John P. Gibson
Centre for Genetic Improvement of Livestock
Animal & Poultry Science, University of Guelph
Breeding of dairy cattle has had remarkable success. But how much do we really
understand about the detailed genetic makeup of our cattle?
Dairy cows are dairy cows and not dogs, cats, mice or any other animal
because of their unique genetic makeup referred to as their genotype.
The genotype consists of around 50,000 to 100,000 individual genes that
form a set of complex instructions which determine an animal's
characteristics. The genotype is analogous to an architect's plan, or a
manual of instructions, that when followed, leads to the construction of a
particular building. The genotype of a cow and a mouse, although sharing many
common principles, nevertheless are very different, much as the plans for an
office tower in Toronto will look very different to those for a dairy farm.
And, although the plans for any two farms will look very similar to each other
(at least in comparison to the plans for the office tower), subtle
differences in the plans describe the unique differences of one farm from
another. Similarly, each cow has its own unique genotype, its own set of
plans, which determine many of the individual characteristics of that cow,
such as her size, shape and colour, how much milk, fat and protein she will
give, and so on.
With genetic improvement we attempt to improve cattle by producing a better
genotype, a better set of plans. But, we still know very little about how the
genotype works. We don't even know exactly how many instructions there are
(50,000 to 100,000 genes is a rather vague statement), let alone what most of
those instructions say, how they are carried out or how they interact with
each other. Since we don't know what the instructions are, we practice
selection on the final product, the performance and looks of the cow and her
relatives (e.g. sire, dam, sisters). This is akin to deciding on which
architectural plans to use based on the looks and performance of the final
building. Just as we can choose a house or farm to suit our needs, so we can
choose cows, without necessarily understanding the complexities of the design
process.
It is here that the parallels with architectural design break down. An
architect can attempt to build a better house, one that is more attractive,
better to live in, more energy efficient, etc., by utilizing the best
instructions from different designs, and modifying other instructions based
on their understanding of the physics of building, the cost of materials and
the needs and resources of their client. Although errors certainly can and do
occur, the form and performance of the final building is fairly well
predicted in advance. With cattle breeding, each parent contributes a
randomly chosen one-half of their genes (instructions) to their progeny,
so that every progeny is unique. We have no control over this process,
and do not in any case know what most of the instructions are, so we have
to wait until all the progeny are born and start producing to judge the
success of this random selection of instructions. The process works, as
witnessed by the dramatic changes in performance of dairy cattle over the
past 40 years, but it is slow and inefficient. We could probably improve
our success by understanding more about the design at the level of the
instructions, the genes themselves.
Trying to understand the complexity of genetic instructions is a
daunting prospect. Consider the size of the problem. Think of the
genotype of a cow being an instruction manual. Each of the 100,000 genes
is about 4000 base-pairs in length, each base-pair being a letter in the
genetic alphabet. A standard book page with smallish print carries about
4000 letters. So to store this information, a genetic instruction manual
would have 100 volumes, each with 1000 pages. On top of this there is a
huge amount of genetic material that appears to have no function. For
every functional gene of 4000 base-pairs, there are about 40,000
base-pairs of non-functional, nonsense DNA; that is 10 pages of junk for
every page of useful information corresponding to a functional gene.
Thus the whole genotype is an instruction manual of 1100 volumes, each
with 1000 pages, in which for every page of useful instruction, there
are 10 pages of rubbish. Moreover, this manual comes with no contents
pages, indexes or reference keys, and is written in a highly complex
language we are only just beginning to decipher.
Impressive in its complexity, perhaps the real miracle is that all this
information is contained in the single copy of DNA passed on from the
sire, in the sperm cell, and from the dam, in the oocyte. This molecule
of DNA weighs a mere million millionth of a gram. To imagine how small
that is, it would take a thousand million million molecules to weigh the
same as a litre of milk. How many is a thousand million million? A
thousand million million quarters laid end to end would stretch to the
moon and back about 5000 times. A politician a thousand million million
miles from home would be about twenty times further away than Sirius,
the brightest star in the sky (some might argue that this is only a
little more distant than Ottawa). Suffice to say, a single DNA copy of
the genotype is extremely small and requires the most advanced
technologies to even begin to read it.
Every animal has two copies of the genetic instruction manual, and all
animals have the same basic instruction manual, except that there are
several different versions of each page in the population. This means
that, for a particular animal, page 42 in one copy of Volume 10 does not
necessarily read exactly the same as the other copy of page 42, Volume
10. And, page 42 from one animal is not necessarily identical to page 42
from another animal. Because there are several variants of virtually
every page, any two animals chosen at random will differ at several
thousand pages in the manual, and no two animals have exactly the same
set of instructions. (The only exceptions to this last rule are
identical twins and clones which carry identical copies of the whole genome.)
Most of the variations in pages (genes) between animals are relatively minor having no real effect. Some are sufficiently important to have a small effect and a few have large effects. We have long been able to follow the effects of those few variations in pages of instruction (genes) with large effect, such as the polled gene (causing lack of horns in some cattle breeds), the BLAD gene (bovine leucocyte adhesion deficiency, causing lack of vigour and early death in calves) and the double muscled gene (causing massive extra muscle growth in some beef breeds). But, most of the genetic diferences we see between animals are due to the many variations in individual genes that each have relatively small effect. A recent massive expansion in the science and technology of molecular genetics is now providing techniques to find and follow genes of smaller effect and is providing insights into the genetic architecture of animals. In subsequent articles we will look briefly at some of these technologies and how they might be of use in dairy cattle breeding.