Genetics And The Modern Evolutionary Synthesis PDF

Topic 3 GENETICS AND THE MODERN EVOLUTIONARY SYNTHESIS Note: I assume you have a basic understanding of meiosis, but if you want a review see Chp. 13 of Campbell and/or the video in the ‘Additional Resources’ slide at the end of this lecture. 1  Learning objectives Compare/contrast...

Topic 3 GENETICS AND THE MODERN EVOLUTIONARY SYNTHESIS Note: I assume you have a basic understanding of meiosis, but if you want a review see Chp. 13 of Campbell and/or the video in the ‘Additional Resources’ slide at the end of this lecture. 1  Learning objectives Compare/contrast blending vs. particulate inheritance Outline the core ideas in Weismann’s germ plasm theory Explain Mendel’s three ‘laws’ of inheritance using modern genetic terminology and outline the core tenant of Mendel’s that remains true despite inheritance usually being more complex Map phenotype to genotype under different scenarios of dominance Draw a Punnett square to determine genotypes of offspring from specific crosses of two parental genotypes Use the addition and product rules of probability, and Punnett squares, to calculate probabilities of specific genotypes from given crosses Be familiar with modern genetic terms (e.g., locus, gene, allele, heterozygote, homozygote, phenotype, genotype) Explain the ways in which inheritance is often more complex than a simple ‘one locus-2 allele’ Mendelian model Describe the two reasons why many traits exhibit continuous variation. Calculate allele frequencies from genotype/phenotype frequencies or the reverse (by assuming HW) Understand the conceptual basis of HW expected genotype frequencies – i.e., Why are they p2, 2pq, q2? What assumptions are necessary for this to be true, and what does it mean if genotype frequencies differ from this? Conduct a test for HW genotype frequencies for a locus with two alleles: calculate expected # of individuals of each genotype under HW, compare these with observed # of individuals, and make an appropriate inference 2 Outline 3.1 Early theories of inheritance 3.2 Mendelian inheritance of simple traits 3.3 Inheritance is more complex 3.4 Re-discovery of Mendel and the Modern Evolutionary Synthesis 3.5 Hardy-Weinberg 3  Squididdily at en.wikipedia, Blending inheritance, CC BY-SA 3.0 3.1 Early theories of inheritance Blending inheritance Theory that phenotypes in offspring are an average (i.e., blend) of their two parents. Darwin had a version of this he called pangenesis in which all parts of the body produce particles of hereditary information (‘gemmules’) which accumulate in the gonads and are transferred to offspring. Environmental impacts could alter gemmule production, allowing for a Lamarkian idea of transmission of acquired characters Fleeming Jenkin argued that blending inheritance made natural selection ineffective because variation would soon be lost Experiments by Francis Galton on rabbits (1869-1871) were inconsistent with Darwin’s model of inheritance and the hypothesis fell out of favour 4 August Weismann A German (1834-1914), considered by some as one of the most notable evolutionary theorists after Darwin First grappled with evolution vs. creationism and came to the conclusion that many Unknown author, biological observations made complete sense in an evolutionary, but not creationist, August Weismann, marked as public domain, more details on context Wikimedia Commons Did experiments convincing him that Lamarkian inheritance of acquired characters didn’t work In 1892 developed his germ plasm theory for multi-cellular organisms proposing that heritable information was transmitted only by the germ cells in the gonads (i.e., the reproductive cells or gametes); all the other cells of the body – somatic cells – do not transmit such information, serving only to carry out all the bodily functions necessary for the transmission of the germ cells 5 The germ plasm theory germ cells produce somatic cells (the soma) anew each generation information flows from germ cells to somatic but not the other way the soma is disposable; the germ plasm is (potentially) immortal 6 Ian Alexander, Weismann's Germ Plasm, CC BY-SA 4.0  The germ plasm theory Situation is different in plants, corals, and sponges In these taxa, germ cells are produced by somatic cells (e.g., vegetative meristems in plants) and changes (i.e., mutations) in those somatic cells can affect subsequent germ cells derived from them, and hence be transmitted across generations 7 Schmid-Siegert et al. 2017. https://doi.org/10.1038/s41477-017-0066-9 Outline 3.1 Early theories of inheritance 3.2 Mendelian inheritance of simple traits 3.3 Inheritance is more complex 3.4 Re-discovery of Mendel and the Modern Evolutionary Synthesis 3.5 Hardy-Weinberg 8  Who was Gregor Mendel? Augustinian friar, born in part of the Austrian empire (today Czech Republic) From a farming family and struggled to pay for his education; became a monk in part because it provided free education Twice failed the exams to become a high school teacher; received training in Gregor Mendel, 1822- physics at University of Vienna 1884; Unknown author, marked as public domain, more details on Wikimedia Commons Now recognized as the founder of modern genetics From 1856-1863, Mendel cultivated and tested thousands of pea plants Analyzed his data with exemplary scientific rigour, developing mathematical predictions of his hypotheses to compare with observed results – he employed some of the principle of the scientific method From this he developed his principles of heredity 9  Mendel’s success Several of his choices were extremely judicious (lucky?): Many varieties of garden peas were available, they are easy to artificially cross and to grow, they have a short generation time and produce many descendants B. Ebbesen; CC BY-SA 3.0 He chose to work with discrete (binary polymorphisms) characters rather than quantitative (i.e., continuously variable) ones (e.g., size), and he used true-breeding (aka pure-breeding) plants He had the foresight to follow several successive generations of plants and record their traits, and crossed various combinations which provided insight into recessive characters 10 By LadyofHats, reworked by Sciencia58; CC0, https://commons.wikimedia.org/w/index.php?curid=82940368  Typical breeding experiment in a typical experiment, Mendel mated (crossed) two contrasting, true-breeding varieties parents are the P (parental) generation offspring of P generation are called F1 (first filial) generation When F1 individuals self- or cross-pollinate with other F1 hybrids, F2 generation is produced Fig. 14.,3 Campbell Biology, 3rd Canadian Edition. 2021. Pearson 11  Mendelian inheritance Observed that F1 plants were not a blend of the parents, but resembled one and not the other But the trait of the other parent, missing in the F1, reappeared in the F2; that is, the hereditary ‘factor’ wasn’t diluted or destroyed In the F2, there was consistently an approximate 3:1 ratio of the two phenotypes Mendel observed this pattern for 7 different traits Table 14.1, Campbell Biology, 3rd Canadian Edition. 2021. Pearson 12  Mendel’s model of particulate inheritance Mendel proposed a model in which heredity was controlled by ‘factors’ Distinct forms of these factors account for variation in phenotype Every individual has two factors, one inherited from each of their parents Example: life cycle of humans. Fig. 13.4 Campbell Biology, 3rd Canadian Edition. 2021. Pearson 13  Modern terminology Today we call these factors genes – a specific sequence of DNA (or sometimes RNA in viruses) that encodes the synthesis of a gene product (RNA or a protein) A locus (plural loci) is a broader term simply meaning a specific location (i.e., sequence of DNA) on a chromosome; a locus might or might not contain an actual gene (i.e., all genes are loci, but not all loci are genes) Alleles are unique variants of a gene that differ in nucleotide sequence (i.e., alleles are simply different sequences at a given locus) 14  Mendel’s ‘laws’ Variably referred to as Mendel’s laws, principles, or rules Very few phenotypes are purely Mendelian (meaning single gene with two alleles, one dominant over the other); most traits are influenced by multiple genes with varying dominance, and well as the environment Genetics, it turns out, is usually more complex than Mendel simple model – but Mendel was entirely correct in his fundamental idea that inheritance occurs via discrete factors that are passed intact from generation to generation according to the rules of probability Mendel 15  Mendel’s ‘law’ of dominance If two alleles at a locus differ, then one (the dominant allele) determines the phenotype and other (the recessive allele) has no noticeable effect F1 plants had purple flowers so the “purple allele” is dominant Fig. 14.3, Campbell Biology, 3rd Canadian Edition. 