Epistasis (Multiple Loci)

Question 1

how do continuous traits form?

Answer 1

many loci, small allelic effects- the more alleles involved the mot bell shaped the distribution of phenotypes is

Question 2

how many genotypes can be produced from a model with two biallelic loci?

Answer 2

9 (16 with doubles)

Question 3

how does additive gene action contribute to dihybrid crosses in terms of fitness?

Answer 3

the presence of each allele contributes to the fitness of the organism by an amount that is relative to the contributions of the other allele. so that AA is 1+s and BB is 1+t so AABB has a fitness of 1+s+t and AaBB has a fitness of 1+s/2+t

Question 4

what does the plane of fitness look like when there is additive gene action between two loci which each have 2 alleles?

Answer 4

a diagonal plane increasing upwards from aabb to AABB

Question 5

what is a fitness plane?

Answer 5

it shows how the fitness increases when a genotype is changed by one allele

Question 6

what does the fitness landscape look like when there is additive gene action between two loci which each have 2 alleles for a haploid individual?

Answer 6

a diagonal plane increasing upwards from ab to AB

Question 7

what are the two possible ways in which the two alleles at two loci will interact and contribute to fitness?

Answer 7

they will either act in an additive way in which there is a selective advantage on combination of alleles and there is no interaction between loci (certain combinations contribute more to the fitness that others) (fitness landscape if diagonal straight) or the two loci can have epistatic interactions in which there are no addictive effects and the fitness effect of an allele depends on genetic background

Question 8

what is epistasis in term of multiple loci traits?

Answer 8

when the allelic effect on the fitness depends on its genetic background

Question 9

what are 4 types of epistasis?

Answer 9

• no epistasis, instead there is additive gene action
• magnitude epistasis- fitness increases but the extent of increase depends on the genetic background
• sign epistasis- the effect of a mutation or certain allele is either positive or negative depending on its background
• reciprocal sign epistasis- fitness valley- two populations are divided into two groups

Question 10

what is magnitude epistasis?

Answer 10

when two mutations both increase fitness but at different rates when together or separate. When the double mutation has a fitter phenotype than either single mutation is synergistic and when two mutations together have a smaller effect than expected from their effects when alone, it is called negative or antagonistic epistasis.

Question 11

when we talk about fitness landscapes and epistasis, what do we mean in terms of s?

Answer 11

when a mutation to the wild type increase s depending on its genetic background- with sign epistasis S is either increase of decreased depending on which allele is mutated from ab

Question 12

what are two types of magnitude epistasis?

Answer 12

synergistic (mutational effect increases with number of mutations) and antagonistic (mutation effect decreases with number of mutations)

Question 13

what is synergistic magnitude epistasis?

Answer 13

when the mutational effect on S increases as the number of mutations increases

Question 14

what is antagonistic magnitude epistasis?

Answer 14

when the mutational effect on S decreases as the number of mutations increases

Question 15

how can the shape of the fitness landscape constrain the evolutionary trajectory?

Answer 15

when there is no epistasis and just additive then the evolutionary trajectory can take either path a s increase equally irrespective or a or b changing.
when there is sign epistasis then the evolutionary trajectory to constrained to one side of the path as a mutation within a certain genetic environment would be deleterious- mutations must occur in a certain order

Question 16

what is reciprocal sign epistasis?

Answer 16

when two deleterious genes increase fitness when together e.g producing a toxin alone can kill a bacterium, and producing a toxin exporter alone can waste energy, but producing both can improve fitness by killing competing organisms

Question 17

what is sign epistasis?

Answer 17

• when is either beneficial or deleterious depending on its genetic environment.
• occurs when one mutation has the opposite effect when in the presence of another mutation. This occurs when a mutation that is deleterious on its own can enhance the effect of a particular beneficial mutation.

Question 18

when e talk about the types of epistasis what type of organisms are we referring to?

Answer 18

diploid when talking about additive (but can also talk about haploid) and haploid when we are talking about magnitudal, sign or reciprocal sign

Question 19

how can the shape of the fitness landscape constrain the evolutionary trajectory?

Answer 19

because evolution is deterministic, only mutations that are beneficial will be maintained in a population. so in order for a combination of mutations to be selected for in a population, the path that was taken to obtain them must have been beneficial.
when there is no epistasis and just additive then the evolutionary trajectory can take either path a s increase equally irrespective or a or b changing.
when there is sign epistasis then the evolutionary trajectory to constrained to one side of the path as a mutation within a certain genetic environment would be deleterious- mutations must occur in a certain order

Question 20

what is an example of the using the fitness landscape to predict the evolutionary trajectory?

Answer 20

E.coli’s resistance to penicillin- 5 mutations are needed to efficiently break down the Beta- lactic ring- you can look at the likelihood of the trajectories from one mutations occurring in addition to another in order to discover the chain of mutational events - how pTEM wild type turns into pTEM*

Question 21

describe the experiment used to discover the evolutionary trajectory of pTEM to pTEM*

Answer 21

• pTEM* contains 5 mutations (4 in extrons and 1 in introns)
• we want to know how this mutant evolves (what is the sequence of mutations that occur and how epistasis constrained the evolution)
• when we look at the fitness landscapes, we see that if there is no epistasis (additive) then the evolutionary trajectory from one mutation to another can occur in either way. we see that if sign epistasis occurs then there is only one possible trajectory and if there is reciprocal sign epistasis then the evolutionary trajectory is blocked.
• there are 5 mutations and therefore 120 possible trajectories
• the probability of TEM becoming TEM* is the same as the sum of the probabilities of each mutation occurring independently

Question 22

describe the experiment used to discover the evolutionary trajectory of pTEM to pTEM*

Answer 22

• pTEM* contains 5 mutations (4 in extrons and 1 in introns)
• we want to know how this mutant evolves (what is the sequence of mutations that occur and how epistasis constrained the evolution)
• when we look at the fitness landscapes, we see that if there is no epistasis (additive) then the evolutionary trajectory from one mutation to another can occur in either way. we see that if sign epistasis occurs then there is only one possible trajectory and if there is reciprocal sign epistasis then the evolutionary trajectory is blocked.
• there are 5 mutations and therefore 120 possible trajectories
• the probability of TEM becoming TEM* is the same as the sum of the probabilities of each mutation occurring independently
• you induce mutations in populations of e coli and look at the probability of each mutation becoming fixed in the population relative to the probability of the others becoming fixed- the highest probability if the path
• the probability of fixation for each mutation will be dependent on whether it is deleterious of beneficial in the presence of other mutations (what type of epistasis is acting on it)

Question 23

how performed the evolutionary trajectory pTEM study?

Answer 23

Dan Weinreich

Question 24

what is the name of the e.coli resistant strain?

Answer 24

pTEM*