Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

230 Chapter 4: DNA, Chromosomes, and Genomes
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 α- and 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 α- and 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.
More generally, we know from genome sequences that the various parts of
genes—both their individual exons and their regulatory elements—have served
as modular elements that have been duplicated and moved about the genome
to create the great diversity of living things. Thus, for example, many present-day
proteins are formed as a patchwork of domains from different origins, reflecting
their complex evolutionary history (see Figure 3–17).
Neutral Mutations Often Spread to Become Fixed in a Population,
with a Probability That Depends on Population Size
In comparisons between two species that have diverged from one another by millions
of years, it makes little difference which individuals from each species are
H 2 N
H 2 N
heavy chain
NH 2
NH 2
Figure 4–77 Schematic view of an antibody (immunoglobulin) molecule.
This molecule is a complex of two identical heavy chains and two identical
light chains. Each heavy chain contains four similar, covalently linked
domains, while each light chain contains two such domains. Each domain
is encoded by a separate exon, and all of the exons are thought to have
evolved by the serial duplication of a single ancestral exon.
light chain
HOOC
COOH