Knowing your genes: myostatin

More and more in recent years, the term myostatin has been thrown about, whether at sales or in AI catalogues. While the majority have little knowledge of the gene, testing has become common due to its ease.

That said, the double-muscling syndrome myostatin is not a new phenomenon and was first documented 200 years ago.

Some people are quick to condemn carriers over non-carriers without properly assessing the benefits some of these genes can carry or the status of their cow or heifer.

With Ireland at the forefront with regard to the collection of beef genomic samples, it stands in the best position to make the best possible use of all the myostatin gene data.

In 2020, the first tranche of the BDGP scheme is set to finish and with it comes millions of genotypes. Any future programmes run by the Department of Agriculture and the ICBF could benefit greatly from testing these already-collected genotypes for myostatin genes.

This would allow programme participants to select sires based on their cow herd myostatin status. In turn, this would increase the muscling of calves by selecting for different genes without affecting calving traits.

In cattle, double muscling is largely due to the loss of function of the myostatin gene, which, in turn, is due to a mutation in the gene.

Most of the major breeds in Ireland have already been identified as carrying a mutation in the myostatin gene and show hereditary double-muscling.

Case variants have been successfully identified in Angus, Aubrac, Belgian Blue, Blonde, Charolais, Limousin, Salers, Shorthorn, Parthenaise, Piedmontese and Simmental populations.

To give a background of the genes, the benefits they carry and the possible disadvantages for double carriers, we look back over an article written by Dr Alan Kelly from UCD. He explains what the myostatin genes are along with the benefits and risk.

What are myostatin genes?

The myostatin gene (GDF8) is found in all mammals and influences the production of a protein that controls muscle development.

The gene has been an important find, as it represents one of the first genes identified with large effects on important traits such as meat yield and quality.

Several mutations of the gene produce proteins that are less effective at controlling muscle development, which results in increased muscle mass in cattle. There are nine known mutations of the myostatin gene in cattle, some of which are breed-specific and others which affect more than one breed.

Six of these variants are classified as disruptive – nt821, Q204X, nt419, E226X, C313Y, E291X – and three other variants – S105C, F94L, D182N – are referred to as missense.

The six disruptive myostatin genes cause muscle hypertrophy (double-muscling) in cattle, but are also associated with larger birth weights, increased dystocia and enhanced tenderness.

The three missense myostatin genes will increase muscularity, but not cause double-muscling, and reduce external and intramuscular fat, with no change in birth weight.

Myostatin genes are recessive and thus only come to their full expression and effect when an animal carries any two copies.

So, for the full expression of double-muscling to occur in cattle, there has to be a complete absence of functional myostatin protein, which requires that both copies of the myostatin gene be defective (disruptive).

An animal inherits two different genes – one from its mother and one from its father. Recessive means that if one myostatin gene and one normal gene are present in the same animal, the myostatin gene will be suppressed by the opposing dominant non-disruptive gene inherited from the other parent.

For example, when one myostatin and one normal gene are passed on to a calf, the calf may show some extra muscling, but will never show extreme muscling from having only one myostatin gene. The normal gene will overpower the myostatin gene and stop extreme muscle growth.

Outcomes with ‘none’, ‘carrier’ or ‘double muscle’ animals

With DNA testing, cattle can be classified based on their myostatin results as:

The following are the different outcomes when breeding with none, carrier and double muscle:

What happens if you breed an N animal to another N animal?

What do you get if you breed an N (0 copies) with a C (1 copy)?

What do you get if you breed a C to a C?

What do you get if you breed a C to a DM?

Benefits and risk with myostatin

If we examine the benefits, myostatin genes have been proven to improve all the economically relevant carcase traits.

Additive effects are seen for increased carcase and meat yield and a higher proportion of high-value meat cuts in the carcase, improved muscle-to-bone ratio and dressing percentage.