2021. Pearson 16 Fig. 14.4, Campbell Biology, 3rd Canadian Edition. 2021. Pearson  Mendel’s ‘law’ of segregation Alleles segregate independently during meiosis Fig. 14.3, Campbell Biology, 3rd Canadian such than a heterozygote (an individual with two Edition. 2021. Pearson different alleles at a given locus) produces 50% of their gametes carrying one allele and 50% carrying the other allele Aside: homozygote – an individual with two copies of the same allele at a given locus For a phenotype determined by a single gene with one dominant and one recessive allele, this predicts that if you cross two heterozygotes you should see a 3:1 ratio of dominant to recessive phenotypes in the offspring Punnett square: 17  Aside: Phenotype vs. genotype A phenotype is any quantifiable character/trait of an organism, whether morphological, behavioural, or physiological Genotype: the genetic makeup of an individual in terms of the identity of the alleles it carries at one or more loci There is not necessarily a 1:1 mapping of genotype to phenotype: Understand these terms and use them appropriately: phenotype genotype homozygous/heterozygous homozygote/heterozygote locus/loci gene/allele dominant/recessive Fig. 14.6 Campbell Biology, 3rd Canadian Edition. 2021. Pearson 18  Mendel’s ‘law’ of independent assortment Mendel derived his laws of dominance and segregation by studying individual traits in isolation F1 offspring were monohybrids (i.e., individuals that were heterozygous for one trait) A cross (hybridization) between such heterozygotes is called a monohybrid cross 19  Mendel’s law of independent assortment Mendel identified his law of independent assortment by following two traits at the same time Crossing two true-breeding parents differing in two traits produces dihybrids (i.e., individuals heterozygous for both traits) A dihybrid cross, a cross between two dihybrids, can determine if the two characters are transmitted together (‘dependently’) or independently From his studies, Mendel proposed the law of independent assortment: during gamete formation, alleles at a given locus segregate independently of those at other loci; in other words, the allele a gamete receives for one gene does not influence the allele it receives for another gene 20  Meiosis in a double heterozygote (i.e., dihybrid, AaBb) Independent assortment happens when non-homologous chromosome pairs independently align at the cell’s midpoint during metaphase 1, during which they can adopt one of two different alignments with equal probability. AaBb individual Watch it animated: https://youtu.be/uzNsw6p_THI 50% 50% A a A a B b b B Modified from: Fig. 13.1, Campbell Biology, 3rd Canadian Edition. 2021. Pearson AB AB ab ab Ab Ab aB aB 21 Q: do the alleles for colour and smoothness assort independently? Practice: Campbell Fig. 14.8 What If? question (solution in Appendix A) Cross a true-breeding yellow, smooth plant with a true-breeding green, wrinkly plant to produce F1 dihybrids. All F1’s to self-pollinate to produce F2’s (i.e., a dihybrid cross). What phenotypic ratios do you expect in the Ignore the left (‘dependent offspring? assortment’ side until later slide. 22  Probability governs Mendelian inheritance Mendel’s ‘laws’ of segregation and independent assortment reflect basic rules of probability Definition: events are independent when the outcome of one has no influence on the outcome of the other – when tossing a coin, outcome of one toss has no impact on outcome of next toss – during meiosis, alleles of one gene segregate into gametes independently of another gene’s alleles (e.g., when they are on different chromosomes) Multiplication (product) rule: the probability that two or more independent events will both occur is the product of their individual probabilities: Pr (A and B) = Pr(A) x Pr(B) 23  Probability governs Mendelian inheritance What’s the probability of an RR offspring from a cross between two Rr parents (i.e., a monohybrid cross)? whether gamete of parent 1 is R vs. r is independent of whether gamete of parent 2 is R vs r Pr(RR offspring) = Pr (R from parent 1) × Pr(R from parent 2) = 0.5 x 0.5 = 0.25 (i.e., 25%) Note: Pr(RR) = Pr (R from parent 1) AND Pr(R from parent 2) = Pr (R from parent 1) × Pr(R from parent 2) ‘AND’ is a hallmark of the multiplication (aka product) rule Fig. 14.9, Campbell Biology, 3rd Canadian Edition. 