Molecular evolution Flashcards by Jessica Menzies

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

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Example of comparison of AA sequences

Hb alpha chain
human to horse, 18 different sites
human to shark, 79 different sites.
make a matrix

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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

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molecular clock hypothesis

rate of evolutionary change of any specified protein was approximately constant over time and over different lineages

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what does evolutionary rate equal?

rate of nucleotide substitutions

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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)

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how to find evolutionary distance?

P proportion of NT which have changed

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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

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what is the Ka/Ks ratio

Ks = synonymous sub rate
Ka = non syn sub rate.
not likely/likely
usually <1
rarely>1

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how do you know if positive selection has occurred

Ka/Ks>1

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example of genes positively selected for

immune system genes

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what does population genetics study

change of allele frequencies of population over time

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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

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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

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what is the opposite of random mating

assortative mating

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examples of genes with high functional constraint

histones

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what is an OTU

operational taxonomic unit

level of taxonomic separation used

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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

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what is multiple substitution

when subs occurred multiple times at the same site.

how to calculate distance for AA sees considering multiple substitution

Poisson correction PC distance = -log(1-p)

kimuras distance = -log(1-p-0.2p^2)

what is Jukes Cantor model

JC model
model for distance estimation for nucleotides.
assumes equal distance of transversions and transitions. 1 parameter method.
D = -0.75

which are trasnversions and transitions?

TRANSITIONS
purine to purine = A-G,
pyrimidine to pyrimidine = C-T
TRANSVERSIONS
purine - pyrimidine

what is kimuras model for NT distance estimation

2 parameter method

transitions are more likely than transversions

who made the first phylogenetic tree

Ernst Haekel

``` define (for phylogenetic tree) root leaves branch length branch internal node ```

``` root - common ancestor leaves - current species branch length- time branch - relationship between species internal node - hypothesised ancestor ```

difference between rooted and unrooted tree

rooted tree needs an outgroup for a reference

what is a molecular phylogeny tree

Phylogenetic tree inferred by nucleotide sequences and/or amino acid sequences

ortholog meaning

sequences diverged due to speciation

paralog meaning

sequences diverged due to gene duplication

what is advantageous about molecular phylogeny tree?

no expertise of morphology needed | universal criteria

3 methods for constructing phylogenetic tree

1. distance methods - compute evolution distances for all OTUs and construct a tree which fits. 2. max parsimony method - choose tree which minimises no. changes required to explain data 3. max likelihood - choose tree which show highest likelihood for that evolution model.

what is UPGMA

unweighted pair group method with arithmetic mean distance between OTUs is an average uses sequential clustering algorithm. start with things most similar and build composite OTU. see slide 19 - make matrix of all sequences distance - in last column, do average of those seqs. - do average of the last column and next one - etc

weakness of UPGMA method

assumes evolutionary rates are the same among different lineages -> if the rates are different among the lineage, the tree is wrong. produces a rooted tree

what is the NJ method

neighbour joining most used method produced unrooted tree take into account averaged distances to other leaves (neighbor) as well

Maximum parsimony method

minimised no changes needed to explain data

how is tree root determined?

- between longest route between 2 OTUs - add data of reference gene or protein to original, reconstruct tree. root places in branch connecting reference and others. - use other biological evidence such as gene duplication

how to check reliability of phylo tree?

- use bootstrap confidence value - choose a random N number of sites - create pseudo alignment - make a phylogenetic tree of this pseudo alignment - repeat this step hundreds of times - count how many topologies support the original one - divide my total number of topologies made. - gives bootstrap value

steps in phylogenetic tree analysis

1. collect sequences 2. multiple sequence alignment 3. calculate distance 4. construction of NJ tree (use Clustalx) 5. expression of tree image (use NJ plot)

what is the purpose of phylogenetic tree analysis?

know the phylogenetic relationship of the species know the evolutionary background know the orthologous genes of the particular gene

3 outcomes of gene duplication

pseudogene - non-functionalisation modified function - sub-fudnctionalisation new function - neo-functionalisation

how are gene duplicates preserved?

by Neo-functionalization | gaining a new function

what is the 2R hypothesis?

vertebrates went through at least one (probably 2-round) whole genome duplications

how many genes are under positive selection?

5% of all gene families

what is molecular drive

operates independently of genetic drift and NS. gene conversion changes genetic composition changes due to certain genes replicating more, giving no biological advantage.

what is gene recruitment

a gene gets used for a new function in evolution. the gene has pleiotropic effect