Exam 1, Fall 2012 Grade Summary. Points: Mean 95.3 Median 93 Std. Dev 8.7 Max 116 Min 83 Percentage: Average Grade Distribution:

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1 Exam 1, Fall 2012 Grade Summary Points: Mean 95.3 Median 93 Std. Dev 8.7 Max 116 Min 83 Percentage: Average 79.4 Grade Distribution:

2 Name: BIOL 464/GEN 535 Population Genetics Fall 2012 Test # 1, 09/26/2012 Please answer all questions unless otherwise specified. Show as much of your work as you can! Use the back of the page and additional sheets as necessary. ********* means you may see something covering this topic on the next exam Part One. Multiple Choice. Circle the term that does NOT apply. (2 points each) 1. Assumptions of Hardy-Weinberg Equilibrium (15 of 19 correct in class) a. Large population b. Random mating c. No immigration d. No dominance 2. Allele frequency estimate (10 of 19 correct in class)*********** a. 2N11 + N b p q Q + H 2N 2 n c. 1 d. Nii + Nij 2 j 1 pi, j i N N11 P N 3. Completely recessive alleles (6 of 19 correct in class)********** a. h0 b. Difficult to eliminate from a Hardy-Weinberg population with selection c. Phenotypic effects undetectable in heterozygotes d. Cause reduced fitness Fitness effects (selective coefficients and heterozygosity are different phenomena. Recessive alleles could enhance fitness in principle. 4. Inbreeding (18 of 19 correct in class) a. Affects all loci in the genome b. Increases homozygosity c. Alters allele frequencies d. Increases probability of identity by descent of two alleles in a population 5. Purifying selection (13 of 19 correct in class) a. Affects all loci in the genome b. Increases homozygosity c. Alters allele frequencies d. Reduces diversity

3 6. Overdominance (11 of 19 correct in class)************ a. Final allele frequencies depend on starting allele frequencies b. Heterozygote has higher relative fitness than either homozygote c. Results in a stable equilibrium of allele frequencies d. Can help maintain diversity within a population Perhaps this is worded poorly, but the point is that the equilibrium point is determined only by the selection coefficients 7. Microsatellites (9 of 19 correct in class)************* a. Typically more diverse than allozymes b. Polymorphisms caused by slippage of DNA polymerase c. Usually dominant d. Primers usually amplify a single locus in a genome Microsats are usually codominant because the polymorphism is based on length differences, so different alleles are visible in the same lane 8. Mendel (16 of 19 correct in class) a. Developed the law of independent segregation b. Was a great influence on Darwin s theory of evolution by natural selection c. Used pea plants as one of his main model systems d. Explained how phenotypes can skip a generation 9. Transposable elements (17 of 19 correct in class) a. Are one of the primary determinants of genome size in complex eukaryotes b. Are only present in plants c. Are related to viruses d. Can move around the genome and cause phenotypic changes Looks like Dr. Hawkins is a better lecturer 10. Fixation index (9 of 19 correct in class)************ a. A measure of the deviation of observed heterozygosity from that expected under Hardy-Weinberg equilibrium b. Expected to be higher in an inbreeding population c. Can never be negative d. Can be used to estimate probability of identity by descent in some cases Fixation index can be negative when observed heterozygosity exceeds expected heterozygosity. If you re trying to imagine a situation in which this might happen, see problem 6 above. This was a case where I was hoping you would look at the equation and reason it through.

4 Part Two. 1. Narcolepsy in Doberman Pinschers is caused by a completely recessive allele, canarc-1. A breeder mates two Dobermans that are carriers (heterozygotes) of this allele. What is the probability that no narcoleptic offspring will be born in a litter of 6 puppies? (10 points) Average score: 8.63 Probability of success is 0.25 Aa x Aa 0.25 AA 0.5 Aa 0.25 aa Where aa is the only narcoleptic genotype Use the binomial probability equation: n y P( Y y) p y q n. y! P(Y 0) # 6$ " 0% & The frequency of narcolepsy in a population of 1000 Dobermans is approximately a. What is the frequency of the canarc-1 allele in this breed? (5 points) (avg score: 2.63)************* q b. What are the main assumptions of this calculation (undergrads: list at least 2; grads, at least 3)? (6 points) (avg score: 5.84) 1. Hard-Weinberg equilibrium (and all underlying conditions) 2. canarc-1 is the only cause of narcolepsy in this population 3. All homozygous canarc-1 dobermans will have narcolepsy (i.e., the trait is completely penetrant) c. What is the standard error of this estimate? (5 points) (Avg score: 4.31) Dominant trait, so use the variance for dominant loci: var q 1! q2 4N 1!

5 3. A genetic test now exists for the canarc-1 allele. Genotype frequencies in Dobermans are as follows: canarc-1/canarc /canarc /+ 600 a. What is the frequency of the canarc-1 allele? (5 points) (avg score: 4.57)********** q N N 12 N b. What is the standard error of this allele frequency estimate? (5 points) (avg. score 2.63)********* This is now a codominant locus because the genetic test allows us to distinguish both alleles in a heterozygote var q q(1! q) 2N (0.3)(0.7) c. Is this population in Hardy-Weinberg Equilibrium? (10 points) (avg. score 8.63)******* See Excel Sheet. There were an inordinate number of calculation errors on this problem. I recommend learning how to do this in excel. Total Chi-Square value is Degrees of Freedom Critical value is Since the calculated Chi-square value greatly exceeds the critical value, there is insufficient evidence to support the null hypothesis that the observed genotype frequencies are not different from those expected under Hardy-Weinberg Equilibrium. The Null Hypothesis is therefore rejected and we conclude that the population is not in Hardy-Weinberg equilibrium.

