probabilities • This can be obtained via a Punnett square P(congenital analgesia) = 1/4 - Step 2: Multiply the individual probabilities1/4 X 1/4 X 1/4 = 1/64 = 0.016 = 1.6%

• Looks like Mendelian dihybrid cross results but all genotypes having one homozygous recessive gene have recessive phenotype • Bateson and Punnett reasoned that flower color is determined by two different genes - C (one purple-color-producing) allele is dominant to c (white) - P (another purple-color-producing) allele is dominant to p (white) - cc or pp masks P or C alleles, producing white color - Thus, a plant that is homozygous for either recessive white allele, would develop a white flower • Regardless of whether or not the other gene contains a purple-producing allele

• Epistasis is the situation in which a gene can mask the phenotypic effects of another gene • Epistatic interactions often arise because two (or more) different proteins participate in a common cellular function - For example, an enzymatic pathway • If an individual is homozygous for either recessive allele- It will not make a functional enzyme required for the production of purple pigment: (cc) no enzyme C, (pp) no enzyme P - Therefore, the flowers remain white

Relationship between Gene and Allele Frequencies The HW equation provides a quantitative relationship between the allele and genotype frequencies • Figure 27.5 • GG dominates when g is high • Gg dominates when both allele frequencies are intermediate • gg dominates when g is high

• In reality, no population satisfies the Hardy-Weinberg equilibrium completely • However, in some large natural populations there is little migration or natural selection of any particular gene - In these cases, the HW equilibrium is nearly approximated for certain genes • Can be used to determine frequencies of heterozygote carriers of recessive traits in a population - i.e. cystic fibrosis 1/2500 affected in European-Americans - Also for X-linked traits, among females

Predicted phenotype (outward appearance) ratio in the F2generation would be 9:3:3:1 if genes act independently of each other • Principle of Independent Assortment- During gamete formation, the segregation of any pair of hereditary determinants (genes) is independent of the segregation of other pairs Independent assortment is also revealed by a dihybrid test-cross - TtYy X ttyy Test-cross involves a homozygous recessive indiv.(Tall, yellow) (Dwarf, green)

• Independent assortment is also revealed by a dihybrid test-cross -TtYy X ttyy Test-cross involves a homozygous recessive indiv.(Tall, yellow) (Dwarf, green) Thus, if the genes assort independently, the expected phenotypic ratio among the offspring is 1:1:1:1

Compare Hardy-Weinberg and Punnett Square Compares Hardy-Weinberg equation with the Punnett square approachThe frequency of gametes carrying a particular allele is equal to the allele frequency for a population in Hardy-Weinberg equilibrium. • Multiplying the allele frequencies gives the proportion of each allele combination in the population.

• The Hardy-Weinberg equation predicts an equilibrium if certain conditions exist in a population - 1. No new mutations - 2. No genetic drift. The population is so large that allele frequencies do not change due to random sampling errors - 3. No migration - 4. No natural selection - 5. Random mating • Basically the frequencies are not changing in population over time • The HW equation provides a quantitative relationship between the allele and genotype frequencies

Hardy-Weinberg: Allele Frequencies • All allele frequencies for a given trait in a population must add up to 100% or 1.00 • Measuring allele frequency - p = frequency of the dominant allele (A) - q = frequency of the recessive allele (a)• Therefore, p + q = 1 Important note:These are for alleles in a population, not an instance of mating between 2 individuals

• To determine if the genes or genotypes of a population are not changing, the expected frequencies of the different genotypes can be calculated and compared to what is observed • If p = 0.8 and q = 0.2, then the expected frequencies of the different genotypes in a population that is not changing can be determined - frequency of AA = p2 = (0.8)2 = 0.64 - frequency of Aa = 2pq = 2(0.8)(0.2) = 0.32 - frequency of aa = q2 = (0.2)2 = 0.04