W1 L3 molecular clock Th Flashcards
What is the molecular clock
Assesses AA change rather than nucleotide change
Reading the molcular clock
- May be used to form e.g. an ultrametric tree or plot e.g. α-globin protein divergence
λ = rate of AA change = substitutions per AA site per unit time = (total substitutions/length of protein)/total T.
Comparing the divergence of two protein
λ = K/2T
K = -ln(1-D) D is divergence which will always be underestimated charge if the is multiple hit and parallel changes
Proteins have 20 AA sites = K (no. changes) related to D. Slope of 1 & then plateaus.
What is our assumption in amino acid changes
we assume all AA replacements happen with equal likelihood. This is not true
AA change depends on: (may involve many nt changes) & functional equivalence of AA
Dayhoff Matrices: Likelihood each type of AA replacements are derived empirically from data (matrix) of closely related seq
What do we need to do to calculate the molecular clock?
*Align multiple sequences
*Calculate D for each pair of sequences (perhaps using a substitution matrix to correct for types)
*Estimate K to correct for multiple substitutions
*Estimate T from the fossil record
Plot K (replacement rate) vs T
Different shape of amino acid change reason
Different proteins have different substitution rate as Proteins with different functional constraints
But the rate itself is constant
Each protein have their own clock
Kimura and Ohta On molecular clock
- different proteins evolve at different rates because they have different proportions of deleterious mutations (“selective constraint differs”). so each protein keeps to a (its own) clock
- Because most amino acid substitutions are neutral (remember substitution = divergence between species)
- And differing ‘selective constraint’ means the number of possible neutral mutations differs between proteins
Fixation rate If protein are adaptive
f =2Nµa X Pr(fix)
= 2Nµa X ~2s
=4Nµas = mutation rate, population size & selective constraint.
Why is adaptive protein affect fixation rates so much
Kimura argued that it is unlikely that the product of population size, advantageous mutation rate and selective co-efficient would be constant over the phylogeny of species
Phylogenetic trees reveal rate changes in Drosophila ADH
Branch lengths ∝ distance (phylogram).
* Length of D. miranda to D. persi vs. clade of D. ambigua to D. melanogaster (longer branch lengths).
* ∴ Clock does not apply here: differential change over same length of time => NOT all proteins evolve clock-like.
* Given stochasticity in neutral model, expect variance may/not be consistent with the molecular clock.
For a given data set we can ask: Is the observed rate difference significant
Calculating the average of phylogeny
Causes of Rate Variation: Rejection of Molecular Clock
Gene effects: Functional constraint, mutation rate heterogeneity: identify non-neutral evolution.
Taxon, lineage effect: Differences in generation time, repair efficiencies, metabolic rate, population size
Residue effect (combination): Variance model is wrong