6 d. What are some likely biological explanations for the differences in allele frequency estimates based on observations of the narcolepsy phenotype versus direct determination using molecular tests? (Graduate Students, provide at least 2 different explanations) (10 points) (avg. score 9.1) There is an excess of homozygotes and a deficiency of heterozygotes compared to what would be expected under Hardy-Weinberg. This may indicate some inbreeding within the Doberman lineage, which would not be unusual in a pure dog breed. It is interesting that there is a larger excess of narcoleptic dogs compared to expected. Perhaps there is some selection occurring, either directly favoring Narcolepsy (perhaps some people like dogs that sleep all the time??) or indirectly because the canarc-1 allele has unknown pleiotropic effects that enhance fitness. Underdominance is another possibility whereby the heterozygote is less fit than either homozygote. 4. A recent study suggests that Charles Darwin and his wife, Emma both had substantial inbreeding in their family history, with an estimated average inbreeding coefficient of in their common ancestors. To make matters worse, Charles and Emma were themselves first cousins. a. Estimate their kinship coefficient (15 points). (avg. score 12.95) Where individuals 8 and 6 are Charles and Emma and 10 is their hypothetical offspring Chains: 8-3-CA1-4-6 (5 links) 8-3-CA2-4-6 (5 links)!! f 10 1 $ ## & "" 2 % 5! + 1 $ # & " 2 % 5 $ & % ( ) b. What is the probability that one of Charles and Emma s children would be homozygous for an allele that is identical by descent at a randomly-chosen locus? (5 points) (avg. score 3.0) ***************** , from the definition of the inbreeding coefficient f.

7 *****PLEASE READ THIS***** Part Three. Short answer. Undergrads, answer any 3 (8 points each). Grads, answer any 4 (6 points each). 5. What causes inbreeding depression? (answers 10, avg. 6.2 pts) There are two primary theories for the cause of inbreeding depression. The first, commonly called the Dominance Theory posits that inbreeding depression results due to the combined effects of homozygous deleterious recessive alleles, which increase as inbreeding proceeds. An alternative theory, known as Overdominance posits that there is an inherent advantage to being heterozygous at some loci, and that this advantage disappears as homozygosity increases under inbreeding. A complicating factor for overdominance is it is difficult to differentiate the effects of tightly linked deleterious alleles in trans-configuration, a phenomenon known as associative overdominance. Most modern theories favor some form of dominance as the primary explanation. Why does the extent of inbreeding depression vary among different species? Different species have different inherent levels of historical inbreeding due to variation in life history and breeding systems. In species with a long history of inbreeding, most deleterious alleles have already been purged by selection, so inbreeding depression tends to be less severe. There is also variation due to the specifics of population structure, historical effective population size, and selection regimes. But these are much less generalizable than the purging effect. 6. Why were many geneticists surprised at the levels of genetic variation revealed by allozyme loci 40 years ago? (answers 9, avg. 5.6 pts)*************** Based on theoretical expectations about the predominance of directional selection and the rarity of beneficial mutations, it was expected that there would be extremely low variation in proteincoding loci. It was expected that even slightly deleterious mutations, when spread across the genome, would cause an intolerable decline in fitness and species extinction in short order. The neutrality of many nonsynonymous mutations in protein-coding genes was not widely appreciated or understood.

8 7. What determines the equilibrium allele frequency in a population with a mixed mating system (selfing and outcrossing), assuming all Hardy-Weinberg assumptions are met except random mating? (answers 12, avg. 5.9 pts)******************* Allele frequencies do not change with inbreeding, only genotype frequencies. So the equilibrium allele frequency under these conditions is the starting allele frequency. 8. Compare and contrast the theories of inheritance proposed by Lamarck and Darwin? (answers 10, avg. 7 pts) Lamarck proposed that a complexifying force drove organisms to ever higher levels of complexity. He further hypothesized that use and disuse of organs affected their development and inheritance. Darwin s theory of inheritance (pangenesis) was in some ways similar to that of Lamarck in that he proposed that the reproductive materials consisted of gemmules that circulate through the system and are produced in proportion to use of different organs, accumulating in repoductive organs. In this sense the theory was Lamarckian in that it posited that characteristics acquired during the lifetime of an organism could be passed on to offspring.

9 9. Explain why most population geneticists prefer to work with codominant genetic markers rather than dominant markers. (answers 13, avg. 6 pts)**************** Codominant markers provide much more power than dominant markers. First of all, because allele frequencies of dominant markers must be estimated from the frequency of homozygous recessive genotypes, the standard error of these estimates is much higher (compare, for example problems 2.2C and 2.3B). Second, because one must invoke Hardy-Weinberg to estimate allele frequencies for dominant markers, these cannot be used to determine whether there are deviations from Hardy-Weinberg. Finally, because it is often advantageous to follow both chromosomes in a diploid organism, highly polymorphic dominant markers are at a premium. 10. Which type of selection would result in a higher equilibrium allele frequency for the allele with lower marginal fitness: a. underdominance or b. directional (purifying) selection? Feel free to define your conditions as you see fit. You always have the option of using software to help answer this question. (answers 3, avg. 6.7 pts) The answer to this question depends entirely on the conditions specified. If the starting allele frequency is below the equilibrium point in the underdominant system, the allele with lower marginal fitness will decline in frequency until it approaches 0, just as is expected with directonal selection. In contrast. If the allele frequency starts higher than the equilibrium point, the allele will progress to fixation, and therefore underdominance will result in a higher freqency of the allele with lower marginal fitness. Finally, if the allele frequency starts right at the equilibrium point, the system will stay there (assuming no other perturbations) and the allele frequency will be higher under the underdominance situation.