Some genes have more than two alleles, and then the pattern of inheritance is a little more complex. We call this situation multiple allele inheritance. However, the basic rules are just the same – alleles can be dominant or recessive or codominant.
An example of multiple allele inheritance occurs in the inheritance of the ABO blood groups. This is an interesting example as it also involves codominance. In the ABO blood grouping system, there are four blood groups, determined by the presence or absence of two antigens (A and B) on the surface of the red blood cells.
Although the gene may have more than two alleles, because they are alleles of the same gene, any individual will still only have a maximum of two of the alleles. This is because the different alleles are found at the same locus (position) on homologous chromosomes. Because there are only two copies of each chromosome, the person can only have two alleles of the gene.
There are three alleles involved in the inheritance of these blood groups:
• IA, which determines the production of the A antigen
• IB, which determines the production of the B antigen
• IO, which determines that neither antigen is produced
What is the physical basis for these patterns of inheritance?
We began this chapter by pointing out that a gene is a part of a chromosome. To understand the patterns of inheritance we have discussed so far, we must look at how chromosomes behave when gametes are formed. For gametes to be formed, special cells in the sex organs of the organism divide by a process known as meiosis. When a cell divides in this manner, there are three key outcomes:
• it produces four ‘daughter’ cells
• these daughter cells have only half the number of chromosomes of the original cell; they have one chromosome from each homologous pair
• the daughter cells show genetic variation
To understand how this happens we need to look at the stages of meiosis. First, if you think carefully, a cell does not normally divide to produce four cells – it produces two. Therefore, meiosis must entail two divisions. We call these meiosis I and meiosis II. Let us fist gain some kind of overview of meiosis, by looking at how just one pair of homologous chromosomes behaves through the two divisions. At the start of the process, each chromosome is a double structure; it is made of two chromatids held together by a centromere. This is because the DNA in each chromosome replicated prior to meiosis commencing. Before any division takes place, chromatids from different chromosomes in the homologous pair undergo ‘crossing over’. In this process, they exchange sections of DNA. After this has taken place, meiosis I follows and the two chromosomes that make up the pair are separated into different cells. In meiosis II, the two chromatids that make up each chromosome are separated into separate cells. Notice that, because of crossing over, none of these chromatids are the same. Look at the combinations of alleles on the chromosomes at the start and at the end. There is genetic variation in the daughter cells, which also have only half the original chromosome number – they are said to have the haploid number of chromosomes, unlike the parent cell which had the diploid number of chromosomes.
During meiosis, the following things happen to the chromosomes:
• They duplicate; the DNA in each chromosome makes an exact copy of itself and histones associate with it to make another chromosome. The original and the copy remain attached by a centromere and are called not chromosomes but chromatids.
• They ‘condense’; when chromosomes are not involved in cell division, they are very long and thin and all the genes can be active. However, they cannot be moved around a cell in this form, so they become much shorter and fatter.
• The chromosomes of a homologous pair (each one by now duplicated) ‘find’ each other (this is called synapsis and no one is quite sure how it happens) and form a bivalent.
• Whilst associated in the bivalent, chromatids from different chromosomes undergo crossing over. These chromatids are called non-sister chromatids; the chromatids that make up one chromosome are sister chromatids. In this process, the chromatids exchange equivalent sections of DNA, and all four chromatids in the homologous pair are genetically different
• The chromosomes (or chromatids) are moved around the cell by fires that make up a spindle.
• This is achieved by the spindle fires contracting and pulling the chromosomes/chromatids. In the two divisions of meiosis, the chromosomes attach to the spindles differently so that:
– in meiosis I, whole chromosomes are moved and the chromosomes that make up a homologous pair are separated
– in meiosis II, the chromatids that make up each chromosome are separated.
It is pure chance how bivalent arrange themselves at metaphase 1. With just two bivalent, there are two possible arrangements and two different sets of gametes. With 23 pairs of chromosomes, there are 222 different combinations. Each bivalent aligns itself independently of the others. This is called independent assortment and is an important source of genetic variation in the gametes produced by meiosis. It explains why alleles of two different genes behave in the way they do in a dihybrid cross.