Gene Modifiers in Persian Sheep

Dr Colin Walker BSc  BVSc  MACVS  OAM

Our understanding of genetics has changed tremendously over the last few decades. Most of us at school would have learnt about Mendel and how he discovered the science of genetics. With the development of molecular biology and the ability to sequence DNA our understanding of just how inheritance works is changing. What we now know is that genes make up only around 1% of our DNA. Yet 80% of our DNA is active. As it is DNA that actually makes an individual just what it is, it makes sense that it is the other 79% and not the genes that is the main game.

Two characteristics of genes are that they mutate rather infrequently and the changes they control are relatively strict, for example, a Persian  is either a skilder ( ie speckled ) or a kleur kop ( coloured head ) – there is no blended pattern in-between. Genes are controlled by smaller pieces of DNA called, logically, gene modifiers ( or sometimes DNA modifiers or hereditary modifiers ). By comparison with genes, these gene modifiers, mutate frequently and their pattern of inheritance is “blended”. For example if a big sheep is mated to a small sheep most of the young are medium sized.

Gene modifiers tell the genes what to do --  they make very subtle changes and mutate up to 100,000 times more often than genes. So they mutate much more often but the changes caused by these mutations are very subtle. This means that these modifiers more rapidly and more subtly can help animals to adapt but they can also be used by breeders to shift animals genetically.

Animal breeders have known this for millennia and have developed breeds of dogs, cattle, chickens and sheep etc long before Mendel discovered the science of genetics. They realized that if you kept selecting for animals that had the characteristics that were wanted then gradually the animals would change and develop into the desired animal. “Like breeds like” and “bit by bit” were the methods used.. All of these gradual changes occurred through mutations in the gene modifiers. In this way beef cattle gradually got bigger and commercial chickens laid more eggs.

The initial gene mutations that led to the unique features of Persian sheep, occurred centuries, possibly millennia ago. Some of these characteristics are totally unique to the Persian. Quite a statement considering there are over a thousand breeds of sheep in the world. You can’t fake a Persian.

Gene modifiers control many characteristics that can be hard to see or quantify such as foraging ability, heat tolerance and maturation rates. Sometimes it is easier to understand something that you can see more readily – like colour. Say , we were selecting for a colour , such as a pale red in a skilder. If we continued to select for this and only bred from the palest red sheep then eventually we would end up with an almost white animal. To produce this almost white animal a gene mutation would not have occurred but by continuing to select for the more rapidly mutating gene modifiers that make the sheep pale , eventually an almost white Persian could be  produced.

Gene modifiers often occur on the chromosome within the area where a particular gene exists. They are just short bits of DNA base pairs such as AAGT. If a gene has one bit of AAGT it might, using the colour example above, produce a little bit less colour. If it has say, three bits of this sequence, AAGTAAGTAAGT, then, reduction in pigment is more extreme. Aa animal  can have one hundred bits of DNA, and this can create major differences. The gene modifiers act as very precise and flexible volume controls on genes. Without knowing it we can use this effect to sculpt our sheep. Where the short  bits of DNA that modify genes and regulate their action are repeated they are called “tandem repeats”. Keep in mind that only around 1% of our DNA is genes and yet 80% of our DNA is active. The 79% that includes the gene modifiers is the main game.

Interestingly the first person to propose gene modifiers was Nobel Prize- winning scientist Dr Barbara McClintock. Information not only in the sheep world, but also the world generally can spread slowly. Dr McClintock realized as early as 1948 that DNA elements regulated genes by inhibiting or modulating their actions. Only much more recently have her theories been proven to be correct and applied . Genes are the factories and modifiers can be regarded as the staff and management which run each factory , bending genes to their will. Using a knowledge of these modifiers empowers us to create tomorrow’s sheep. Gene modifiers are readily heritable and so can relatively quickly alter the genetic makeup of a flock.

So genes control major characteristics and mutate infrequently. It is these gene mutations that have occurred through millennia that have made the Persian what it is today and set it apart from all other sheep breeds. It is the gene modifiers that mutate often, cause minor changes and have a blended pattern of inheritance that can be used to gradually mold the characteristics of a breed.

Looking at genetics from this perspective I find it much easier to understand much of what we are seeing in our Persians. For example how can it be that you have deep red Persians while others are a pale yellow colour and yet both are red speckles. How is that some kleur kops with deeply pigmented heads are called dilutes while others with pale heads are not dilutes? The answer is that some characteristics ( the major ones intrinsic to Persians such as the pattern and tail set )  are controlled  by genes . These characteristics are then modified through the action of gene modifiers. In this way a dilute red ie a roan can be any colour from an off white to a deep rusty red and a dilute black ie a blue can be anything from a dusty white to a steel grey. In a similar way a range of colours can be produced in non- dilute sheep.

A gene determines whether or not a Persian is a dilute colour or not. The gene for dilute alters the colour of the hairs turning black hairs blue and red hairs roan . It also intersperses white hairs throughout the coat. Dilute gene modifiers then affect the intensity of the colour and the number of white hairs interspersed throughout the coat. In this way It is possible for a kleur kop or skilder to have a very pale coloured head. Conversely it is possible for a dilute to have a deeply pigmented head. An interesting feature of the dilute gene is that sheep with this gene have a white scalp. This white area can extend over most of the forehead but according to the Standard should be as small as possible. (It must be noted however that the white scalp in a dilute is quite distinct from the white of a non-dilute skilder or Kleur kop extending up the neck onto the scalp. This is a serious fault that is highly heritable).

For those interested to illustrate these points there are pictures of skilders and kleur kops of variable colour intensity on the Coolibah Persian Sheep Stud site in the Gallery section.