GENE30001 Lecture Notes - Lecture 2: Mutation Rate, Pypy, Pseudogene
14 Jun 2018
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Definitions:
Polymorphisms:
Human genetics >1% (SNPs vs SNV) frequency is too high to be explained by mutation alone
Neutralist theory: Most molecular variation that is fixed is neutral - so evolution is
governed by drift.
This means that there was a gene from a mutation and had some function and may have
disappeared via negative/purifying selection or favoured in positive. Neutralists say
regardless, it's neutral.
However they do allow for deleterious &advantageous mutations
The neutral model is the neutralist theory - loss by neg selection and replication with drift
and probability of fixation (1 / 2N )
Negative Selection/ Purifying Selection / Selective Constraint
Textbook: Coding sequences give abundant evidence that most mutations that change
amino acids are deleterious. By chance they may persist in a population for
a few generations, but eventually they are eliminated by selection; in this context
the process is called purifying selection
Selectionist Theory: There differences between species and much of the variation within
species is due to adaptive evolution.
W/i is a variant that is adaptive and maintained by balancing selection.
Calculate the mutation rate:
Look at the divergence of neutral sites between species.
1.
We need neutral loci, they can include 4 fold sites, also pseudogenes
2.
Fixation rate = mutation rate
However this method underestimates the number of changes as time goes more mutations
willer and a greater proportion of sites will be changed more than once.
Jukes and Cantor: If all based changes occurs at an equal frequencies.
Idea- b/c there are only 4 bases align with 25% chance that it's one of the bases .
Saturation leads to divergence.
Assumes all changes are equally likely BUT not all nucleotides change as the same rates.
There's difference between rates of transitions (pu-pu py-py) and transversions (pu-py) This
is shown in "Kimuras 2-parameter model"
Other mutations such as CpG being methylated and 5-methyl cytosine deanimated to
thymidine. => C-T occurs at a higher rate
How long will it take to lose half a pseudogene?
If mice diverged from us 65 myo in 2T it would show
60%
Gender based mutation:
Mutation rates in females < males
Autosomes = 1/2
-
X chromosomes = 2/3
-
Y chromosome = 0
-
Time s pent in female germline
Lecture 2 Mutations and Mutation Rates
Wednesday, 22 June 2016
10:51 AM
Lecture Notes 1- 12 Molecular Evolution and Population Genetics Page 1
Document Summary
Human genetics >1% (snps vs snv) frequency is too high to be explained by mutation alone. Neutralist theory: most molecular variation that is fixed is neutral - so evolution is governed by drift. This means that there was a gene from a mutation and had some function and may have disappeared via negative/purifying selection or favoured in positive. However they do allow for deleterious & advantageous mutations. The neutral model is the neutralist theory - loss by neg selection and replication with drift and probability of fixation (1 / 2n ) Textbook: coding sequences give abundant evidence that most mutations that change amino acids are deleterious. By chance they may persist in a population for a few generations, but eventually they are eliminated by selection; in this context the process is called purifying selection. Selectionist theory: there differences between species and much of the variation within species is due to adaptive evolution.
