Analysis of the genome of the zebrafish, in which at least one whole-genome duplication is thought to have occurred hundreds of millions of years ago, has cast some light on the process of gene duplication and divergence. Although many duplicates of zebrafish genes appear to have been lost by mutation, a significant fraction—perhaps as many as 30–50%—have diverged functionally while both
Figure 4–75 A comparison of the structure of one-chain and four-chain globins. The four-chain globin shown is hemoglobin, which is a complex of two α-globin and two β-globin chains. The one-chain globin present in some primitive vertebrates represents an intermediate in the evolution of the four-chain globin. with oxygen bound it exists as a monomer; without oxygen it dimerizes.
copies have remained active. In many cases, the most obvious functional difference between the duplicated genes is that they are expressed in different tissues or at different stages of development. One attractive theory to explain such an end result imagines that different, mildly deleterious mutations occur quickly in both copies of a duplicated gene set. For example, one copy might lose expression in a particular tissue as a result of a regulatory mutation, while the other copy loses expression in a second tissue. Following such an occurrence, both gene copies would be required to provide the full range of functions that were once supplied by a single gene; hence, both copies would now be protected from loss through inactivating mutations. Over a longer period, each copy could then undergo further changes through which it could acquire new, specialized features.
The Evolution of the globin gene Family Shows How DNA Duplications Contribute to the Evolution of Organisms
The globin gene family provides an especially good example of how DNA duplication generates new proteins, because its evolutionary history has been worked out particularly well. The unmistakable similarities in amino acid sequence and structure among the present-day globins indicate that they all must derive from a common ancestral gene, even though some are now encoded by widely separated genes in the mammalian genome.
We can reconstruct some of the past events that produced the various types of oxygen-carrying hemoglobin molecules by considering the different forms of the protein in organisms at different positions on the tree of life. A molecule like hemoglobin was necessary to allow multicellular animals to grow to a large size, since large animals cannot simply rely on the diffusion of oxygen through the body surface to oxygenate their tissues adequately. But oxygen plays a vital part in the life of nearly all living organisms, and oxygen-binding proteins homologous to hemoglobin can be recognized even in plants, fungi, and bacteria. In animals, the most primitive oxygen-carrying molecule is a globin polypeptide chain of about 150 amino acids that is found in many marine worms, insects, and primitive fish.
The hemoglobin molecule in more complex vertebrates, however, is composed of two kinds of globin chains. It appears that about 500 million years ago, during the continuing evolution of fish, a series of gene mutations and duplications occurred. These events established two slightly different globin genes in the genome of each individual, coding for αand β-globin chains that associate to form a hemoglobin molecule consisting of two α chains and two β chains (Figure 4–75). The four oxygen-binding sites in the α2β2 molecule interact, allowing a cooperative allosteric change in the molecule as it binds and releases oxygen, which enables hemoglobin to take up and release oxygen more efficiently than the single-chain version.