Molecular evolution Flashcards
How to compare AA sequences
see number of different AA between two species homologous sequences / tot AA in that sequence
Also can make phylogenetic tree by AA substitutions to see divergent time between species
Example of comparison of AA sequences
Hb alpha chain
human to horse, 18 different sites
human to shark, 79 different sites.
make a matrix
what did Linus Pauling find?
2 time Nobel prize winner
1962 - linear relationship between genomes and time since divergence, estimated from fossil record - molecular clock hypothesis
molecular clock hypothesis
rate of evolutionary change of any specified protein was approximately constant over time and over different lineages
what does evolutionary rate equal?
rate of nucleotide substitutions
how to calculate nucleotide substitution rate
r=K/2T
no. substitutions per site per year = evolutionary distance between 2 sequences/2x time of divergence between two sequences.
a simple (parsimonious) process is assumed(each nt changed only once)
how to find evolutionary distance?
P proportion of NT which have changed
define synonymous and non synonymous substitution
synonymous - a substitution which can give the same AA. likely to occur. possible since some AA are degenerate.
Non synonymous subs are unlikely to occur because they cause a biological change in the organism
what is the Ka/Ks ratio
Ks = synonymous sub rate Ka = non syn sub rate. not likely/likely usually <1 rarely>1
how do you know if positive selection has occurred
Ka/Ks>1
example of genes positively selected for
immune system genes
what does population genetics study
change of allele frequencies of population over time
who came up with the neutral theory of molecular evolution?
motoo kimura 1968
very high rate of NT substitutions must mean that most mutations are neutral in NS, and caused by random drift go alleles that are selectively neutral.
Darwinian - survival of the fittest
Kimurian - survival of the luckiest
why may some regions of genes show less substitution than others?
functional constraint
eg Hb - c chain shows higher substitution rate than other domains, because it is a non functional region
what is the opposite of random mating
assortative mating
examples of genes with high functional constraint
Hb
histones
what is an OTU
operational taxonomic unit
level of taxonomic separation used
how to calculate p distance
what is it
Number of mis-matched sites/total no. sites
Simplest estimate of evolutionary distance.
length of branches in an evolutionary tree fits the p distance of OTU pairs