lecture26 - Lecture 26 In this lecture we will consider how...

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Unformatted text preview: Lecture 26 In this lecture we will consider how allele frequencies can change under the influence of mutation and selection. The first consider the conversion of a wild type gene to an altered allele by mutation: µ A → a µ = mutation rate (probability of a mutation/generation) Δ q mut = µ ƒ( A ) = µ p ≈ µ Typical mutation rates vary from µ = 10-4 — 10-8 Thus, in the absence of any other effects, such as selection, for any given gene the frequency of mutant alleles will increase a little each generation because of new mutations Consider the disease phenylketonuria (PKU), which is an autosomal recessive defect in the enzyme phenylalanine hydroxylase. The absence of the enzyme prevents phenylalanine from being metabolized causing unusually high levels of phenylalanine in the body leading to severe mental retardation. Say, that for PKU, µ = 10-4 . The frequency of PKU will then slowly increase each generation. When the allele frequency gets high enough selection against homozygotes will counterbalance new mutations and q will stay constant. In order to treat selection quantitatively we need an additional concept. S = selective disadvantage; and fitness = 1–S If a genotype has S = 0.75 then fitness = 0.25, meaning that individuals with this genotype will reproduce at a rate of only 25% relative to an average individual. Fitness can be thought of as a combination of survival and fertility. Recall that for alleles in H-W equilibrium (random mating) the genotype frequencies will be: ƒ( A / A ) = p 2 , ƒ( A / a ) = 2 pq , ƒ( a / a ) = q 2 Genotype frequency after selection Δ frequency A/A p 2 p 2 A/a 2 pq 2 pq a/a q 2 q 2 (1 – S) –S q 2 # q sel = –S q 2 In the steady state: # q sel + # q mut = 0, –S q 2 + µ = 0, µ = S q 2 q = . µ / S For PKU, q is 10-2 Sand during human evolution S ≈ 1. Therefore, the estimated value of µ is about 10-4 . The actual mutation frequency is probably not this high – and the relatively high q for PKU is probably due to a founder effect in the...
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This note was uploaded on 09/03/2009 for the course BIOL 7.03 taught by Professor Chriskaiser during the Fall '04 term at MIT.

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lecture26 - Lecture 26 In this lecture we will consider how...

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