2021. Pearson 24  Probability governs Mendelian inheritance Addition (sum) rule – for outcomes that are mutually exclusive (i.e., only one can occur), the probability that any one of them occurs is the sum of their independent probabilities: Pr(A or B) = Pr(A) + Pr(B), assuming A and B are mutually exclusive. B A 25  Probability governs Mendelian inheritance E.g., assuming R is dominant over r and produces a red flower, what is the probability of a red- flowered offspring from a monohybrid cross between two Rr parents? Different offspring genotypes (i.e., RR, Rr, rR, rr) are mutually exclusive RR, Rr and rR all produce red-flower offspring; rr does not Pr(red offspring) = Pr(RR or Rr offspring) = Pr(RR) + Pr(Rr) + Pr(rR) = 0.25 + 0.25 + 0.25 = 0.75 (or 75%) Fig. 14.9 Campbell Biology, 3rd Canadian Edition. 2021. Pearson 26  Probability governs Mendelian inheritance Example: A double heterozygote (AaBb) mates with an AaBB individual. What is the probability their offspring is AABb? Optional review/practice: Assuming A and B loci assort independently: Concept Check 14.2 Campbell p. 294/296 Pr(AABb) = Pr(AA and Bb) = Pr(AA) x Pr(Bb) (3rd vs. 4th ed.) Pr(AA) in offspring of two Aa parents = 0.5 x 0.5 = 0.25 (or draw the Punnett square) Pr(Bb) offspring from Bb x BB mating = 0.5 (see below) So, Pr(AABb) = Pr(AA) x Pr(Bb) = 0.25 x 0.5 = 0.125 Parent 1 (Bb) B (0.5) b (0.5) Parent 2 (BB) B (1) BB (0.5) Bb (0.5) 27 Practice Hyperlink (click here), or: Q28 and Q29 28 Outline 3.1 Early theories of inheritance 3.2 Mendelian inheritance of simple traits 3.3 Inheritance is more complex 3.4 Re-discovery of Mendel and the Modern Evolutionary Synthesis 3.5 Hardy-Weinberg 29  Inheritance patterns are more complex 1) Mendel’s law of (complete) dominance is far from universal – dominant-recessive is a continuum and all possible intermediate phenotypes can, and often do, occur (called incomplete or partial dominance) – co-dominance also sometimes occurs (contribution of both alleles are distinctly visible in the phenotype) By darwin cruz - Flickr, CC BY 2.0 Wikipedia commons Fig. 14.10 Campbell Biology, 3rd Canadian Edition. 2021. Pearson Note: dominance/recessiveness has nothing to do with the frequency of an allele (e.g., polydactyl can be caused be a rare yet dominant allele in 30 humans)  Inheritance patterns are more complex 2) Alleles don’t always segregate independently within a locus (i.e., segregation is not always ‘fair’ in a heterozygote – i.e. 50:50 which allele is passed on) – E.g., meiotic drive is when a locus manipulates meiosis to favor the transmission of one allele over another – Most frequently observed affecting sex chromosomes; first discovered in Drosophila in 1928 Prof. Marcus Morton Rhoades, 1949 (Birchler et al. 2003. Genetics) – Later discovered in maize in the 1940’s and in animals in the 1950’s – E.g., in maize, Rr x rr test crosses produced 70% rr offspring – Meiotic drive is widespread across taxa (but rare within a genome), and is more common in some groups (e.g., Drosophila) than others 31  Inheritance patterns are more complex 3) Addition complications for single genes: Pleiotropy is when one gene affects multiple phenotypes; it is extremely common. The dominance/recessiveness relationship for a pair of alleles at a locus may vary depending on which phenotype is examined (e.g., the allele causing Tay-Sachs disease) There can be more than two alleles at a gene/locus (e.g., ABO blood type) 32 Source: Alphillips6; CC BY-SA 4.0; Wikimedia commons  Inheritance patterns are more complex 4) Assortment of alleles at one locus is often not independent of those at another locus – this often arises because the genes are close together (physically proximate) on a chromosome, a phenomenon termed physical linkage – alleles of physically linked genes tend to be inherited together Notice the missing Ab and aB gametes! A B A a B b a b 33 Inheritance patterns are more complex Humans have ~30,000 genes in their nuclear genomes, but only 23 pairs of chromosomes There are therefore MANY genes on a single chromosome Map of the ~85 million base pairs that form chromosome 18, showing physical location of a subset of the genes located on it. 34  Non-independent inheritance of body colour and wing phenotypes in D. melanogaster from the work of Thomas Hunt Morgan & Clara Lynch (1912); Fig. 15.9, Campbell Biology, 3rd Canadian Edition. 