Friday, November 20, 2015

Different kinds of pseudogenes: Polymorphic pseudogenes

There are three main kinds of pseudogenes: processed pseudogenes, duplicated pseudogenes, and unitary pseudogenes [Different kinds of pseudogenes - are they really pseudogenes?].

There's one sub-category of pseudogenes that deserves mentioning. It's called "polymorphic pseudogenes." These are pseudogenes that have not become fixed in the genome so they exist as an allele along with the functional gene at the same locus. Some defective genes might be detrimental, representing loss-of-function alleles that compromise the survival of the organism. Lots of genes for genetic diseases fall into this category. That's not what we mean by polymorphism. The term usually applies to alleles that have reached substantial frequency in the population so that there's good reason to believe that all alleles are about equal with respect to natural selection.

Polymorphic pseudogenes can be examples of pseudogenes that are caught in the act of replacing the functional gene. This indicates that the functional gene is not under strong selection. For example, a newly formed processed pseudogene can be polymorphic at the insertion site and newly duplicated loci may have some alleles that are still functional and others that are inactive. The fixation of a pseudogene takes a long time.

The most interesting cases are single copy functional genes at a given locus that are segregating with inactive versions of the gene at the same locus. These are pseudogenes that may be on their way to becoming unitary pseduogenes. Of course, in all cases of polymorphic pseudogenes there's always the possibility that the pseudogene allele will be lost by random genetic drift instead of being fixed.

One of the best examples is the human gene for N-acetylaminogalactosyl-transferase on chromosome 9. The normal version of this enzyme attaches a sugar called GalNAc (N-acetylaminogalactose) to proteins on the surface of red blood cells. These are recognized by antibodies as antigen A giving rise to type A blood. A mutation in the coding region of the gene causes the enzyme to transfer galactose (Gal) instead of GalNac and this is recognized by different antibodies giving rise to blood type B.

A third allele of the same gene is an inactive pseudogene that doesn't work at all. This is responsible for O-type blood [ABO Blood Types] [Human ABO Gene] [Genetics of ABO Blood Types].

The O-type allele is a pseudogene. It is present at fairly high frequencies in human populations. In some populations, especially native Americans, the pseudogene has become fixed and all individuals have O-type blood because they are homozygous for the O allele.

There doesn't seem to be any significant selection for different blood types and there don't seem to be detrimental effects associated with the pseudogene. This is a polymorphic pseudogene. They are probably not common but it's hard to tell since it requires sequencing a large number of individual genomes from each species and that's not going to happen.

1 comment :

  1. Thank you for posting this series. I have only a rudimentary understanding of genetics, but I am able to follow most of it.