Meat from double-muscled cattle tends to be of better quality due to a combination of increased tenderness, reduced fat content and a higher proportion of polyunsaturated fats.

Additionally, cattle with the myostatin variants have greater feed and lifetime production efficiency, thereby conferring economic and environmental benefits.

In quantifying the improvements in retail beef yield and meat quality, research studies have shown significant advantages to be gained even in cattle with only one copy of the myostatin gene (heterozygous) present.

At the same age, these cattle have 1% to 3% higher dressing percentage, 3% to 10% more lean meat yield and 13% less fat relative to conventional contemporaries.

Meat is more tender in relation to both overall tenderness (sheer force) and tenderness, due to reduction in meat toughness from connective tissue and collagen content.

From a disadvantages viewpoint, care should always be taken when selecting for and breeding with double-muscled animals due to calving, fertility and fitness concerns.

These difficulties can be manifested within a herd if animals carrying nt821 and Q204X are mated to animals that are carrying or are homozygous for the double-muscled mutations.

Given that some of these combinations will result in half of all calves being double-muscled, this heightens the potential of calving problems due to increased birth weight and subsequent breeding problems in the herd females, such as lower milk and fertility.

Research

Collectively, the research work on this topic in France and Australia shows that the incidence of dystocia increases with calves that are homozygous for the double-muscled mutations, but heterozygous calves did not experience any calving problems.

Also, cows heterozygous for a myostatin mutation (one copy) had similar conception rates, calving percentages and milk production when compared with normal cows.

Thus, for some beef breeds, undoubtedly there are advantages to be gained from breeding heterozygote animals due to their increased retail beef yield and production efficiency.

Knowledge on the myostatin genotype is an additional bit of information that may help decision-making, especially with regard to specific matings within the herd and also to potentially avoid procreating animals with calving and fitness-related problems.

Three societies using myostatin are Angus, Limousin and Charolais. Here’s their feedback

Anthony Mulligan of the Irish Angus Cattle Society said:

“The Irish Angus Cattle Society implemented myostatin testing in 2019 and will continue to do so in 2020 for any animals participating in the society’s major show and sales events - these being the Aldi ABP Irish Angus all-Ireland bull calf championship at Iverk Show, the Irish Angus Cattle Society all-Ireland Finals in Strokestown and the Irish Angus elite sale.

“The testing criteria for the Aldi Irish Angus all-Ireland bull calf championship is that all bulls must be tested for myostatin before qualifying; for the Irish Angus all-Irelands in Strokestown, all animals – both male and female – born from 01/08/19 onwards must be tested for myostatin; and for the Irish Angus elite sale in Carrick-on-Shannon, all animals must be tested.

“In Angus cattle, the myostatin gene that is most commonly found is the nt821 and less frequently the F94L. Animals that are carrying two copies of both these genes are not eligible for entries to the above events.

“Any myostatin gene found within the Angus breed would have to be questioned, as it takes a lot of the relevant characteristics that make an Angus from the breed. Other major negatives include increased calving difficulty, poorer fertility and fitness concerns.”

Paul Sykes of the Irish Limousin Cattle Society said:

“This is an area that raises as many questions as answers. We are not aware of any trials done here in Ireland or the UK to quantify the effects of any of the disruptive myostatin variants. You would expect their effect to be one which increases muscle mass, but at what expense is generally unknown, whether it be dystocia, milk ability, fertility, pelvic cavity or calving ability. This is further complicated by each MH variant and their interaction between the genes.

“It would be interesting to see the ICBF do trials to examine the relationship between MH genes upon meat tenderness, dystocia, milk ability, fertility and maternal calving ability.

“Speculation about the effects of MH variants can be costly and dangerous or a missed opportunity for both pedigree and commercial breeders. To say that bulls carrying double muscle genes are hard calved could be unfair.

“For example, in France we know of a homozygous double-muscled bull and his calving figure is 100, while another which is heterozygous double-muscled is very easy calving with an index of 124.