2021. Pearson b+ b vg+ vg 35  Inheritance patterns are more complex Recombination (i.e., cross-over events during meiosis) can produce the missing gamete types The probability of a recombination event between two loci on a chromosome increases as the distance between them increases Video correction: the homologous chromosome pairs line up 36 side-by-side on the spindle fibre.  Inheritance patterns are more complex 5) Epistasis occurs when one locus alters the effect on the phenotype of another, separate locus You can’t simply ‘add up’ the effects of the various alleles at the two loci: B vs. b have different effects on the phenotype in an individual that is E vs. e. There is epistasis here – an interaction between alleles at different loci in determining the phenotype. Source: Erikeltic; CC BY-SA 3.0; Wikimedia commons 37 Fig. 14.12, Campbell Biology, 3rd Canadian Edition. 2021. Pearson  Inheritance patterns are more complex 6) Many traits are quantitative, meaning they vary in a continuous manner (i.e., phenotypes do not fall into discrete categories). For example: height, blood pressure, hair colour, growth rate, maximum running speed, etc. The study of the genetics of continuously variable traits is a field called quantitative genetics. Quantitative variation arises because: i) Multiple, often many, loci affect the trait (i.e., it is polygenic – ‘poly’ meaning many) ii) An individual’s environment also affects expression of the trait 38  Polygenic traits i) Multiple, often many, genes affect the trait (i.e., it is polygenic) As the number of loci increases, phenotypic variation becomes very finely graded (closer and close to being truly continuous) (This is a tri-hybrid cross.) A simplified model of skin colour variation in humans with 3 loci having 2 alleles each. 7 discrete phenotypes are produced from a cross of two individuals that are heterozygous at all 3 loci. Fig. 14.13, Campbell Biology, 3rd Canadian Edition. 2021. Pearson 39  Polygenic traits ii) An individual’s environment also affects expression of the trait environmental impacts change finely graded discrete genetic variation into truly continuous phenotypic variation A simplified model of skin colour variation in humans with 3 loci having 2 alleles each. 7 discrete phenotypes are produced from a cross of two individuals that are heterozygotes at all 3 loci. 40 Outline 3.1 Early theories of inheritance 3.2 Mendelian inheritance of simple traits 3.3 Inheritance is more complex 3.4 Re-discovery of Mendel and the Modern Evolutionary Synthesis 3.5 Hardy-Weinberg 41 Rediscovery of Mendel’s work Mendel’s work was published in 1866 to little fanfare, going largely unnoticed by the scientific community (cited only a few times over the next 35 years) and blending inheritance remained the common view Evidence against blending inheritance was mounting, however, and in the early 1900’s two scientists, Hugo de Vries and Carl Correns, independently duplicated Mendel’s results Both later acknowledged Mendel’s priority and both of them (and a 3rd scientist, Erich von Tschermak) republished Mendel’s results 42  Biometricians vs. Mendelians Upon its rediscovery, the Mendelian theory of inheritance was not immediately accepted. A bitter debate raged for almost 20 years. – Biometricians (Francis Galton, Karl Pearson and colleagues) were focused on continuous traits, using statistical analyses of phenotypic variation to study heredity; they thought evolution involved gradual changes in continuous characters and they rejected Mendel’s ideas – Mendelians (William Bateson, Hugh de Vries, and others): focused on discrete traits and rejected gradual change; thought evolution occurred from selection acting on mutations of large effect (so called saltationism) 43  Reconciliation A full theoretical reconciliation among Mendelian genetics, the biometricians, and Darwin’s ideas of natural selection came through the work of R.A. Fisher, Sewall Wright, and J.B.S. Haldane starting in the 1920’s This founded the field of population genetics, which showed how continuous phenotypic variation could arise from a discrete Mendelian genetic basis, and how the statistical results of the biometricians could be generated by discrete genes/alleles Population genetics provided a rigorous mathematic framework of how selection and other processes (e.g., genetic drift) impacted Mendelian variation to produce evolutionary change 44 Outline 3.1 Early theories of inheritance 3.2 