Chapter 8
In a population of diploid individuals, there are 2N gene copies at any given locus. If this locus is evolving neutrally by drift, we can trace any two of these gene copies back to a common ancestral gene copy that occurred 2N generations ago, on average, and we can trace all of the present gene copies back to an ancestral copy that occurred an average of 4N generations ago. When we trace the ancestry on gene trees using this approach, we say that gene copies coalesce to their most recent common ancestor.
2N Drift 2N 4N Coalesce
Click on the ancestral gene copy to which present copies 1 and 2 coalesce in this gene tree.
2 - 3 down
Watch the animation and examine the figure to the right, which depicts a channel protein that must bind ATP in order to function properly. Which of the following statements best articulates the reason that sequence variation in this protein is consistent with the predictions of the neutral theory?
Conserved amino acids are more common in the most functionally important region of the protein
Based on the neutral theory of molecular evolution, what is true of the expected substitution rate (K) for neutral alleles?
It equals the neutral mutation rate
Cryptic molecular variation uncovered by enzyme electrophoresis in the 1960s stimulated development of the neutral theory because of which of the following reasons?
Levels of polymorphism were higher than would be expected if natural selection were the main driver of sequence evolution.
Drag each codon change to the correct box to indicate whether it represents a synonymous or nonsynonymous substitution.
Synonymous: AUU → AUA ACU → ACA UUG → CUG
What do biologists call a period during which a population shows a temporary decrease in population size?
population bottleneck
The graphs below depict fluctuations of the frequency of a neutral allele in populations of different sizes. Each line represents the A1 frequency throughout a 100-generation simulated trial run of the population. Place the graphs in order of increasing population size.
1. Diverging, blue line up 2. Wide and centered 3. Thinner and centered
Click on the gene copy to which all gene copies in the present population coalesce in this gene tree.
3 - 3 down
Drag each statement to the correct box to indicate whether or not it is a contention of the neutral theory of molecular evolution.
Contention of the Neutral Theory: Most evolutionary substitutions that persist long enough to be measured in a population are neutral. Most of the genetic variation that persists long enough to be measured in a population is neutral.
Sometimes the observed heterozygosity of a large population resembles what we would expect in a small population subject to strong genetic drift. These large populations often have a history of size fluctuations or a biased sex ratio. The -population size, which dictates the effects of genetic drift on allele frequency change, can be considerably smaller than the - population size, which is the total number of individuals in the population. As a consequence of drift, heterozygosity -from one generation to the next.
Effective Census Decreases
Drag each statement to the correct box to indicate whether or not it is an expected outcome of long-term genetic drift in the five finite island populations shown in the figure.
Expected Outcome: The populations will diverge genetically over time. Either the A1 allele or the A2 allele will eventually be fixed in each population, but we can't say with certainty which one will be fixed in each.
A small number of individuals leaves a large population to colonize a new territory, such as an island. Under genetic drift, the allele frequency changes in this new colony are rapid. What term does this phenomenon describe?
Founder effect
The figure depicts a form of founder effect known as leading edge expansion, in which a small number of individuals at the periphery of a population colonize newly available habitats just outside the previous limits of the species range. Black spruce underwent such a process as glaciers retreated in North America. Plants initially colonize new habitats through seed dispersal, which occurs over relatively short distances and delivers both nuclear and mitochondrial DNA. Newly established populations also receive genetic material via pollen dispersal, which occurs over much longer distances and in much greater volume but brings only nuclear DNA into the new population. New northern subpopulations of black spruce have lower genetic diversity at mitochondrial loci than at nuclear loci, which is consistent with a founder event in which the population grew from fewer "mitochondrial DNA migrants" than "nuclear DNA migrants."
Leading edge expansion Seed Pollen Lower
Not all finite populations subject to drift are entirely homozygous for which of the following reasons?
Mutation introduces new alleles even as genetic drift erodes genetic diversity.
Expected coalescence time for a new mutation depends on whether the mutation is neutral or under selection. We expect a new mutation under positive selection to go to fixation rapidly and thus to have a more recent coalescent time than a neutral mutation. Since balancing selection maintains allelic variation, we expect a new mutation under balancing selection to have a less recent coalescent time than a neutral mutation.
Rapidly More recent Less recent
Drag each statement to the correct box to indicate whether it is true or false of the relationship between genealogy and mutation at a neutral locus.
True: The origin of new neutral mutations occurs randomly on branches of a coalescent tree representing the genealogy of the locus. The origin of new neutral mutations does not effect the branching pattern of a coalescent tree representing the genealogy of the locus.
