Gene duplication

Studies of the evolution of DNA and protein sequences have generally concentrated on changes arising through point mutations of individual nucleotide bases. Indeed, molecular evolution has often been portrayed essentially as the progressive accumulation of point mutations in genes. However, evolution of DNA can also take place in other ways. One of the most important changes that can occur is tandem duplication of genes. This arises through slippage during the replication of DNA during cell division. Once a gene has been duplicated, the way is open for divergent evolution of the original and its copy. Indeed, over long periods of evolutionary time, gene duplication can occur repeatedly, such that quite large families of genes can result. A prime example is provided by globin genes, which are thought to have arisen from an original single gene through repeated duplication. The hemoglobin molecule, which plays a vital role in respiration, consists of four globin chains. In the blood of adult humans, the hemoglobin molecule contains two alpha-chains and two beta-chains. Sequence comparisons indicate that the beta-chain arose from the alpha-chain through an ancient duplication. There are also special hemoglobins that are temporarily present during the embryonic and fetal stages. Embryonic hemoglobin contains two epsilon-chains, while fetal hemoglobin contains two gamma chains. Both the epsilon-chains and the gamma chains also arose from the beta-chain through relatively recent duplications that took place during the evolutionary radiation of the placental mammals. This illustrates how gene duplication can provide an alternative route for the evolution of new functional properties of genes.

During the long history of evolution of living organisms with a cell nucleus containing chromosomes (eukaryotes), there have also been cases where the entire set of chromosomes has been multiplied (ploidy), for example through doubling of their number. Once sex chromosomes became established, as is the case with all living mammals (XX for females and XY for males), such doubling of the entire set of chromosomes became virtually impossible. Doubling of a male set of chromosomes (to XXYY) would result in the presence of two X chromosomes, thus disrupting the normal process of sex determination in which males have only a single X chromosome. However, at an earlier stage of evolution,

A mounted specimen of the now-extinct thylacine, or Tasmanian wolf (Thylacinus cynocephalus). (Photo by Tom McHugh/Photo Researchers, Inc. Reproduced by permission.)

prior to the development of typical mammalian sex chromosomes, multiplication of chromosome sets would still have been possible. Although the evidence is controversial, there is a strong possibility that two successive duplications of the entire chromosome set took place during vertebrate evolution leading up to the emergence of the mammals. For example, two successive doublings of an original set of 12 chromosomes could have let to a set of 48 chromosomes, which is the modal condition found in placental mammals. Although duplications of an entire chromosome set can, of course, be subsequently masked by secondary modifications of individual chromosomes, quadrupling of the chromosomes prior to the emergence of the ancestral placental mammals should still be reflected in the presence of four copies of many individual genes. This does, indeed, seem to be the case for many sets of genes, such as the homeobox genes that play an important part in development.

Duplication of individual genes or entire chromosomes in fact poses an additional problem for reconstruction of phylo-genetic trees using molecular data sets. When a tree is based on nucleotide sequences for any individual gene, care must be taken to ensure that it is really the same gene that is being compared between species. If there are multiple copies of a particular gene in the genome, there is always the danger that comparisons between species might involve different copies. A striking example of this danger is provided by mi-tochondrial genes. Although gene duplication has never been recorded within the mitochondrial genome, individual mito-chondrial genes have been repeatedly copied into the nuclear genome, where they generally remain functionless. Inadvertent inclusion of such redundant nuclear copies in comparisons of mitochondrial genes between species has led to serious errors in interpretation. For instance, a supposed mi-tochondrial gene sequence reported for a dinosaur turned out to be an aberrant nuclear copy of that sequence in human DNA.

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