Topic 10 Neutral Theory and Molecular Population Genetics

Question 1

classical hypothesis

Answer 1

• predicted there would be very little genetic variation w/in and among populations
• little heterozygosity

Question 2

Balance hypothesis

Answer 2

• Predicted that Balancing selection would be predominant, and heterozygosity would be high
• Balancing sel’n: any form of sel’n that acts to maintain variation

Question 3

Classical vs. balance hypothesis

Answer 3

-balance hypothesis won

Question 4

Selectionists vs. Neutralists

Answer 4

1. Selectionionists: argued that selection is responsible for maintaining high genetic variations, -selection is largely responsible for the patterns observed w/in and among pop’s and species
2. Neutralists: argues that most of the variation is nature is neutral (does not affect fitness).
   - Most of the variations are due to the interactions b/w neutral mutations and genetic drift
   - due to drift randomly fixing neutral mutations

Question 5

susbstitution

Answer 5

• the replacement of one amino acid, or nucleotide for another in the entire populations (or species)
• this leads to fixed differences b/w pop’s or species

Question 6

polymorphism

Answer 6

the segregation of two or more variants (alleles) of a gene or protein in a pop’n or species
-when 2 or more variants or more clearly diff phenotypes exist in the same pop’n

Question 7

Molecular clock hypothesis

Answer 7

-a given gene or protein evolves at a constant rate

-

Question 8

Generation Time Hypothesis

Answer 8

• organisms with similar generation times have a molecular clock
• Wen Hsiung Li demonstrated this
• organisms with small gen. time have a high mutations’year, and vice versa
• but if you look at organisms with similar gen time, there is a molecular clock

Question 9

Metabolic Rate Hypothesis

Answer 9

• suggested that organisms with higher metabolic rates will have higher mutations rate (due to mutagenic effect of radicals from aerobic respiration)
• Problem: metabolic rate correlate w/ gen times and difficult to separate the effects of each

Question 10

Neutral Theory and Heterozygosity

Answer 10

• Neutral theory predicts that heterozygosity increases as a function of pop’n size
• why: F^= 1/ (4Ne*u +1) and H^= 1 - F^

Question 11

which organism/bacteria exhibits latitudinal cline

Answer 11

• drosophila melanogaster exhibits a latitudinal cline in the ADH locus
• proved neutralists wrong: they argued that there should be no env. correlations among loci

Question 12

Functional constraints

Answer 12

• a very important DNA region will evolve very slowly
• e.g. catalytic site (i.e. CO1 rxn site, histones)

-Neutral theory predicts that diff DNA regions evolve at diff rates based on fxnal constraints

Question 13

Pseudogenes

Answer 13

• type of functional constraint
• nonfunctional genes which evolve very rapidly
• arise by gene duplications and lose their fxn
• actually happens this way

Question 14

Genetic code degeneracy

Answer 14

• genetic code is degenerate; neutral theory predicts:
  1. 4-fold degenerate sites will evolve more quickly than 2-fold degenerate sites
  2. third codon pos’n will evolve more quickly than first pos’n sites. Second codon pos’n sites will evolve the slowest

Question 15

codon bias

Answer 15

• codon usage is highly non-random. This is why all synonymous mut’ns are not neutral, and diff codons for the same a.a. are not used equally
• genes expressed the most will have the strongest codon bias –>reason: if silent mut’n creates a codon who’s tRNA is rare
• codon bias is weak or non-existent in genes which are rarely expressed

Question 16

Nearly Neutral Theory

Answer 16

• based on premise that slightly deleterious mut’ns can drift to fixation (or to high frequencies)
• accounts for many inconsistencies w/ neutral theory
• also many cases where selection has been important

Question 17

Purifying Selection

Answer 17

• the removal of deleterious mutations

- since most mut’ns are deleterious, purifying sel’n is common

Question 18

Positive Selection

Answer 18

Selection for favourable mut’ns that increase fitness (responsible for adaptive evolution)

Question 19

Balancing selection

Answer 19

Any form of sel’n that acts to maintain two or more variables at a locus

• sometimes called diversifying sel’n
• ex: overdominance (heterozygote superiority), frequency dependent selection

Question 20

McDonald Kreitman Test: state the 4 variables it looks at

Answer 20

a/c= b/d –>w/in spp under the null hypothesis of neutrality

a) the number of fixed non-synonymous substitutions b/w 2 species
b) the number of polymorphic non-synonymous sites w/in the 2 species
c) the number of fixed synonymous sites b/w the 2 species
d) the number of polymorphic synonymous sites w/in 2 species

• This test requires DNA sequence data that represents the sequence diversity w/in two different species
• adequate sample size is critical
• note: polymorphic site: many codons vs. substitution which is one codon

Question 21

Maximum Likelihood Mehtods

Answer 21

• given a data set, maximum likelihood methods select a model that maximizes the prob. of observing the data
• computationally very intensive methods

Question 22

Neutral Molecular Markers

Answer 22

• important to use markers that are “neutral” (not under selection)
• otherwise, it will screw up the data

-must be non-coding e.g. microsatellites

Question 23

Coalescence

Answer 23

the merging of genealogical lineages as we trace them backward in time

-note: w/ small pop’n size (historically speaking), you see more rapid coalescence than historically speaking large pop’n size