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

HOW GENOMES EVOLVE
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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.
single-chain globin binds
one oxygen molecule
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.
oxygenbinding
site
on heme
β
EVOLUTION OF A
SECOND GLOBIN
CHAIN BY
GENE DUPLICATION
FOLLOWED BY
MUTATION
β
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 α- and 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 α 2 β 2 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.
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
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 α 2 ε 2 ) than the fetal γ chain,
which forms α 2 γ 2 . 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 (α 2 δ 2 ) 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.
millions of years ago
α
four-chain globin binds four
oxygen molecules in a
cooperative manner
chromosome
16
100
300
500
700
chromosome
11
various
a genes e g G g A
MBoC6 m4.86/4.74
d b
fetal
b
a
translocation
separating a
and b genes
b
single-chain
globin
α
adult
b
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 γ G and γ A , 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.