Molecular Evolution
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| Three questons of molecular evolution | DNA/amino acid evolution; frequencies of neutral, deleterious, and adaptive mutations; evidence of natural selection from sequence data
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| Three steps to fixation of a gene | new mutation, polymorphism, fixation
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| no change in fitness of a mutation | neutral
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| decreasing fitness, or negatively selected | deleterious
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| increasing fitness, or positively selected | beneficial
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| 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
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| 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
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| what acts on a population in the absence of mutation? | genetic drift
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| 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
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| 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
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| 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.
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| Can a neutral mutation reach fixation by genetic drift? | Yes, in a finite population
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| Equation for fixation probability of a neutral mutation | 1/(2N)
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| equation for the number of substitutions over "t" generation | k = 2Nu(1/(2N))t = ut
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| if all mutations are neutral, then the substitution rate per generation (k/t) is.... | the mutation rate
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| substitution of a neutral mutation will cause the substitution rate per generation to be... | the mutation rate
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| probability of fixation is high if the mutation is ... | positively selected
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| if mutations are (beneficial/deleterious), DNA sequences evolve much (slower/faster) than it would evolve under genetic drift | beneficial; faster
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| beneficial mutations cause the substitution rate to be... | higher
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| causes divergence between two sequences from two species | base substitutions
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| 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
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| 12 codons = __ amino acids | 12 aa, 36bp
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| 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
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| mutations that no dot change amino acid sequence | neutral mutations
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| a mutation that is a functional change but no fitness change would be considered a _________ mutation | neutral
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| 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
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| a mutation that is a functional chage and change in fitness is (2) | deleterious and advantageous
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| how can you relate deleterious and advantageous and neutral mutatons? | they all add up to 1f0(neutral) + f1(del) + f2(advantageous) = 1
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| name the polar, changed amino acids that are basic | arginine, histidine, and lysine
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| what type of amino acid has electrically charged side chains that attract wate and oppositey charged ions | polar, charged
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| name the polar, charged amino acids that are acidic | aspartic acid, glutamic acid
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| name the polar, uncharged amino acids | serince threonine, asparagine, glutamine, and tyrosine
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| 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
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| name the three amino acids with special cases | glycine, proline, cysteine
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| name the non-polar amino acids | alanine, phenylalanine, leucine, isoleucine, mehionine, tryptophan, and valine
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| 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
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| 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
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| if there are no beneficial mutations, then divergence at synonymous sites are __________; synonymous substitutions are determined by ____________; synonymous mutations are __________ | similar; divergence time; neutral
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| if there is no beneficial mutations, then proteins constrained evolve slowly and nonsynonymous mutations are >>>> | deleterious
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| proteins with relaxed constraint grow | fast (insulin C)
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| if all types of mutatons occur in a population, then who goes to fixation? | neutral and beneficial
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| if f2>0, dn/ds is | eithr <1 or>1
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| if dn/ds>0 and f2>0 | positive selection
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| what type of mutaton causes an amino acid change | nonsynonymous
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| what type of mutation causes no amino acid change | synonymous
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| 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
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| fixation due to genetic drift is a _______ mutation | neutral
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| no fixation from this mutation | deleterious
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| fixation due to positive selection | benefical mutation
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| three types of nonsynonymous mutations | neutral, deleterious, beneficial
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| symbol for neutral mutation | fo
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| symbol for deleterious mutation | f1
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| symbol for beneficial mutation | f2
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| how do you determine if there is evidence for positive selection? | dn/ds>1, f2>0
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| two animals with a modified foregut | ruminants, colobine monkey
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| number value on phylogenic tree branches is equal to | dn/ds
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| the number of nonsynonymous substitutions are found by multiplying what by what? | no. of fixed neutral mutations by no. fixed advantageous mutations
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| examination of within population variation gives what? | f0 via polymorphism
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| how to determine the number of polymorphic sites? | equals the number of mutation events on geneaology
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| Equation for expected number of polymorphic sites | P = L*u*TT=sum of branch lengthsL=lenght of DNA sequenceu=neutral mutation rate
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| describe how to get the expected number of polymorphic sites | =length of DNA sequence x neutral mutation rate x total branch length
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| 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
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| how to tell between synonymous and nonsynonymous sites? | synonymous sites: P=L*u*Tnonsynonymouse sites: P=L*f0*u*T
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| if f2=0, then | no advantageous mutation
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| if f2>0, dn/ds>pn/ps, then | evidence of positive selection
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| how to test the significance between Dn/Ds and Pn/Ps? | chi-square
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| what is the mcdonald-kreitman test? | statistical test to determine adaptation, etc
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| examination of within population variation gives what? | f0 via polymorphism
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| how to determine the number of polymorphic sites? | equals the number of mutation events on geneaology
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| Equation for expected number of polymorphic sites | P = L*u*TT=sum of branch lengthsL=lenght of DNA sequenceu=neutral mutation rate
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| describe how to get the expected number of polymorphic sites | =length of DNA sequence x neutral mutation rate x total branch length
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| 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
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| how to tell between synonymous and nonsynonymous sites? | synonymous sites: P=L*u*Tnonsynonymouse sites: P=L*f0*u*T
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| if f2=0, then | no advantageous mutation
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| if f2>0, dn/ds>pn/ps, then | evidence of positive selection
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| how to test the significance between Dn/Ds and Pn/Ps? | chi-square
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| what is the mcdonald-kreitman test? | statistical test to determine adaptation, etc
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| 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
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| 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
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| 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
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| human like species in the past that are sister group of chimpanzees | hominin
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| modern human evolution | increased brain volume, early hominins found in africa
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| 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
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| two hypothesis from origin of modern human | multiregional hypothesis + replacement hypothesis
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| single wave of expansion by homo erectus, and continuity of descent to the present day | multiregional hypothesis
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| asian and european populations of archais sapiens became extinct when modern sapiens expanded out of africa | replacement (out of africa) hypothesis
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| mitochondrial eve | supports out of affrica hypothesis, based on phylogeny of 53 individuals
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| there was only one woman at that time who became the ultimate ancestor of all humans | misunderstanding of mitochondrial eve
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| 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
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| 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
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| one interpretation of mitochondrial eve is wrong because of recombination. explain | gene lineages for different loci are independent with each other
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| 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
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| 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)
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| reasons for low genetic variation include reasons for | effective population sizes, census size
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| 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
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| colonization-extinction events greatly (increase/decrease) population size ang genetic diversity of population | decrease
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| if there are few differences among different geographic populations in nuclear genes, what is different? | allele frequencies are different between populations
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| is there recent divergence and continuation migration between populations? what does this lead to? | yes, and it leads to genetic variation
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| 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
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| 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
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| what is the 'hitchhiking' effect of beneficial mutations or 'selective sweep' | sudden disappearance of polymorphism
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| when is selective sweep easily observed | immediately after the fixation of a beneficial mutation, when local polymorphism just been wiped out
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| if new neutral mutations build up polymorphism and erase the signature of the sweep then, | the fixation happened in a not-so-recent past
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| positive selection to reduce the risk of malaria | G6PD
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| 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
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| a gene showing a strong pattern of selective sweep | lactase gene (LPH)
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| mutualism between a human population and a target plant and animal population | domestication
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| seperate selective sweeps in European and African populations, cis-regulatory mutations that were positively selected | Lactase (LPH) gene
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| normal function of this gene needed for speech | FOXP2
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| significant of selective sweep, but weaker signal of selective sweep | FOXP2
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