POPULATION GENETICS AND BREEDING
by John Armstrong
Early
genetics
When Mendel's work was
rediscovered at the beginning of the twentieth century, the new field of
Genetics went in several directions. The T. H. Morgan (1) school quickly got
tired of crossing green to yellow peas and moved on to discovering white-eyed
fruit flies, linkage and genetic maps. The Garrod (2)
school started trying to figure out how genes controlled metabolism... and
eventually everything else. The mathematically inclined, fearing to get their
hands dirty, started thinking about how genes get shuffled around in a
population. That led, around 1910, to the famous Hardy-Weinberg formula that
relates the frequency of alleles to that of genotypes. For those unfamiliar
with it, the basic formula assumes two alleles for a gene and sets the
frequency of the first allele as p and that of the second one as q where p + q
= 1. In a population that meets certain conditions, the relative frequencies of
the three genotypes AA, Aa
and aa will be p-squared, 2pq and q-squared. The main
conditions are random mating, a large population, and no forces acting to
change the allele frequencies.
This does not imply an endorsement of random mating, but was simply
a starting point for the eventual development of equations to describe other
situations. Most natural populations do not follow these rules. In nature,
selection is often harsh, and most animals do not practice random mating. In
many species that live in packs or herds, only the dominant male may breed and
competition for that spot may be intense. Otherwise, the most common practice
is probably assortative mating, where mates are
chosen that have similar qualities (size, temperament, etc.) or are not closely
related (negative assortative mating). How they
decide on the latter is still being determined, but recognition of relatives
probably depends on pheromones to a large extent.
Genetics
without color
In the beginning, all
geneticists held to much the same beliefs, or "model"– that there was
one, and only one, good (or "wild-type")
version of each gene. There were also a few nasty recessive mutants that would
occasionally surface. They didn't really expect to find a large amount of
diversity for most genes. They lived in a black-and-white world where genes
were like light switches – either on or off, no in-between. As
most of the bad mutations appeared to be recessive, good breeding was reduced
to finding ways of efficiently identifying those carrying "degeneracies". Faith in inbreeding as a method
for breeding the perfect individual was reinforced by various authors:
"Inbreeding... is a method
of holding fast to that which is good and of casting out that which is bad. It
establishes homozygous purity..." Onstott (1946)
The morgan and garrod
geneticists wanted nice "clean" mutations that were easily
distinguished from the wild-type, and a population geneticist would never stoop
to thinking about what a gene actually does! Their main concern was to figure
out equations that would describe more complex situations involving selection,
migration, and mutation, and explain what would happen to a new mutation give
certain assumptions. Morphological variants, such as green and yellow peas,
were not even really thought of in the same way. I mean, can you really think
of a green pea as a "mutant"? (Or is yellow the mutant? How can that
be if it is dominant?)
However, by the early ‘60s, if not before, those on the front lines
were certainly aware of mutations that retained partial function ("leaky
mutants"), even if they didn't want to work with them. By the ‘70s, the
population geneticists actually started going out into the field and measuring
the diversity in populations. They went in with the expectation of finding
little difference between most individuals in a population and discovered far
more than they had anticipated. The dust still hasn't settled completely. Logic
suggested that if there was a considerable amount of genetic diversity, then
there should be some reason for it. In a large population, the rare recessive
mutation has little chance of gaining a toe-hold, and if it gets to the level
where there are a noticeable number of homozygous mutants, selection will do
its best to push it down again.
Explaining
diversity
Several theories were proposed,
but somewhere along the line, the realization dawned that many populations are
actually a loose collection of small populations that are semi-isolated. In a
small population, random events take over and the frequencies of particular
alleles may change dramatically just by chance ("genetic drift").
Given enough time, these random fluctuations generally eliminate all but one
allele, which is said to be "fixed". How quickly this happens depends
on how small the population is. Unequal use of individuals in the population
increases the rate of allele loss because it decreases the effective population
size.
Alleles with dramatic effects on viability are still generally
selected against, but if the population includes several alleles of a
particular gene, the "best" choice will not always be the winner.
Sometimes an allele that reduces fitness by a small amount will take over. Over
time, a small population may accumulate enough of these sub-optimal mutations
for the impact to be noticeable.
Small populations also tend to become unintentionally inbred simply
because there are not enough ancestors for each member of the current
population to have a unique set (3). Neither intentional nor unintentional
inbreeding lead to changes in allele frequencies, unless combined with
selection, but they do lead to loss of heterozygosity.
The decrease in fitness that results from accumulation of suboptimal recessives
in the homozygous state is what we generally call "inbreeding
depression".
If there is an exchange of genes by individuals
crossing over into another population's territory, the reduction in fitness due
to gene loss will be reduced. The populations that we see in difficulty have
often been cut off from other populations preventing this essential migration
of genes. Canine examples include the Ethiopian and Mexican wolves, and the
grey wolves on
The
importance of breed origins
Some breeds of domestic dog have
evolved gradually over hundreds or perhaps even thousands of years. As most
were bred for a purpose, some selection must have been involved. If you want a
dog to guard your sheep, and it fails to do so, you are not likely to breed it.
