Does it really matter whether a species has low or high levels of

genetic variation? Biologists, conservationists, environmentalists,

and informed citizens all worry about the impact of environmental
change on the ecosphere. Although organisms cannot plan for
environmental change, the more variation that exists in
a population, the better prepared that population will be to adapt
to change when it does occur. Note that the level of genetic
variation within a population is dynamic: It reflects an everchanging balance between processes, both random and
nonrandom, which remove variation. Sometimes, the latter can
overwhelm the former, leading to low levels of variation that
cannot be reconstituted over ecological time scales. Researchers
understand that variation arises
through mutation and recombination, and they also know that
natural selection can remove variation from a population.
Moreover, scientists are well aware of the fact that real-life
populations are not infinite, as the Hardy-Weinberg model requires
us to assume. Together, these factors lead to a relentless loss of
variation, a process referred to as genetic drift.
Genetic drift is the reason why we worry about African cheetahs
and other species that exist in small populations. Drift is more
pronounced in such populations, because smaller populations
have less variation and, therefore, a lower ability to respond
favorably that is, adapt to changing conditions. Thus, it's not
just the number of cheetahs that worries usit's also the
decreased variation in those cheetahs.
Understanding the Mathematics of Drift
To get a feel for genetic drift, consider a population at HardyWeinberg equilibrium for a gene with two alleles, A and a. Let p =
the relative frequency of the A allele, let q = the relative frequency
of the a allele, and let p = q = 0.5. For no drift to occur, the
frequencies of the alleles in successive generations must remain
at 0.5. If N is the population size of diploid organisms, then the
number of A alleles (denoted k) is equal to 2pN. Given this

information, how can we calculate the

exact probability that k remains equal to 2pN after a generation of
random sampling? To do so, we begin with the general formula for
the binomial distribution:
Pr(k | p, n) = [n! / k! (n - k)!]pk(1-p)n-k
The binomial distribution is used when (a) there are two possible
outcomes of a trial, (b) the probability of each outcome remains
the same across all trials, and (c) all trials are independent of
each other. Here, the two possible outcomes (i.e., the allele
sampled in a gamete) are A and a, the probability of sampling a
gamete with the A allele is p, there are n = 2N trials
(i.e., gametes sampled), and k of these trials result in the A allele.
The term [n! / (k! (n -k)!)] gives the number of ways that one can
observe exactly k "successes" (defined here as A alleles) and n k "failures" (defined here as a alleles). The term pk (1-p)n - k is the
exact probability of observing any given order of k "successes"
and n - k "failures." Therefore, the product of these terms gives
the exact probability of observing k "successes"
and n - k "failures," given that one is unconcerned about their
order.
Using the formula for the binomial distribution, we can calculate
the exact probability that k = 2pN for a range of N. Doing so yields
the following results:
Population size (N)
Gene Copies (2N)
Pr(k | p, n = 2N)
At first glance, these results might seem backward. According to
the table, the probability that the allele frequencies will remain
unchanged is higher for the smaller populations! However, that's
only part of the story. In all of these cases, it's more likely that the
allele frequencies will change, and it is actually the magnitude of
the change that matters. To see what this means, let's focus on
those populations where N = 5, N = 50, and N = 500. Figures 1

through 3 show the probabilities of allele frequencies in the next

generation of each of these populations.

Figure 1: Probabilities of allele frequencies in the next

generation, in a population of five organisms (N=5).
2008 Nature Education All rights reserved.
Figure Detail

Figure 2: Probabilities of allele frequencies in the next

generation, in a population of 50 organisms (N=50).
2008 Nature Education All rights reserved.

Figure 3: Probabilities of allele frequencies in the next

generation, in a population of 500 organisms (N=500).
2008 Nature Education All rights reserved.
When looking at these figures, it should be evident that the
breadth of the distribution narrows as population size increases.
This is due to a decrease insampling error. So, while allele
frequencies are almost certain to change in each generation, the
amount of change due to sampling error decreases as the
population size increases. Perhaps the most important point is
that the direction of the change is unpredictable; allele frequencies
will randomly increase and decrease over time. Furthermore,
when change does occur, sampling to produce the next
generation will center on the new value of p. Thus, given enough
time, in the absence of factors that maintain both alleles
(e.g., balancing selection), p will drift to either 0.0 or 1.0; in other
words, one allele will drift to fixation, and the other will drift to
extinction. The time that it takes for this to occur depends on the
starting frequencies of the alleles and, of course, the population
size (see below under "The Population Genetic Consequences of
Ne").
Effective Population Size

