week 6- rates patterns Flashcards
why study rates of evolution
-key in molecular evolution how fast DNA sequences evolve
-rates amoung different genetic (codons) and nongeneic regions differ
-understand evolutionary forces responsible for variable rates and patterns of evolution. = functional constraint, positive selection, mutation input
what is the rate of point mutation
ultimate source of novelty
number of new sequence variants in a target sequence per unit time
what is a target sequence
nucleotide, gene, chromosome, genome
what is unit time
replication, generations, chronological time
why is rate of point mutation difficult to measure
mutations are unpredictable and often deleterious and lethal
how to calculate rate of mutations of the deleterious alleles
if you know frequency of mutant and the selection coefficient against that mutant then you can calculate this
q=u/s
q= frequency, u is mutation rate, and s is selection coefficient
what does neutral mutation rate equal and how to work out
substitution for neutral alleles
use non-functional DNA and homologous DNA sequences between two species with known divergence time (e.g. from fossils) and generation times
human and chimpanzee: non-genic regions
2x10-8 per nucleotide per generation
multiplying this with human genome size of 7x109:
100 new point mutations per baby
explain the direct method
compare non-recombining DNA of two individuals with known generations apart
Rates vary across the genome
what is rate of substitution
how long does it take for all individuals of a species to have that particular mutation
equation for rate of nucleotide substitution
r = K/2T
r is number of substitutions per site per year
K is number of substitutions betwween two sequences
T is time of divergence
what is a non-synonymous rate
approx. 300 fold diffference between genes
-very conservative: core histones H3 and H4: practically zero
-interferon y: 3.1x 10-9 years
what is a synonomous rate
varies across gene but much smaller standard variation
-logical that synonomous substitutions are more frequent as those substitutions do not lead to a different amino acid in the protein, hence less/no purifying selection
is synonymous or non-synonymous faster rate of evolution
synonymous about 5 times faster
relative rate of evolution letters explained
-dN is number of non-synonymous substitutions per non-synonymous site
-dS is number of synonymous substitutions per synonymous site
-dN/dS ratio also called lower case omega (interchangeable with KA/KS)
what is directional pattern
we know which one is the original e.g. A->T
what is nondirectinal
we do not know which direction e.g. A <-> T
how to work out direction of mutation
need to use an outgroup to know direction, use a pseudogene as compared to its functional counterpart
how many possible changes
12 possible changes: matrix: relative frequency in which a change occurs
what are substitution matrices used for
to calculate distances between sequences and build phylogenetic trees
what can different models of substitution rates be used fir
can be used when building a phylogeny to understand which substitutions are more likely
what are all synonymous mutations
assumed to be selectively neutral
what can nonsynonymous mutations be
advantageous, neutral or disadvantageous, suggestive of selection
what do nonsynonymous nutations that are advantageous undergo
undergo fixation faster than neutral
if dN/dS >1
positive selection
if dN/dS = 1
strictly neutral (is it a functional gene)
if dN/dS <1
only drift and negative or purifying selection act
what does high dN =
positive selection
what does low dN =
purifying selection
is positive selection or purifying selection common
purifying
positive is rare
how to calculate dN/dS
need 2 DNA sequences so you can identify mutant sites
-ancestral sequence or outgroup
need to translate into amino acids to see if mutation in the codons lead to a different a.a.
need to determine how many sites could be synonymous or non-synonymous if they mutated
then calculate dN as number of nonsynonymous mutations/total nonsynonymous sites and dS accordingly
What is the molecular clock
the hypothesis that DNA sequences accumulate changes at a constant rate through time
provides a simple yet powerful way of dating evolutionary events
as a result opf the molecular clock what is the number of differences in a DNA sequence between two organisms proportional to
the time since divergence
why is the molecular clock called that
although substitutions occur at random times the rate at which they occur is assumed to be constant or ‘clocklike’ through time and across lineages
what does the molecular clock allow you to calculate
divergence times for other species
molecular clock controversy
the clock is ‘sloppy’ woth variable ‘tick rate’
The result is large confidence intervals on date estimates
explain mitochondrial DNA rates
Mt coding genes much higher synonymous rates than nucler coding DNA
rate of mutation higher
because Mt rate of mutation is higher what does that mean
low fidelity of replication, inefficient repair, high concentration of mutagens, effective population size 1/4 of that of nuclear genes
in plants and fungi at what rate do Mt evolve
very slowly but with some exceptional taxa
explain chloroplast DNA evolution
150000 bp long (50 -250 kb)
conserved in gene order and content
in photosynthetic plants: dN/dS<1
in non-photosynthetic plants (parasites): dN/dS > 1
explain virus evolution
evolve extremely fast (1 million times faster than animal DNA)
serially sample viruses can be studied easily
KA/KS< 1, but purifying selection is weaker than in animal genes
errors in reverse transcription RNa to DNA
rapid rate changes properties, such as antigenicity
high error rate is actually an advantage: evolution of evolvability
what is coalescence
theory that allows estimation of population size in the past
looks for most common ancestor (MRCA)
how fast this goes is effected by population size, drift, selection, migration etc
relationship of all alleles: gene genealogy (or coalescent)
what do retrospective models of population genetics show
trace all alleles of a gene in a population to a single ancestral copy
what is coalescent theory a model of
how alleles sampled from a population may have originated from a common ancestor
what is the rate of coalescence impacted by
effective population size , mutation rate, other evolutionary processes
what is MSMC analysis
multiple sequenctially markocian coalescent.
could be used to estimate the demographic history of a population using whole genome sequences and coalescnet theory