Mendelian inheritance of simple traits 3.3 Inheritance is more complex 3.4 Re-discovery of Mendel and the Modern Evolutionary Synthesis 3.5 Hardy-Weinberg 45  Hardy-Weinberg The formulation of the HW equation was necessitated from the criticism that, if Mendelian genetics were true, we should always see a 3:1 ratio of dominant to recessive phenotypes in a population (which we don’t) Y y F2 crosses Y Y y y Hardy and Weinberg responded in 1908 with what they thought was a mathematically obvious fact: that the genotype (and hence phenotype) frequencies will depend on the allele frequencies. In fact, they formulated the mathematical relationship between allele and genotype frequencies: 2 2 p + 2 pq + q = 1 46  Hardy-Weinberg principle 1) Under certain conditions, there is a predictable relationship between allele and genotype frequencies in a population which are expressed as the Hardy-Weinberg equation 2) Mendelian inheritance does not alter allele or genotype frequencies (once equilibrium conditions are met) across generations in a population. I.e., in the absence of evolutionary processes (e.g., natural selection, genetic drift), allele and genotype frequencies remain constant. 47  What is a population? Definition: a group of individuals of the same species that live in the same area and that interbreed A species can consist of >1 population Fig. 23.5, Campbell Biology, 3rd Canadian Edition. 2021. Pearson 48  Gene pools: genotype frequencies Gene pool consists of all copies of each allele at a given locus (a theoretical concept to aid our thinking) Number of plants 320 160 20 = a population of 500 plants Number of alleles 640 320 40 = a pool of 1,000 alleles Genotypes CRCR CRCW CWCW Observed genotype frequencies: freq. CRCR = # of CRCR individuals / total # of individuals = 320/500 = 0.64 Must sum to 1. freq. CRCW = # of CRCW individuals / total # of individuals = 160/500 = 0.32 Why? freq. CWCW = # of CWCW individuals / total # of individuals = 20/500 = 0.04 49  Gene pools: allele frequencies Number of plants 320 160 20 = 500 plants Number of alleles 640 320 40 = 1,000 alleles Genotypes CRCR CRCW CWCW Allele frequencies: p = freq. CR = total # of CR alleles/total # of alleles = ((320 x 2) + 160)/1,000 = 0.8 q = freq. CW = total # of CW alleles/total # of alleles = ((20 x 2) + 160)/1,000 = 0.2 Note: the sum of the frequencies of all alleles at a locus in a population must be 1 (e.g., p + q = 1 if there are only two alleles at the locus). Why? 50  Hardy-Weinberg assumptions 1. Diploid locus (i.e., two alleles) that reproduce sexually (note: you can do HW for loci with more alleles, it just gets a bit more complicated: (p + q + r)2 for 3 alleles) 2. Random mating with respect to the locus (i.e., random union of gametes) 3. No natural selection at the locus 4. No mutation at the locus 5. Individuals do not move in or out of the population (no migration) 6. Population is infinitely large (meaning no genetic drift) #3-6 are microevolutionary processes (i.e., that can cause evolution) 51  Hardy-Weinberg principle a a A A a A a A sperm or eggs Fig. 23.6, Campbell Biology, 3rd 52 Canadian Edition. 2021. Pearson  Hardy-Weinberg principle Fig. 23.7, Campbell We previously used a Punnett square to determine Biology, 3rd Canadian the offspring genotypes possible from a particular Edition. 2021. Pearson cross between two parents A Punnett square can also be used to determine expected genotype frequencies of offspring from random mating in an entire population This recognizes that the frequency of an allele in the population is equivalent to the probability that an allele picked at random from the gene pool is a copy of that allele e.g., p = Pr(randomly chosen gamete has allele CR) 53  Hardy-Weinberg principle Fig. 23.7, Campbell Therefore, if Hardy-Weinberg assumptions are met: Biology, 3rd Canadian Edition. 2021. Pearson p2 = expected freq. of genotype CRCR = 0.82 = 0.64 2pq = expected freq. of genotype CRCW = 2(0.8)(0.2) = 0.32 q2 = expected freq. of genotype CWCW = 0.22 = 0.04 And since the sum of all genotype frequencies at a locus must be 1, p2 + 2pq + q2 = 1 (assuming 2 alleles at a locus) So HW gives an expected relationship between allele frequencies in the PARENTS and genotype frequencies in their OFFSPRING (i.e., the next generation), when certain conditions are met. And from genotype frequencies in the offspring, we can calculate allele frequencies in the offspring (i.e., in the next 54 generation).  