population genetics of A1 & A2 milk

This is an item I originally wrote for the Science on the Farm website. But because I briefly mentioned the A1/A2 milk thing in the last post, I thought I could usefully bring this across to the Bioblog as well.

The 2006 Scholarship Biology paper included a question on the genetics of A1 and A2 milk. It’s worth revisiting this here, because it’s a good example of patterns of inheritance and the way an allele may spread through a population. (We are not going to discuss the possible public-health implications of the two alleles.)

Beta casein is one of 3 types of casein, the most common protein in milk. In turn, beta casein comes in 2 forms: A1 & A2. These two forms are identical, with the exception of the 67th amino acid in the polypeptide chain. The A1 form has a histidine in this position, while A2 has a proline.
There are two alleles involved in the inheritance of A1 & A2 beta casein. A cow with the homozygous genotype A1A1 produces pure A1 milk, while A2A2 produces pure A2. An individual which is heterozygous for this gene, A1A2, will give milk that contains a mix of the two forms of beta casein. In other words, this is an example of incomplete dominance. Scientists feel that the A2 allele represents the original form of the beta casein gene.

In a Friesan-based dairy herd, around 30% of cows will be homozygous for the A2 allele, with 30% homozygous for A1 and 40% heterozygous.  The proportion of A2 homozygotes is higher in Jersey herds – but there is also a lot of variation between herds (Woodward, 2004).

If the A2 allele was, as scientists believe, the original form of the beta casein gene, how did the A1 allele arise and what explains its present distribution in the NZ dairy herd?

Since the A1 & A2 forms of beta casein differ by only a single amino acid, the A1 allele must have originated as a point mutation in the beta casein gene.  And this mutation must have occurred in the germ-line cells that produce gametes. or during gamete production itself, otherwise the A1 allele could not have entered the gene pool.

How would natural selection act on indivduals carriying this new allele? Because casein is expressed in the milk, then selection would work on the individual’s offspring. If the A1 variant had an adverse effect on calves drinking it, those calves would be less likely to survive and reproduce – so their parent’s genes would not be passed on. If it benefited the calves’ health in some way, then the allele would be selected for (through enhanced survival and reproduction of the calves. A third possibility is that the mutation is neutral, in which case its frequency in the population could be affected by genetic drift, or through its being linked to another, beneficial gene. Farming practices (artificial selection) may also affect the allele’s frequency. For example, mating is non-random, with much of the dairy herd inseminated artifically using semen from a relatively small number of bulls.  If some of these bulls carried the A1 allele, its frequency in the population’s gene pool could increase relatively quickly.  So both natural and artifical selection may have led to evolution: a change in allele frequency in the gene pool of our dairy herds.

K. Woodward (2004) A2 milk and farmer decisions – retrieved as a pdf on 01 June 2008. This document discusses the role of selective breeding (artificial selection) in altering the gene pool of our dairy herd.

5 thoughts on “population genetics of A1 & A2 milk”

  • For people, it is believed that the A1 variant poses health risks on the human drinker. Could the A1 variant have the same deleterious effect on calves? Maybe not because if it did, the A1 allele could not have persisted in the population. Perhaps the mutation in the A2 allele leading to the A1 allele is a neutral one such that there was random genetic drift that allowed it to persist in the population. Am I right?

    • Given that dairy calves in NZ are reared off their mothers and generally feed milk that comes from the herd or less commonly milk powder, it would seem likely that they would receive a mixture of A1 and A2 milk so difficult to tell if there is some negative effect

  • Could A1 mutation occur as a protective mechanism for the cows since they’ve been domesticated by humans? For example, a factor that only harms people and not their own cow members? Or further, could it have something to do with possible feed/diet changes as they probably no longer just eat grass as people start to raise them?

    • For example, a factor that only harms people and not their own cow members? – highly unlikely as any selection pressure wouldn’t be acting on the cows, which is where the mutation would be.
      Remember that mutations don’t “occur as a protective mechanism”; they are random & will only become widespread in a population if there’s a selective advantage to them.

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