Still later, during the evolution of mammals, the β-chain gene apparently underwent duplication and mutation to give rise to a second β-like chain that millions of years ago is synthesized specifically in the fetus. The resulting hemoglobin molecule has a higher affinity for oxygen than adult hemoglobin and thus helps in the transfer of oxygen from the mother to the fetus. The gene for the new β-like chain subsequently duplicated and mutated again to produce two new genes, ε and γ, the ε chain being produced earlier in development (to form α2ε2) than the fetal γ chain, which forms α2γ2. A duplication of the adult β-chain gene occurred still later, during primate evolution, to give rise to a δ-globin gene and thus to a minor form of hemoglobin (α2δ2) that is found only in adult primates (Figure 4–76).
Each of these duplicated genes has been modified by point mutations that affect the properties of the final hemoglobin molecule, as well as by changes in regulatory regions that determine the timing and level of expression of the gene.
Figure 4–76 An evolutionary scheme for the globin chains that carry oxygen in the blood of animals. The scheme emphasizes the β-like globin gene family. A relatively recent gene duplication of the γ-chain gene produced γg and γA, which are fetal β-like chains of identical function. The location of the globin genes in the human genome is shown at the top of the figure.
As a result, each globin is made in different amounts at different times of human development.
The history of these gene duplications is reflected in the arrangement of hemoglobin genes in the genome. In the human genome, the genes that arose from the original β gene are arranged as a series of homologous DNA sequences located within 50,000 nucleotide pairs of one another on a single chromosome. A similar cluster of human α-globin genes is located on a separate chromosome. Not only other mammals, but birds too have their αand β-globin gene clusters on separate chromosomes. In the frog Xenopus, however, they are together, suggesting that a chromosome translocation event in the lineage of birds and mammals separated the two gene clusters about 300 million years ago, soon after our ancestors diverged from amphibians (see Figure 4–76).
There are several duplicated globin DNA sequences in the αand β-globin gene clusters that are not functional genes but pseudogenes. These have a close sequence similarity to the functional genes but have been disabled by mutations that prevent their expression as functional proteins. The existence of such pseudogenes makes it clear that, as expected, not every DNA duplication leads to a new functional gene.
genes Encoding New Proteins Can be Created by the Recombination of Exons
The role of DNA duplication in evolution is not confined to the expansion of gene families. It can also act on a smaller scale to create single genes by stringing together short duplicated segments of DNA. The proteins encoded by genes generated in this way can be recognized by the presence of repeating similar protein domains, which are covalently linked to one another in series. The immunoglobulins (Figure 4–77), for example, as well as most fibrous proteins (such as collagens) are encoded by genes that have evolved by repeated duplications of a primordial DNA sequence.
In genes that have evolved in this way, as well as in many other genes, each separate exon often encodes an individual protein folding unit, or domain. It is believed that the organization of DNA coding sequences as a series of such exons separated by long introns has greatly facilitated the evolution of new proteins. The duplications necessary to form a single gene coding for a protein with repeating domains, for example, can easily occur by breaking and rejoining the DNA anywhere in the long introns on either side of an exon; without introns there would be only a few sites in the original gene at which a recombinational exchange between DNA molecules could duplicate the domain and not disrupt it. By enabling the duplication to occur by recombination at many potential sites rather than just a few, introns increase the probability of a favorable duplication event.