January 29th, 2010
Bioe 109
Winter 2010
Lecture 10
Microevolution 3 - random genetic drift
- one of the most important shifts in evolutionary thinking over the past 30 years has been an appreciation of the importance of random genetic drift.
- prior to this time, the prevailing view was that most, if not all, characters of organisms were shaped by natural selection.
- stochastic, or random, processes were deemed to be of minor importance.
- the pendulum has now swung back to a considerable extent and drift is now realized to play an important role in evolution - especially at the molecular level.
What is random drift?
- random genetic drift may be defined as random changes in the frequencies of neutral alleles from generation to generation caused by “accidents of sampling”.
- “accidents of sampling” refer to random events that result in mistakes in the transmission of genes across generations.
- these accidents of sampling arise because populations are finite in size.
and that by chance, not all individuals, will successfully propagate their genes into the next generation.
How can alleles be neutral?
1. mutations in non-coding DNA regions
- point mutations in most non-coding DNA sites likely are likely neutral in their phenotypic effects.
2. mutations involving silent, or synonymous, changes
- for example, a CUC to CUU mutation (both codons specifying leucine).
- this mutation does not result in an amino acid substitution thus should be invisible to the selective process.
- however, the phenomenon of codon bias (the nonrandom usage of codons specifying the same amino acid) at some genes in bacteria, yeast, and Drosophila suggests that even silent mutations may not be entirely neutral.
3. mutation among very similar amino acids
- for example, consider a mutation from leucine (CUC) to valine GUC)
- both represent small, non-polar amino acids that differ slightly in size.
- if this change occurs in a “non-critical” area of the protein, it may have a negligible effect on function.
- in other words, the fitness of an individual possessing this new mutation may be indistinguishable from its predecessor.
How does random genetic drift occur?
- a good analogy for the process of drift is the blind sampling of different colored balls (gametes) from an urn.
- random drift operates in this example because the color of the ball (gamete) cannot be detected by the “blind” sampling process.
- the different colored balls would represent the frequencies of different neutral alleles at a locus.
- suppose we have an equal mixture of blue and white balls (gametes); p (blue) = q (white)= 0.50.
- suppose that we were to sample 20 million balls from the urn to form the next generation.
- because of this large sample, we would expect the frequencies to not deviate very much from 0.50.
- for example, we could obtain a sample of 10,000,106 blue balls and 9,999,894 white balls.
- the frequency of p has thus increased to 0.5000053 and q decreased to 0.4999947.
- suppose, however, suppose that we sample only 200 balls every generation (again from a starting point of p = q = 0.50).
- by chance, we could obtain a sample of 94 blue and 106 white.
- in this sample, the frequency of blue has dropped to 0.470 and white increased to 0.530.
- this result indicates what our intuition would tell us - the magnitude of random drift is more prevalent in small populations.
- the smaller the population, the greater the chance that sampling error will result in allele frequency change.
- random fluctuations in the transmission of genes will tend to “even out” in very large populations by the law of large numbers.
- therefore, the magnitude of random genetic drift is simply inversely proportional to the effective population size.
- each generation, a population will lose variation in proportion to the term 1/2Ne, where Ne is the effective population size.
Some properties of random genetic drift
1. Magnitude inversely proportional to effective population size (Ne)
2. Ultimately results in the loss of variation from the population.
3. The probability of fixation of a neutral allele equals its frequency in the population.
4. Random drift will cause isolated populations to diverge genetically.
5. Is accentuated during population bottlenecks and founder effects (see below).
What is effective population size?
- a species’ effective population size is not the same as the census population size that we observe in nature.
- in general terms, the effective population is roughly equivalent to the actual number of breeding individuals in the population.
- this will always be lower than the current number of individuals present in the population.
- this can be thought of as the contemporary effective size.
- Ne is also strongly influenced by the longer-term history of a population.
- this is more reflective of its evolutionary effective size that are largely responsible for its standing levels of genetic variation.
- three factors exert strong effects on effective population size.
1. Fluctuations in population size.
- if populations fluctuate in size over time, the effective size is equal to the harmonic mean of the actual population numbers:
1/Ne = 1/t(1/N1 + 1/N2 + 1/N3 + .... + 1/Nt)
- here, N1, N2, etc. are the population sizes in generations 1, 2, etc.
- the harmonic mean is strongly influenced by the smallest population sizes.
- for example, if in three generations a population had sizes of 2000, 30, and then 2000 (i.e., it went through a population bottleneck) then the effective size is only 87.4, whereas the numeric mean is 1343.
- long-term fluctuations in population size are believed to play a dominant role in producing much smaller effective population sizes than are suggested by current population sizes.
- in the temperate north latitudes, for example, glaciation events are believed to have led to dramatic reductions and then expansions in the population sizes of most all species. The “effective population size” may thus be much smaller than suggested by the current size.
- the same may hold true for many tropical species whose ranges may have contracted greatly during periods of glaciation.
2. Unequal numbers of males and females.
- here, the sex which contributes a lower number of gametes will experience a “bottleneck” and thus be subject to genetic drift. The effective population number is thus:
Ne = 4NmNf
Nm + Nf
- here, Nm and Nf refer to the number of males and females, respectively.
3. Variance in reproductive success.
- if there is a large variance in the number of progeny produced by individuals the effective population size further reduced below the census size.
