VI.

Gene Linkage and Gene Mapping

Mendel's principle that genes controlling different traits are inherited independently of one another turns out to be true only when the genes occur on different chromosomes. The American geneticist Thomas Hunt Morgan and his co-workers, in an extensive series of experiments using fruit flies (which breed rapidly), showed that genes are arranged on the chromosomes in a linear fashion; and that when genes occur on the same chromosome, they are inherited as a single unit for as long as the chromosome itself remains intact. Genes inherited in this way are said to be linked.

Morgan and his group also found, however, that such linkage is rarely complete. Combinations of alleles characteristic of each parent can become reshuffled among some of their offspring. During meiosis, a pair of homologous chromosomes may exchange material in a process called recombination, or crossing-over. (The effect of crossing-over can be seen under a microscope as an X-shaped joint between the two chromosomes.) Crossovers occur more or less at random along the length of the chromosomes, so the frequency of recombination between two genes depends on their distance from each other on the chromosome. If the genes are relatively far apart, recombinant gametes will be common; if they are relatively close, recombinant gametes will be rare. In the offspring produced by the gametes, the crossovers show up as new combinations of visible traits. The more crossovers that occur, the greater the percentage of offspring that show the new combinations. Consequently, by arranging suitable breeding experiments, scientists can plot, or map, the relative positions of the genes along the chromosome.

In recent years geneticists have used organisms such as bacteria, moulds, and viruses, which rapidly produce extremely large numbers of offspring, to detect recombination events that occur only rarely. Thus, they are able to make maps of genes that are quite close together. The method introduced at Morgan's laboratory has now become so exact that differences occurring within a single gene can be mapped. These maps have shown that not only do the genes occur in linear fashion along the chromosome, but they themselves are linear structures. The detection of rare recombinants can reveal the existence of structures even smaller than those observed through the most powerful microscopes.

Studies of fungi, and more recently of fruit flies, have shown that recombination of alleles can sometimes take place without reciprocal exchanges between chromosomes. Apparently, when two different versions of the same gene occur together (in a heterozygote), one of them may be “corrected” to match the other. Such corrections may take place in either direction (for example, the allele A may be changed to a, or vice versa). This process has been called gene conversion. Occasionally, several adjacent genes may undergo conversion together, and the likelihood of two genes being coconverted is related to their distance apart. This provides another way of mapping the relative positions of genes on the chromosome.

By March 2000, the entire genome (the complete set of genetic information) of the fruit fly had been deciphered and mapped by another, faster method, whole-genome shotgun sequencing, which splits the genome into tiny fragments and uses supercomputers to work out how these fragments would reassemble and, therefore, the sequence of the fly’s genetic blueprint. This was also one of the methods used in the Human Genome Project (also see below).