Genes and Chromosomes

The recognition that genes occupy characteristic positions on chromosomes and are segregated by meiosis enabled Mendel’s successors to provide a physical explanation for his model of inheritance. It soon became apparent that the association of genes with chromosomes has other genetic consequences as well. We mentioned above that genes located on the same chromosome may not follow Mendel’s law of independent assortment. What is the pattern of inheritance of such genes? How do we determine where genes are located on a chromosome and the distances between them? The answers to these and many other genetic questions were worked out in studies of the fruit fly Drosophila melanogaster. Its small size, its ease of cultivation, and its short generation time made this animal an attractive experimental subject. Beginning in 1909, Thomas Hunt Morgan and his students pioneered the study of Drosophila in Columbia University’s famous “fly room” where they discovered the phenomena described in this section. Drosophila remains extremely important in studies of chromosome structure, population genetics, the genetics of development and the genetics of behavior.

Genes on the same chromosome are linked

Some of the crosses Morgan performed with fruit flies resulted in phenotypic ratios that were not in accord with those predicted by Mendel’s law of independent assortment. Morgan crossed Drosophila of two known genotypes, BbVgvg X bbvgvg, for two different characters, body color and wing shape:

B (wild-type gray body), is dominant over b (black body)

Vg (wild-type wing) is dominant over vg (vestigial, a very small wing)

Morgan expected to see four phenotypes in a ratio of 1:1:1:1, but that is not what he observed. The body color gene and the wing size gene were not assorting independently; rather, they were for the most part inherited together. These results became understandable to Morgan when he assumed that the two loci are on the same chromosome— that is, that they are linked. After all, since the number of genes in a cell far exceeds the number of chromosomes, each chromosome must contain many genes. The full set of loci on a given chromosome constitutes a linkage group. The number of linkage groups in a species equals the number of homologous chromosome pairs. Suppose, now, that the Bb and Vgvg loci are indeed located on the same chromosome. Why, then, didn’t all of Morgan’s F1 flies have the parental phenotypes—that is, why did his cross result in anything other than gray flies with normal wings (wild-type) and black flies with vestigial wings? If we assumed that linkage is absolute — that is, that chromosomes always remain intact and unchanged — we would expect to see just those two types of progeny. However, this is not always what happens.

Genes can be exchanged between chromatids

Absolute linkage is extremely rare. If linkage were absolute, Mendel’s law of independent assortment would apply only to loci on different chromosomes. What actually happens is more complex and therefore more interesting. Chromosomes are not unbreakable, so recombination of genes can occur. That is, genes at different loci on the same chromosome do sometimes separate from one another during meiosis. Genes may recombine when two homologous chromosomes physically exchange corresponding segments during prophase I of meiosis — that is, by crossing over. Recall from Chapter 9 that the DNA is replicated during the S phase, so that by prophase I when homologous chromosome pairs come together to form tetrads, each chromosome consists of two chromatids. The exchange event involves only two of the four chromatids in a tetrad, one from each member of the homologous pair, and can occur at any point along the length of the chromosome. The chromosome segments involved are exchanged reciprocally, so both chromatids involved in crossing over become recombinant (that is, each chromatid ends up with genes from both of the organism’s parents). Usually several exchange events occur along the length of each homologous pair.

When crossing over takes place between two linked genes, not all progeny of a cross will have the parental phenotypes. Instead, recombinant offspring appear as well, as they did in Morgan’s cross. They appear in proportions called recombinant frequencies, which are calculated by dividing the number of recombinant progeny by the total number of progeny. Recombinant frequencies will be greater for loci that are farther apart on the chromosome than for loci that are closer together, because an exchange event is more likely to occur between genes that are far apart than between genes that are close together.

Geneticists can make maps of chromosomes

If two loci are very close together on a chromosome, the odds of crossing over between them are small. In contrast, if two loci are far apart, crossing over could occur between them at many points. In a population of cells undergoing meiosis, a greater proportion of the cells will undergo recombination between two loci that are far apart than between two loci that are close together. In 1911, Alfred Sturtevant, then an undergraduate student in T. H. Morgan’s fly room, realized how that simple insight could be used to show where different genes lie on a chromosome in relation to one another. The Morgan group had determined recombinant frequencies for many pairs of linked genes. Sturtevant used these recombinant frequencies to create genetic mapsthat showed the arrangement of genes along the chromosome. Ever since Sturtevant demonstrated this method, geneticists have mapped the chromosomes of eukaryotes, prokaryotes, and viruses, assigning distances between genes in map units. A map unit corresponds to a recombinant frequency of 0.01; it is also referred to as a centimorgan (cM), in honor of the founder of the fly room. You too, can work out a genetic map.