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Org.Evolution

Molecular Evolution

Three questons of molecular evolution DNA/amino acid evolution; frequencies of neutral, deleterious, and adaptive mutations; evidence of natural selection from sequence data
Three steps to fixation of a gene new mutation, polymorphism, fixation
no change in fitness of a mutation neutral
decreasing fitness, or negatively selected deleterious
increasing fitness, or positively selected beneficial
an allele in generation "t" is randomly chosen to become the parental copy of an allele in the next generation Wright-Fisher model of reproduction
in a populaton with N = 5 and no mutation, each generation of allele is subject to extinction in the population genetic drift caused a randomly chosen allele in the first generation to be eventually fixed in the population later on
what acts on a population in the absence of mutation? genetic drift
give the equation for the rate of mutation that go to fixation over "t" generations k = 2Nup(fix)t2Nu=new mutationp(fix)=each mutation is fixed at this rate2Nup(fix)=number of mutations that go to fixaion per generation
If 2Nu=10-3, p(fix)=10-5, k=10-2, What is the probability that this site undergoes a substitution in 10^6 generations? What is the expected number of substitutions on a 10-kb long sequence? 0.01, solve for t-10^6, an k=10-2.....10-kb=10^4, so 10^4*0.01=100
In a population with infinite size, a new neutral mutation can reach fixation by genetic drift.T/F False. In any population with finite size (N), a new neutral mutation can reach fixation by genetic drift.
Can a neutral mutation reach fixation by genetic drift? Yes, in a finite population
Equation for fixation probability of a neutral mutation 1/(2N)
equation for the number of substitutions over "t" generation k = 2Nu(1/(2N))t = ut
if all mutations are neutral, then the substitution rate per generation (k/t) is.... the mutation rate
substitution of a neutral mutation will cause the substitution rate per generation to be... the mutation rate
probability of fixation is high if the mutation is ... positively selected
if mutations are (beneficial/deleterious), DNA sequences evolve much (slower/faster) than it would evolve under genetic drift beneficial; faster
beneficial mutations cause the substitution rate to be... higher
causes divergence between two sequences from two species base substitutions
give the equation for the expected divergenc if all mutations are neutral expected divergence = D = L*u*2tL=sequence lengthu=mutation rate per bp2t=divergence time
12 codons = __ amino acids 12 aa, 36bp
if a protein-coding sequenc has 12 codons, and 75% of mutations are nonsynonymous, the how many nonsynonymous and synonymous sites are there? 12 codons = 36 bp36*.75=27 non synonymous36*.25=9 synonymous sites
mutations that no dot change amino acid sequence neutral mutations
a mutation that is a functional change but no fitness change would be considered a _________ mutation neutral
a mutation that is little or none functional cange, change to an amino acid with similar propert, and change at functionally unimportant part of the protein is called neutral mutation
a mutation that is a functional chage and change in fitness is (2) deleterious and advantageous
how can you relate deleterious and advantageous and neutral mutatons? they all add up to 1f0(neutral) + f1(del) + f2(advantageous) = 1
name the polar, changed amino acids that are basic arginine, histidine, and lysine
what type of amino acid has electrically charged side chains that attract wate and oppositey charged ions polar, charged
name the polar, charged amino acids that are acidic aspartic acid, glutamic acid
name the polar, uncharged amino acids serince threonine, asparagine, glutamine, and tyrosine
what type of amino acid is uncharged with polar side chains that tend to form weak hydrogen bonds with water and with other polar or charged substances; mostly hydrophilic polar, uncharged
name the three amino acids with special cases glycine, proline, cysteine
name the non-polar amino acids alanine, phenylalanine, leucine, isoleucine, mehionine, tryptophan, and valine
in an ideal gene, if all mutations were neutral, non-synonymous sites would still be greater than synonymous sites. T/F False. they would be equal and diverge at the same rate
what happens in a population with only neutral and deleterious mutations, no beneficial nonsynonymous sites: Dn=Ln*f0*u*2t=Dn/Ln=2f0utsynonymous sites: Dc=2Lsut, ds=Ds/Ls=2utdn/ds=f0<1
if there are no beneficial mutations, then divergence at synonymous sites are __________; synonymous substitutions are determined by ____________; synonymous mutations are __________ similar; divergence time; neutral
if there is no beneficial mutations, then proteins constrained evolve slowly and nonsynonymous mutations are >>>> deleterious
proteins with relaxed constraint grow fast (insulin C)
if all types of mutatons occur in a population, then who goes to fixation? neutral and beneficial
if f2>0, dn/ds is eithr <1 or>1
if dn/ds>0 and f2>0 positive selection
what type of mutaton causes an amino acid change nonsynonymous
what type of mutation causes no amino acid change synonymous
there are two ways to get neutral mutations, what are they? synonymous mutation (no aa change) and nonsynonymous mutation (aa change) and fixation to genetic drift
fixation due to genetic drift is a _______ mutation neutral
no fixation from this mutation deleterious
fixation due to positive selection benefical mutation
three types of nonsynonymous mutations neutral, deleterious, beneficial
symbol for neutral mutation fo
symbol for deleterious mutation f1
symbol for beneficial mutation f2
how do you determine if there is evidence for positive selection? dn/ds>1, f2>0
two animals with a modified foregut ruminants, colobine monkey
number value on phylogenic tree branches is equal to dn/ds
the number of nonsynonymous substitutions are found by multiplying what by what? no. of fixed neutral mutations by no. fixed advantageous mutations
examination of within population variation gives what? f0 via polymorphism
how to determine the number of polymorphic sites? equals the number of mutation events on geneaology
Equation for expected number of polymorphic sites P = L*u*TT=sum of branch lengthsL=lenght of DNA sequenceu=neutral mutation rate
describe how to get the expected number of polymorphic sites =length of DNA sequence x neutral mutation rate x total branch length