However, if you have two good herding dogs, you might breed them to each other,
irrespective of their relationship. All the herding dogs in one valley may have
been fairly similar and closely related, but exchanges would have occurred
between neighboring valleys. If the population over a
more extended region was bred for a common purpose, they might constitute a
recognizable group, or breed, and it might acquire a descriptive name -- the
Bavarian Sheepdog for instance. Such naturally-evolved breeds would be unlikely
to have suffered major drift losses, even if they became locally inbred,
because sufficient diversity would exist in the whole population, and there was
no reason not to breed to a good sheepdog from another country. Whether one
regards stud books and closed registries as good ideas or not, providing that
sufficient numbers were admitted, such a breed should have at least started
with sufficient diversity.
In contrast, when a breed is deliberately created from a small
number of founders, the creator(s) generally concentrate first on inbreeding
and selection to define the qualities they are after, rather than increasing
the initial population and subsequently selecting for those that come closest
to meeting their goals. Such a beginning generally removes most of the genetic
diversity in the first few generations. If you have been unlucky or chosen
badly, there may be little you can do.
The same fate may befall a naturally-evolved breed ( "landrace") if there is no recognized registry
in the country of origin and too few founders are admitted into the registry
somewhere else. At least in these cases, the potential exists of petitioning
for reopening the stud book and admitting additional "founders". In
those cases where there is no such reserve, the solution might be a merger with
a closely related breed, or at least provision for some
interbreed crosses. There are a few documented cases where this has been
attempted in the last 20-30 years, but they have met considerable resistance.
Don't
shoot the messenger
Population genetics is not
really a new discipline, it just seems that way because it's generally the last
chapter in a genetics text. Population geneticists are neither white knights come to save us all, nor agents of the devil intent
on destroying pure breeds. Population genetics is a tool for looking at an
entire population or breed. It can tell you what has happened to the genetic
diversity, and whether there is any possibility of improving the situation by
making appropriate crosses. How this information is used is up to the breed
club and individual breeders. Though lessons may be learned from conservation
biology, I do not expect breed clubs are going to be in a position to manage
the entire breed. However, they may choose to limit certain practices for the
overall good of the breed. The prime target, in my opinion, should be overuse
of popular stud dogs.
In a managed population of an endangered species, zoo biologists
might choose one of several strategies that are generally aimed at conserving
the diversity from the wild population from which the captive population is
drawn. This makes the assumption that all founders were equally meritorious and
that their genes are all equally worthy of preservation. This is essentially a
holding action and, in the absence of selection, runs the risk of creating a
population that is less well adapted to returning to the wild.
In my view, the best strategy for dog breeders is carefully planned
assortative mating combined with an attempt to
minimize or at least reduce the inbreeding coefficient. In practice, if I am
asked for an opinion on a suitable mate for a Standard Poodle, I suggest that
the breeder assemble a list of dogs he/she would consider breeding to, based on
conformation, temperament and whatever other criteria are deemed relevant, and
I will tell them the inbreeding coefficient for each potential litter and also
about the prominent ancestors in the pedigree. My personal criterion is a
10-generation COI under 10%, but I might pick one close to that, or even a bit
over, if I liked the other qualities.
The COI has predictive value. I can tell you that an SP inbred to
only 5% will, on average, live about 3 years longer than one bred to 35%, and I
can tell you that a 10% increase will likely reduce litter size by about 7%.
Both these effects are, in my opinion, most likely to result from accumulation
of suboptimal alleles with small individual effects. However, inbreeding also
increases the probability of doubling up on any obviously deleterious traits
carried by a shared ancestor. I understand why breeders inbreed (or linebreed), but I don't agree that it is necessary to
produce good dogs (see Inbreeding and Diversity). As to the claim that
it can be used to uncover problems in the line, I agree, but I can also give
you case histories where the breeder has proceeded to ignore a hereditary
problem uncovered this way, and as a result spread it through the breed.
Neither population genetics nor modern DNA technology is going to
provide magical solutions to all our problems. However, used together, they may
take us through the 21st Century. Continued reliance on the models put forward
in the early days of genetics almost certainly will not.
Notes:
- Thomas Hunt Morgan (Nobel Prize, 1933) and
his group provided the first evidence that genes were located on
chromosomes, and showed how they could be mapped.
- The first clearly-described relationship between genotype and
metabolic deficiencies is credited to Sir Archibald Garrod,
an English physician. (see The Nature of Genetic Disease)
- The theoretical number of ancestors increases exponentially: 2
parents, 4 grandparents, 8 greatgrandparents,
and so on. By time you have reached the 10th generation, you need 1024 in
that generation, or 2046 counting all the previous generations. The
highest number I have encountered in a purebred predigree
is just under 1000 for all 10 generations. 300-400 is more common and many
fall below that in a rare breed.
Copyright 2000 John B. Armstrong. Reprinted
with permission. It may be
reprinted providing it is not altered and appropriate credit is given.
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