- all of these factors contribute to making effective population sizes considerably lower than what we may think from current population sizes.
Genetic Bottlenecks and Founder Effects
- genetic bottlenecks, or severe reductions in population sizes, may dramatically reduce genetic variation through pronounced genetic drift.
- two of the most extreme examples known involve the northern elephant seal (Mirounga angustirostis) and the cheetah (Acinonyx jubatus).
- the northern elephant seal was almost hunted to extinction in the late 19th century - it is estimated that only 20 - 30 individuals survived
- the species has now rebounded to a population size of approximately 150,000 - 180,000.
- the Northern elephant seal was surveyed for genetic variation at 24 electrophoretic, or allozyme, loci by Bonnel and Selander (1974).
- surprisingly, it was found to possess no genetic variation at this sample of loci!
- the Northern elephant seal is an interesting case in that the population has rebounded and appears to being do fairly well without polymorphism that is commonly found in other large mammals.
- populations of the East-African and South African subspecies of the cheetah have been surveyed for 52 loci.
- a sample of 30 individuals from the EAP gave P = 0.04 and H = 0.01.
- from a sample of 98 individuals from the South African group, P = 0.02, and H = 0.004.
- these are extremely low estimates. Even more surprising was the finding that skin grafts among unrelated individuals from the South African subspecies are not rejected. This suggests that the cheetah is monomorphic at its major incompatibility or MHC locus which is abundantly polymorphic in all other mammals.
- further evidence that the cheetah is possesses diminished levels of variation comes from observations that male cheetahs have a high incidence of abnormal spermatozoa and attempts to mate cheetahs in captivity have met with little success.
- furthermore, a recent outbreak of feline infectious peritonitis in the 1980's severely decimated many colonies of animals. It is interesting that the same virus caused only a 1% mortality rate in domestic cats. These observations support the suggestion that cheetahs have lost much of their reservoir of genetic variability and thus may be precariously poised on the brink of extinction.
- unlike the elephant seal there is no direct evidence for a bottleneck in the species' recent history.
- however, it is known that the cheetah used to have a much larger geographic range.
- although it is now endemic to the African subcontinent, it used to be found throughout Europe and Asia. Apparently, the species has undergone at least two severe bottlenecks resulting in the loss of much of their genetic variation.
Bottleneck size vs. duration
- the loss of genetic variation by population bottlenecks is a direct cause of genetic drift.
- simulation models have shown that the duration of the bottleneck (i.e., the number of generations spent at a reduced population size) is a more important factor determining the loss of genetic variation by genetic drift than is the actual population size itself.
- if population rebounds quickly from a bottleneck, little heterozygosity is actually lost.
- however, if the population remains at low levels for a large number of generations then random drift can greatly accelerate the loss of alleles.
- genetic bottlenecks also cause an elevation in inbreeding in the population.
- inbreeding does not actually cause alleles to be lost from the population - it simply shifts the distribution of genotypes to have more homozygotes than expected under random mating.
- this will typically result in the expression of deleterious recessive alleles in homozygous state leading to the phenomenon of inbreeding depression.
The interplay between drift, migration, and selection.
- we have now briefly examined the basic characteristics of natural selection, random genetic drift and gene flow.
- last week, last Monday we learned that Hardy-Weinberg equilibrium will be established in a population is there is no selection, drift, or migration.
- is this likely?
- NO: it is possible that selection, random drift, and gene flow all occur simultaneously.
- not all loci may be subject to selection, but random drift and gene flow will occur continuously.
- what is the interplay between these three microevolutionary processes??
- let us consider some of the possible interactions.
1. Gene flow and drift
- here we are considering neutral alleles.
- for neutral alleles, random drift and gene flow will act in opposition to each other.
- random drift leads to the genetic divergence of populations.
- random drift and gene flow will act in opposition to each other.
- the two parameters that will determine the outcome of this interaction are m, the strength of migration, and N (the effective population size) that will dictate the magnitude of random drift.
- if Nm > 1, gene flow overrides drift, populations are will remain genetically identical
- if Nm < 1, gene flow is too low, random drift can lead to genetic divergence.
2. Gene flow and selection
- gene flow and selection can act in opposition if selection favors different alleles in different populations.
- if the number of migrants entering a population each generation exceeds the effect that selection has imparted that generation, then no genetic change will occur!
- the crucial parameters are the strength of selection (s) and the magnitude of gene flow (quantified by the parameter m).
- if m > s, gene flow can overpower the affect of selection in local populations.
- if s > m, then selection can override the impact of gene flow and result in “local adaptation”.
3. Drift and selection
- random genetic drift and natural selection will act in opposition when population sizes become too small for the selective process to operate.
- selection results in the deterministic change in allele frequency!
- random drift results in stochastic changes in allele frequency!
- the relevant parameters are the strength of selection (determined by the selection coeffcient, s), and the effective population size (that will determine the extent of random drift).
- if Ns > 10, selection controls the fate of the allele.
- if Ns < 1, drift will overpower the effect of selection.
- when population sizes become too small the random fluctuations caused by drift exceed the deterministic selective trajectory.
- therefore, the same allele with the same selective advantage will be selected in a large population yet behave as if it is neutral in a small population (because random drift will override the effect of selection).
- in the first case, directional selection will always result in the fixation of the allele.
- in the latter case, the allele may drift to either fixation or loss.