When a Wright-Fisher population is subject to both mutation and drift at a neutral locus, at what population size and mutation rate will heterozygosity be lower?
When population size is small and mutation rate is low
Drag each statement to the correct box to indicate whether it is correct or incorrect of allele frequency change under genetic drift.
Correct Answers: Random fluctuations in allele frequency from one generation to the next are more pronounced in small than in large populations under genetic drift. In a Wright-Fisher population, genetic drift reduces heterozygosity by an average factor of ½N each generation. At any given time, the probability that a neutral allele will eventually be fixed in a population equals the frequency of the allele at that time.
If we were to run drift simulations for multiple populations of 500 individuals each, how would the results differ from those shown for populations of 10 individuals? Drag each statement to the correct box to indicate whether or not it is an expected outcome of these simulations.
Correct answer: Each population would take longer to become fixed for one of the alleles.
Drag each statement to the correct box to indicate whether or not it is a conclusion you can draw from the graph on the right. Each point on the graph represents an island population of lizards. The island populations were connected by migration until about 12,000 years ago.
Correct conclusion: Lizard populations are likely larger on larger islands and should thus have greater heterozygosity than populations on smaller islands. Genetic drift has likely driven genetic divergence among these lizard populations.
The neutral theory predicts that the neutral substitution rate equals the neutral mutation rate and is independent of population size. This theory predicts a molecular clock that ticks at a constant rate per generation. However, many studies have revealed rates of molecular divergence that are proportional to absolute time even among species with dramatically different generation times. Tomoko Ohta developed a theoretical solution to this puzzle with her nearly neutral theory, which posits that most substitutions are not truly neutral but actually slightly deleterious and thus subject to both genetic drift and purifying selection. Weak selection dominates over drift only in populations above a certain size; in smaller populations, even deleterious mutations evolve as if they are neutral. The nearly neutral theory thus predicts that substitution rate per generation is higher in smaller populations. The clock ticks at a constant rate with respect to absolute time because species with small populations also tend to have long generation times, and the effects of population size cancel out.
Generation Nearly neutral Purifying Higher
When results of the McDonald-Kreitman test are consistent with positive selection at a locus, what is true of the ratio of nonsynonymous to synonymous differences between species?
It is higher than the ratio for polymorphic variation within species, suggesting that divergence was associated with adaptive evolution of the encoded protein.
When a population is subject to both drift and selection at a locus, we expect selection to dominate in its effects on allele frequency change when population size is -and selection is -. We expect drift to dominate when population size is -and selection is -
Large Strong Small Weak
In the 1960s, comparisons of amino acid sequences revealed linear relationships between amount of sequence difference and time since species diverged from a common ancestor. These observations led to the concept of a molecular clock, which posits that sequences evolve at a constant rate over time and at the same rate in different lineages. This constant rate suggests that all members of a clade should show the same degree of sequence divergence from a common outgroup, a prediction known as the genetic equidistance principle. However, when substitutions occur at sites that already differ between species, the number of differences between lineages is a poor indicator of their time since divergence from a common ancestor. This phenomenon, known as saturation, complicates the utilization of sequence data for phylogenetic inference.
Molecular clock Genetic equidistance Saturation
We can use the neutral theory as a null model to reveal the operation of non-neutral evolutionary processes. For example, statistical tests assume that a neutrally evolving gene will have a ratio of nonsynonymous to synonymous substitutions that reflects the fraction of mutations that could possibly give rise to each. A ratio with an excess of nonsynonymous substitutions relative to neutral expectations suggests that the gene has evolved under positive selection, whereas a ratio with a deficiency of nonsynonymous substitutions is consistent with a history of purifying selection.
Null model Positive selection Purifying selection
In the image below, click on the arrow representing the sampling event that drives random change in allele frequencies in finite populations under the assumptions of this model.
Second arrow
Match each definition on the left with the correct term on the right.
Synonymous change: a point substitution/mutation in a DNA exon that does not result in a different amino acid at the corresponding position in a protein Mutation: a change in the DNA sequence of an individual Pseudogene: a nonfunctional segment of DNA derived from a previously functional gene Substitution: an evolutionary fixation of a new allele in a population
Watch the animation and examine the figure to the right, which depicts the substitution rate at nonsynonymous sites relative to the substitution rate at synonymous sites for 835 mouse-rat gene pairs. Which of the following conclusions can you draw from the graph?
Synonymous substitutions are more common than expected if their proportion reflected the ratio of synonymous to nonsynonymous changes in the genetic code overall.
