BIOL336-Midterm-2022W1Key

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University of British Columbia *

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336

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Biology

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Apr 3, 2024

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Given name FAMILY NAME (CAPS) Student Number: _____________________________ 1 Q1. (5 marks) Consider a new antibiotic that targets a particular site in the cell membrane. Before the antibiotic is used, mutations at that site that lead to antibiotic resistance will pre- exist at mutation-selection balance. If the mutation rate at that site is 10 -7 per generation and the selection coefficient against the resistant allele before antibiotic appears is 0.002, at what frequency do you expect the resistant allele to be present before the antibiotic is introduced? [Include the formula, show your work, and circle your final answer. Write the answer to five decimal places, e.g., 0.00011.] q = u/s q = 10^-7/0.002 q = 0.00005 è 2 pts for formula, +2 pts for plugging in numbers correctly, +1 for final calculation Q2. (5 marks) In a hospital where a single patient is infected with the resistant bacteria, what is the probability that that resistant allele is lost despite the fact that the mutation increases the ability of the bacteria to survive and transmit to another patient by 30% (i.e., s = 0.3). [Include the formula, show your work, and circle your final answer. Write the answer to one decimal places, e.g., 0.1, and assume that the population is large.] Prob fix = 2s =2(0.3) = 0.6 Prob loss = 1-Prob fix = 0.4 [Unlikely, but might also use Kimura’s formula: Prob fix = (1-exp[-2s])/(1-exp[-2sN]), in a large population = (1-exp[-2s]) = 0.45, for a prob of loss of 0.55. Answers are different because selection is so strong.] è 2 pts for formula, +2 pts for plugging in numbers correctly, +1 for final calculation

2 Q3. (3 marks) Many antibiotic resistance genes are carried by plasmids, which are small circular genetic elements that can be transferred from bacterium to bacterium (Figure). Relative to genes in the main chromosomal genome, plasmids allow for [choose the best answer] : □ selection X recombination □ disequilibrium □ hitchhiking □ epistasis Q4. (5 marks) When antibiotic resistance first appears, how many generations would it take for resistance to rise from an initial frequency of 10 -6 infections to a frequency of 50% if it increases the chance that an infection survives and transmits by s = 0.3. [Include the formula, show your work, and circle your final answer for t in generations. Write the answer to five decimal places, e.g., 0.00011. Hint: it can be easier to work with ࠵?[࠵?]/࠵?[࠵?] ] ࠵?[ ࠵?] ࠵? [࠵?] = ࠵? ! " ࠵? # " ࠵?[ 0] ࠵? [0] 0 .5 0 .5 = 1 .3 " 1 10 $% 1 − 10 $% 1 − 10 $% 10 $% = 1 .3 " è Logging both sides and solving for t: t =52.7 [Accept close solutions] Alternatively, could use the other formula: ࠵?[ ࠵?] = & ! " ([ *] & ! " ([ *] , & # " - [*. p[0]=10^-6 q[0] = 1-10^-6 = 0.999999 wA = 1.3 wa = 1 p[t] = WA^t p[0]/ WA^t p[0]+ Wa^t q[0] 0.5 = 1.3^t 10^-6 / 1.3^t 10^-6 + 0.999999 Can solve for t or estimate (t ~ 52) è 2 pts for formula, +2 pts for plugging in numbers correctly, +1 for final calculation 2. 3. Relaxasome Transferasome DNA polymerase F plasmid F plasmid 4. Old donor New donor Chromosomal DNA F plasmid Chromosomal DNA Donor Recipient 1. Pilus Pilus Pilus By Adenosine - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=783186 4

3 Q5. (3 marks) The form of selection in the previous question Q4 is □ Dominant selection favouring resistance □ Additive selection favouring resistance □ Heterozygote advantage X Directional selection favouring resistance Q6. (3 marks) Which historical figure might have said that the frequency of antibiotic resistance rises because cells exposed to antibiotics practice eliminating the antibiotics and pass on this enhanced performance to their daughter cells? □ Carolus Linneaus X Jean Baptiste-Lamarck □ Thomas Malthus □ Charles Lyell

4 Q7. The abstract of “Adaptation to the fitness costs of antibiotic resistance in Escherichia coli ” by Schrag et al. (1997) in Proc. R. Soc. B 264:1287 reads [=with some wording help]: “Policies aimed at alleviating [=fixing] the growing problem of drug-resistant pathogens by restricting antimicrobial usage implicitly assume that resistance reduces the Darwinian fitness of pathogens in the absence of drugs. While fitness costs have been demonstrated for bacteria and viruses resistant to some chemotherapeutic agents [=drugs] , these costs are anticipated to decline during subsequent evolution. This has recently been observed in pathogens as diverse as HIV and Escherichia coli . Here we present evidence that these genetic adaptations to the costs of resistance can virtually preclude resistant lineages from reverting to sensitivity [=adaptations that lessen the cost of resistance can prevent the spread of mutations that eliminate resistance] . We show that second site mutations [=at other genomic positions] which compensate for the substantial (14 and 18%* per generation) fitness costs of streptomycin resistant ( rpsL ) mutations in E. coli create a genetic background in which streptomycin- sensitive, rpsL + alleles have a 4-30%* per generation selective disadvantage relative to adapted, resistant strains. We also present evidence that similar compensatory mutations have been fixed in long-term streptomycin-resistant laboratory strains of E. coli and may account for the persistence of rpsL streptomycin resistance in populations maintained for more than 10 000 generations in the absence of the antibiotic. We discuss the public health implications of these and other experimental results that question whether the more prudent use of antimicrobial chemotherapy will lead to declines in the incidence of drug-resistant pathogenic microbes.” A. (4 marks) The main message of this abstract is that [choose the best answer] : □ antibiotic resistance disappears rapidly in the absence of the antibiotic X evolution can lead to the reduction of fitness costs of antibiotic resistance □ antibiotic resistance is likely to evolve □ second site mutations can occur □ the dollar costs of antibiotic resistance decline over time B. (6 marks) Their Figure 2 is illustrated on the right (CAB281 refers to the wildtype E. coli bacteria used in their experiments). The two bottom axes refer to streptomycin resistant ( Str R ) and sensitive ( Str S ) strains, with or without the compensatory second-site mutation. In the abstract, the phrase “substantial (14 and 18%* per generation) fitness costs of streptomycin resistant ( rpsL ) mutations” is referring to the heights of which bars: X STR1 relative to CAB281 □ STR1 relative to STR12 □ STR12tr relative to STR12 □ STR12tr relative to CAB281 In the abstract, the phrase “streptomycin-sensitive, rpsL + alleles have a 4-30%* per generation selective disadvantage relative to adapted, resistant strains” is referring to the height of: □ STR1 relative to CAB281 □ STR1 relative to STR12 X STR12tr relative to STR12 □ STR12tr relative to CAB281 [*Ignore this variation in costs, which was due to having different resistance mutations.]

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