why can ony neutral mutations be considered in genealogy? deleterious mutations are quickly removed by selection, cannot be included in sample sequences; advantageous mutations quickly go to fixation and cannot contribute to polymorphism
how to tell between synonymous and nonsynonymous sites? synonymous sites: P=L*u*Tnonsynonymouse sites: P=L*f0*u*T
if f2=0, then no advantageous mutation
if f2>0, dn/ds>pn/ps, then evidence of positive selection
how to test the significance between Dn/Ds and Pn/Ps? chi-square
what is the mcdonald-kreitman test? statistical test to determine adaptation, etc
examination of within population variation gives what? f0 via polymorphism
how to determine the number of polymorphic sites? equals the number of mutation events on geneaology
Equation for expected number of polymorphic sites P = L*u*TT=sum of branch lengthsL=lenght of DNA sequenceu=neutral mutation rate
describe how to get the expected number of polymorphic sites =length of DNA sequence x neutral mutation rate x total branch length
why can ony neutral mutations be considered in genealogy? deleterious mutations are quickly removed by selection, cannot be included in sample sequences; advantageous mutations quickly go to fixation and cannot contribute to polymorphism
how to tell between synonymous and nonsynonymous sites? synonymous sites: P=L*u*Tnonsynonymouse sites: P=L*f0*u*T
if f2=0, then no advantageous mutation
if f2>0, dn/ds>pn/ps, then evidence of positive selection
how to test the significance between Dn/Ds and Pn/Ps? chi-square
what is the mcdonald-kreitman test? statistical test to determine adaptation, etc
what is the most correct explanation of wy more antibiotics become ineffective in the treatment of bacterial infection mutations on bacterial genes that cause bacteria's resistance to drug become positively selected
what is an example of something that does not suppoert the hypothesis that teosinte is the proginator of maize? more sequence polymorphism is observed in the maize population than teosite population
describe selective sweep caused by a recent positive selection immediately after the fixation of an advantageous mutation, the amount of genetic variation around the mutation is greatly reduced
human like species in the past that are sister group of chimpanzees hominin
modern human evolution increased brain volume, early hominins found in africa
order of three modern humans homo erectus (1.6 mya) archaic homo sapiens (300 kya in africa and asia and europe) aka neanderthals; modern sapiens about 170 kya in africa, anatomically indistinguisable from today's humans
two hypothesis from origin of modern human multiregional hypothesis + replacement hypothesis
single wave of expansion by homo erectus, and continuity of descent to the present day multiregional hypothesis
asian and european populations of archais sapiens became extinct when modern sapiens expanded out of africa replacement (out of africa) hypothesis
mitochondrial eve supports out of affrica hypothesis, based on phylogeny of 53 individuals
there was only one woman at that time who became the ultimate ancestor of all humans misunderstanding of mitochondrial eve
the most recent common ancestor (MRCA) of mitochondrial DNAs of all humans was carried by a woman who is estimated to have existed about 140,000 years ago mitochondrial eve
two reasons mitochondrial eve is misunderstood genealogy for a given segment of DNA has to have one MRCA even though there were always a large number of individuals in the population (genetic drift); genealogies (phylogenies) for different loci are different: because of RECOMBINATION
one interpretation of mitochondrial eve is wrong because of recombination. explain gene lineages for different loci are independent with each other
genetic variation in humans DNA sequences from two randomly chosen human individuals are different from each other at 0.1% of nucleotide sites - lower than other mammalian species
two reasons for low genetic variation human population expanded only recently from small ancestral population (170,000 years ago), not all individuals contribute to reproduction equally (true for many other organisms)
reasons for low genetic variation include reasons for effective population sizes, census size
give reasons for the genetic evidence for rapid spread of Mongolian male line Y chromosome sequences from about 2000 men from major regions of Eurasia; highly polymorphic sequences; consistent with Genghis Khan; colonization-extinction events greatly reduce effective population size; similar Y sequence from one male 1000 years ago
colonization-extinction events greatly (increase/decrease) population size ang genetic diversity of population decrease
if there are few differences among different geographic populations in nuclear genes, what is different? allele frequencies are different between populations
is there recent divergence and continuation migration between populations? what does this lead to? yes, and it leads to genetic variation
is it rare or common to have nucleotide sites that are polymorphic with G and T nucleotides yes, rare, common that polymorphism is between G and T
if multiple genes contribute to skin pigmentation and there is normal polymorphism in africans, what is represented in low polymorphism with europeans? selective sweeps with low polymorphism in europeans
what is the 'hitchhiking' effect of beneficial mutations or 'selective sweep' sudden disappearance of polymorphism
when is selective sweep easily observed immediately after the fixation of a beneficial mutation, when local polymorphism just been wiped out
if new neutral mutations build up polymorphism and erase the signature of the sweep then, the fixation happened in a not-so-recent past
positive selection to reduce the risk of malaria G6PD
ectodysplasin pathway in development of hair glands, an amino acid substitution causing less hairs on skin rapdily went to fixation in asian populations EDAR gene
a gene showing a strong pattern of selective sweep lactase gene (LPH)
mutualism between a human population and a target plant and animal population domestication
seperate selective sweeps in European and African populations, cis-regulatory mutations that were positively selected Lactase (LPH) gene
normal function of this gene needed for speech FOXP2
significant of selective sweep, but weaker signal of selective sweep FOXP2
Created by: KarinWi