Multiple variants of a gene - In many cases complete variants of genes for the same type of protein are found, to be expressed in different tissues or at different stages in development. Examples include the embryonic ( and ), fetal ( and ), and adult (, , and ) globins of mammals. For each of these proteins there exists a complete gene in every cell of the mammal.

Figure 7.23 depicts the clusters of genes for the and classes of hemoglobins in humans. Each of these genes has the kind of exon--intron structure shown in Figure 7.20. That is, the genes are separated by long stretches of nontranscribed DNA. Some portions of these intervening regions contain control signals, accounting for the globin genes' complex and subtle regulation.

1. Although the globin gene clusters are found in all human cells, they are expressed only in the erythropoietic cells, cells that give rise to red blood cells.

2. Expression of each globin variant is strictly constrained to certain developmental stages. In the early embryo, only the and genes are transcribed; all other globin genes are turned off. As development proceeds, transcription switches to the fetal and genes. Then, at about the time of birth the adult variant begins to dominate and transcription of ceases (see Figure 7.22).

This kind of developmental regulation is peculiar to eukaryotes--no prokaryote needs such a mechanism. One reason may be that the use of multiple variant genes is expensive--the human genome devotes about 100,000 bp of DNA to produce different variants of hemoglobin.

Many other gene families exist. Some seem to play developmental roles. Others appear to exist in multiple forms in order to satisfy a multiplicity of similar but distinct needs. In each case, it seems likely that the members of a particular gene family have evolved by successive duplications of an original, ancestral gene.

Pseudogenes - Gene families often include one or more pseudogenes, or nonfunctional genes. Pseudogenes can be recognized because they bear strong sequence similarity to functioning genes, from which they undoubtedly evolved. They are no longer transcribed, however, because some element required for transcription (often a flanking control region or promoter) is missing or defective. Because their sequences are not expressed, pseudogenes are no longer under strong selective control in evolution. As a consequence they accumulate mutations that would be selected against in functional genes. This phenomenon provides at least the possibility that novel genes may arise from pseudogenes that become transcribable again. Examples of pseudogenes can be seen in Figure 7.23.

A number of quite different explanations combine to account for the very large size of the genomes of eukaryotic organisms. At the same time, it is difficult to rationalize the extreme variations in the amount of DNA that are sometimes observed even between closely related organisms.

1. Genome Organization

2. Multigene Families and Pseudogenes

3. Eukaryotic Multigene Families

4. Globin Gene Server