The graph to the right depicts a decline in heterozygosity in overfished populations of New Zealand snapper. Hauser and his colleagues concluded that genetic drift had generated these declines even though the fishery census count suggests there are at least 3 million individuals (2002). If the population is so large, how might genetic drift lead to a loss of heterozygosity?
The census size is different from the effective population size. If the effective population size is much lower, only a small proportion of individuals breed each generation.
Which of the following statements is true about coalescent time in a Wright-Fisher population?
The coalescent point for all current gene copies in a population is more recent in a small population than in a large population.
Which of the following conclusions can you draw from the graph below? The calculations that generated this plot assume that the advantageous allele starts at a frequency of 1% in the population. s is the selection coefficient against the deleterious allele.
The effectiveness with which natural selection can fix an advantageous allele depends on population size and the strength of selection.
Imagine 10 replicate populations of 1000 individuals that go through a bottleneck that reduces each population to 10 individuals. At the bottleneck, allele frequencies fluctuate more wildly within each replicate population and diverge among the populations during the bottleneck. Each replicate population returns to a size of 1000 individuals after the bottleneck. Which statement below best describes the trajectories of allele frequency change once the populations have all returned to N = 1000?
The fluctuations decrease once the populations return to N = 1000, and the allele frequency in each replicate fluctuates around the value found at the end of the bottleneck
Imagine two randomly mating populations with equal allele frequencies, p and q, at a locus in the current generation. One population has 10,000 individuals, and the other has 50 individuals. There is no selection, migration, or mutation in either of these populations. Which of the following statements is true of the observed genotype frequencies in these two populations in the next generation?
The genotypes will likely occur at frequencies very close to p2, 2pq, q2 in the large population but deviate from those frequencies in the small population.
Imagine a group of islands, each of which is home to a population of 10 diploid individuals. Match each description on the left with the correct graph on the right.
The island populations have been genetically isolated from each other for many generations: 0.30 at 0 and 20 Migration among the island populations, which once occurred at a high rate, has recently been eliminated: Bell curve All island populations have been interconnected by high levels of migration for many generations: 1.0 at 10
What does the neutral theory of molecular evolution contend?
The majority of changes in DNA sequence arise due to genetic drift and have no impact on the phenotype.
Drag each statement to the correct box to indicate whether it is true or false of the results depicted in the graphs below.
True: Based on these data, it is possible that northern and southern elephant seals differ in their genetic variation because of some factor other than the hunting-induced bottleneck. The graph on the right shows that northern elephants seals show some DNA sequence variation even though enzyme electrophoresis revealed no heterozygosity at the loci examined. Reduced heterozygosity in northern elephant seals is consistent with a population bottleneck.
Which of the following conclusions can we draw from the figure, which depicts mtDNA types found in northern elephant seals sampled before, during, and after their hunting-induced bottleneck?
There was much more variation in the population before the bottleneck than during or after the bottleneck, indicating that the temporary reduction in population size was responsible for the low levels of genetic diversity in current populations.
Which of the following statements best explains the different patterns depicted in this graph of sequence divergence in rapidly evolving poliovirus?
Transitions occur at a higher rate than transversions, so substitutions saturate more rapidly than for transversions.
The figure shows the results of a test for positive selection associated with adaptive radiation in the Hawaiian silversword alliance (Barrier et al. 2001). The graphs depict Ka/Ks ratios for comparisons between pairs of species in two regulatory genes associated with flower development. The top graphs are from tarweeds, which have not undergone a recent radiation, and the bottom graphs are from silverswords. The vertical dotted line represents the mean value of Ka/Ks for each regulatory gene.Drag each statement below to the correct box to indicate whether it is true or false of these results and the conclusions they support.
True: Many, but not all, comparisons in silverswords were consistent with positive selection. All comparisons in tarweeds were consistent with purifying selection.
Drag each statement to the correct box to indicate whether it is true or false of the processes depicted in the figure.
True: The difference in allele frequencies between the island and mainland populations is due to the founder effect followed by the effects of genetic drift. In an island population initiated by five seeds sampled from the mainland, the most likely frequency of the R allele is the same as its frequency on the mainland.
Drag each statement to the correct box to indicate whether it is true or false of the results shown in the figure, which depicts patterns of molecular divergence between strains of the HIV-1 virus.
True: The pattern of divergence in the V3 loop region of the HIV-1 genome suggests a history of positive selection. Divergence at synonymous and nonsynonymous sites is clocklike in both of these genes.
Drag each statement to the correct box to indicate whether it is true or false.
True: The probability that a new advantageous mutation will rise to fixation via selection depends on the strength of selection. In a natural, diploid population, we expect that genetic drift will be the main driver of allele frequency change when the selective advantage of an allele is much less than ½Ne.