“What we do know is the F94L myostatin gene increases carcase yield, growth and feed conversion without impacting calving. F94L, commonly referred to as the profit gene, is proven to have a high incidence within the Limousin population.

“To date, there is no compulsion on breeders to test for myostatin, but we can publish results in the sales catalogues if made available by the breeders. We are also requesting that bulls being coded for AI are also tested for myostatin.”

Nevan McKiernan of the Irish Charolais Cattle Society (ICCS) said:

“From 1 January of this year, all animals entered in official ICCS sales must be genotyped and myostatin tested.

“The society is covering the cost of the myostatin test on these animals for 2020. The two variants being tested for are F94L and Q204X.

“The myostatin status of each animal will be displayed in our sales catalogues. Knowing the myostatin status of animals at our sales will hopefully help our customers and breeders to select breeding animals with the most appropriate myostatin traits for their breeding programmes.

“This will inevitably improve calving ease, carcase conformation and quality, without compromising on key maternal traits such as milk and fertility.

“Research has shown that there are pros and cons of each of the two variants. The F94L, commonly known as the profit gene, has been found to increase the size of muscle fibres, with no associated increase in calving difficulty, or lowered fertility, longevity or milking ability in females.

“The Q204X is more commonly found in the Charolais breed. Animals carrying the Q gene have been found to exhibit greater muscle development, rounded thighs, with reduced fat cover and greater meat tenderness. However, they may also have heavier birth weights, as well as slightly reduced milking ability and calving ability in females.”

Commercial buyers need to make themselves aware of these genes before striking off a possible purchase this spring bull sale season.

Participants in the BDGP scheme have the option of myostatin testing all their genotyped females for as little as €6 each. By doing this, it means you can purchase a bull that could add significantly to your bottom line.

Perception

Much of the negatives surrounding myostatin come from the perception that it affects calving traits. Much of this only occurs in the scenario where a double carrier of a gene is born.

By identifying single carriers in your herd, you can avoid selecting single-version carrier bulls for that same gene.

This means added carcase weight and added conformation without added calving difficulties.

The majority of all AI bulls now have a myostatin status printed alongside each bull, meaning it’s easier than ever.

However, this is only a tool and should be looked at along with knowledge of the pedigree and phenotypic characteristics.

The variants

Q204X – Animals with two copies of the gene (ie Q204X/Q204X) will exhibit characteristics of larger loin depth, reduced fat cover and greater meat tenderness. However, they may also have the potential to exhibit larger birth weight and, if females, slightly reduced milking ability. Animals that are heterozygous (single carrier) will still exhibit quality carcase characteristics, but are less likely to be affected by larger birth weights and reduced milking ability.

NT821 – Animals with two copies of the gene (ie nt821/nt821) will exhibit characteristics of larger loin depths, reduced fat depths and large, rounded rump and thighs. Animals with two copies may also have slightly heavier birth weights, bringing with it the potential for more difficult calvings. If animals are heterozygous (single carrier), they will still exhibit quality carcase characteristics, but are less likely to be affected by more difficult calvings.

F94L – Animals with two copies of this gene (ie F94L/F94L) exhibit an increase in muscling (by up to 19%) with no associated increase in calving difficulty, lowered fertility or longevity. Heterozygous animals (single carriers) also exhibit these characteristics, but not to the same degree.

E226X – Animals with two copies of the gene (ie E226X/E226X) will exhibit characteristics of larger loin depths, reduced fat depths and large, rounded rump and thighs. Animals with two copies may also have slightly heavier birth weights, bringing with it the potential for more difficult calvings. If animals are heterozygous (single carrier), they will still exhibit quality carcase characteristics, but are less likely to be affected by more difficult calvings.

Further variants

Three further variants of Myostatin exist in the population but are relatively uncommon in their occurrence. Known as nt419, E291X and C113Y, their effects are similar to nt821 and Q204X respectively.