Hardy-Weinberg assumptions 1. Diploid organisms that reproduce sexually 2. Random mating with respect to the locus (i.e., random union of gametes) 3. No natural selection at the locus 4. No mutation at the locus 5. Individuals do not move in or out of the population (no migration) 6. Population is infinitely large (no genetic drift) Hardy-Weinberg describes the relationship between allele frequencies in parents and genotype frequencies in offspring under these assumptions. If observed genotype frequencies differ from Hardy-Weinberg expected genotype frequencies (e.g., p2, 2pq, q2), then it suggests one or more of the above assumptions are not met at this locus in this population. Assumptions 3-6 are processes of evolution (Topic 4); assumption 2 is not an evolutionary process, but is still interesting. Rejections of HW therefore indicate that something interesting going on at that locus. 55  Hardy-Weinberg in reverse If it’s reasonable to assume Hardy-Weinberg conditions, then allele frequencies can be estimated from genotype frequencies; i.e., q = sqrt root (freq. of # individuals with a recessive phenotype) Example – phenylketonuria (PKU) disease in humans (see Campbell, p. 523 for more details) PKU is a single-gene recessive metabolic disorder that occurs in ~1 out of 12,000 babies born in Canada Untreated it results in mental disabilities and other problems Harmful effects can be generally avoided via a diet low in phenylalanine HW assumptions seem reasonable, meaning q, the freq. of the mutant allele, can be estimated as: q2 = 1/12,000 = 0.0000833 56  Hardy-Weinberg homework Watch the 3 videos dealing with the Hardy-Weinberg principle on Brightspace Suggested practice – Concept check 23.2, p. 524/526 in Campbell (solutions in Appendix A) 57 Practice Kermode (aka Spirit) bears are rare individual black bears, Ursus americanus, that have a striking white (not albino) coat colour. They are found along the north coast of British Columbia. The phenotype is caused by a recessive mutation in the melanocortin 1 receptor gene, with the mutant ‘white’ allele, W, causing a white coat when homozygous, while the dominant A allele causes a black coat. A molecular assay was used to determine genotypes at this locus in a coastal island population. 100 bears in the population were genotyped and it was found that 69% were AA, 22% were AW, and 9% were WW. a) What are the frequencies of the A and W alleles in this population? 58 Practice Kermode (aka Spirit) bears are rare individual black bears, Ursus americanus, that have a striking white (not albino) coat colour. They are found along the north coast of British Columbia. The phenotype is caused by a recessive mutation in the melanocortin 1 receptor gene, with the mutant ‘white’ allele, W, causing a white coat when homozygous, while the dominant A allele causes a black coat. A molecular assay was used to determine genotypes at this locus in a coastal island population. 100 bears in the population were genotyped and it was found that 69% were AA, 22% were AW, and 9% were WW. a) What are the frequencies of the A and W alleles in this population? b) Are genotypes at this locus at Hardy-Weinberg equilibrium in this population? Show your calculations and clearly state your conclusion. 59  Topic 3: Additional resources Hardy-Weinberg videos on course website (Brightspace) Readings in Campbell Biology (in recommended order matching the lecture): – 13.1 – Chapter 14 to the end of 14.3 – 15.3 to end of the section ‘Recombination of Linked Genes: Crossing over’ – 23.2 Nice reviews of Mendel and Mendelian inheritance: https://www.youtube.com/watch?v=GTiOETaZg4w (whether Mendel ‘fudged’ some of his data, as Fisher argued, is not clear; see https://en.wikipedia.org/wiki/Gregor_Mendel for details) Independent assortment of chromosome during meiosis: https://youtu.be/uzNsw6p_THI Additional review of allele & genotype frequencies, Punnett squares, and Hardy-Weinberg – https://www.youtube.com/watch?v=Y1PCwxUDTl8&list=RDCMUCEik-U3T6u6JA0XiHLbNbOw&index=6 – https://youtu.be/oEBNom3K9cQ – https://www.youtube.com/watch?v=xPkOAnK20kw&list=RDCMUCEik-U3T6u6JA0XiHLbNbOw&index=2 For a complete review of meiosis see Chp. 13 in Campbell, and for a review of recombination during meiosis see: https://www.youtube.com/watch?v=nJZCYd4fspY (you can ignore the bit at end about recombinant mapping) 60