Figure 4: The relationship between Ne and Nf in a population

of 1000 mating individuals.
2008 Nature Education All rights reserved.
Because most populations are large, it seems fair to ask whether
genetic drift is really all that important. It's true that most
populations are large, but they don't necessary act large. Thus,
the rate of genetic drift is not really proportional to census
population size (Nc). Rather, it's proportional to something more
abstract specifically, the effective population size (Ne). In an
ideal population of sexually reproducing individuals , Ne will
equal Nc. An "ideal" population has the following characteristics,
and most deviations will decrease the effective population size:
1.
There are equal numbers of males and females, all of whom
are able to reproduce.
2.
All individuals are equally likely to produce offspring, and the
number of offspring that each produces varies no more than
expected by chance.
3.
Mating is random.
4.
The number of breeding individuals is constant from one
generation to the next.
Essentially, anything that increases the variance among
individuals in reproductive success (above sampling variance) will
reduce Ne (the size of an ideal population that experiences genetic

drift at the rate of the population in question). For example,

consider the effect of unequal numbers of mating males and
females. In an ideal population, all males and all females would
have an equal chance of mating. However, in situations in which
one sexoutnumbers the other, an individual's chance to mate is
now affected by its sex, even if all individuals within each sex have
an equal chance to mate. In this situation, effective population size
can be predicted by the formula Ne = 4NmNf/(Nm + Nf), where Nm is
the number of males and Nf is the number of females. Figure 4
shows the relationship between Ne and Nf in a population of 1,000
mating individuals. In an ideal population, all individuals have an
equal opportunity to pass on their genes. In real life, however, this
is rarely the case, and Ne is particularly sensitive to unequal
numbers of males and females in the population.
The Population Genetic Consequences of Ne
One way to think about the relationship between Ne and genetic
drift is to consider the time required for the fixation of one allele or
the other if we assume selective neutrality. Motoo Kimura and
Tomoka Ohta (1969) showed that this timedenoted E(T)
depends on two parameters, Ne and p. Specifically,
E(T) = -4Ne [p ln p + (1-p) ln (1-p)] generations
Therefore, fixation time scales with Ne. This time is maximized
when p equals 0.5, and it falls off dramatically as one allele or the
other becomes more rare at the generation we consider to be our
starting point. Perhaps this is intuitive, but because intuition can
sometimes be misleading, it's good that a formal mathematical
treatment confirms our suspicions!
If we set p to 0.5, then one or the other allele should drift to
fixation, on average, in 2.77 Ne generations. This would be 13,863
generations for a population with Ne equal to 5,000. However,
if p is 0.25 (or 0.75), E(T) drops to 11,246 generations, and if p is
0.1 (or 0.9), E(T) drops considerably to only 6,502 generations.
Moreover, if p is 0.01 (or 0.99), we can expect fixation to occur in
just 1,120 generations.

Another way to think about drift is to consider the rate at which

variation is lost. As in the previous example, this depends
on Ne and the starting value ofp. Here, we define "heterozygosity"
(H) as the proportion of individuals who
are heterozygous (2pq under Hardy-Weinberg assumptions).
If H0 is the initial heterozygosity of the population, then the
heterozygosity after t generations (Ht) can be calculated using the
following equation:
Ht = (1-1/2Ne)tH0
According to this equation, H is expected to decline by a factor of
1/2Ne in each generation. Thus, the lower the effective population
size, the faster heterozygosity will be lost.
Changing Population Size
Effective population size is also sensitive to changes in census
population size over time. In a discrete generation model, Ne is
calculated as the harmonic mean of the population sizes at each
generation (i.e., the reciprocal of the mean of the reciprocals), as
shown in the following equation:
Ne = [SNi-1/k]-1
In this equation, Ni is population size at generation i, and k is the
number of generations. Note that the harmonic mean is always
lower than the arithmetic mean (often considerably lower), and it
is especially sensitive to the lowest values of Ni. This has special
relevance to two related scenarios: a population bottleneck and
a founder event. In the case of a population bottleneck, population
size is substantially reduced for some period of time. In the case
of a founder event, a small sample of a larger population becomes
geographically isolated. In either case, the population size is
dramatically reduced, at least temporarily. The effects of this
reduction on genetic variation depend on both the size of the
population during the reduction phase and the duration of the
reduction phase.
Let's place this idea in context. Consider that, depending on the
measure used, randomly chosen humans tend to differ at less

than 1/1,000 of their DNApositions. Based on molecular

population theory, the implication is that humans have an effective
population size in the order of tens of thousands of individuals.
However, we know that our census population size is currently
well over 6 billion! Even though the human population has
exploded, our standing genetic variation largely reflects a much
smaller past population size. Remember, harmonic means are
especially sensitive to the smallest values, so our Ne still mainly
reflects the much lower past population size. In fact, it is almost
certain to do so for as long as humans survive as a species.
Barring the possibility of moving to another planet, the expected
eventual destruction of Earth by the Sun does not allow enough
time for us to recover a value of Ne close to our current census
size.
This concept is relevant to conservation as well. A species that
loses genetic variation to drift (e.g., because its census population
has gone through a severe bottleneck) will have a very hard time
recovering the lost variation, because Ne is most sensitive to the
smallest population sizes over time. In fact, even if the census
size of the population can be increased (perhaps through captive
breeding efforts), the genetic variation may continue to decrease,
because Ne still reflects the recent bottleneck.