Biology Reference
In-Depth Information
orthologous genes and provide abundant evidence for a neutralist model of evolu-
tion. Nucleotide substitutions resulting in human genetic disease (Cooper and
Krawczak, 1993) may be taken as representative examples of negative (purifying)
selection since many of the lesions that have come to clinical attention are likely
to reduce (or would once have reduced) survival and/or reproductive fitness. By
contrast, unequivocal examples of the positive Darwinian selection of
nucleotide/amino acid substitutions in higher eukaryotes are much rarer. Indeed,
there are relatively few examples of single base-pair substitutions that have
occurred within the coding regions of mammalian genes during evolution which
have been sufficiently well characterized for us to be able to identify the conse-
quent change in protein structure and function that has been subject to positive
selection. Several illustrative examples are discussed below. Since these systems
have not so far been fully characterized, further studies are eagerly awaited.
The visual pigments.
The visual pigments, which comprise an integral mem-
brane protein (opsin) coupled to a light-sensitive chromophore, are spectrally
tuned to a particular wavelength of maximal absorption,
max. The visual pig-
ments in rods (photoreceptor cells that function in dim light) are rhodopsins
which have a
max of 495 nm. In cones, the photoreceptor cells that mediate
colour vision, there are three types of visual pigment which in humans have
max
values of 420 nm (blue/short wavelength-sensitive), 530 nm (green/middle wave-
length-sensitive) and 560 nm (red/long wavelength-sensitive). The human genes
encoding these opsins are: rhodopsin (
RHO
; 3q21-q24), the blue cone pigment
(
BCP
; 7q31-q35), the green cone pigment (
GCP
; Xq28) and red cone pigment
(
RCP
; Xq28). These genes have evolved by a process of duplication and diver-
gence from a common ancestor ~500 Myrs ago (Yokoyama, 1997) and encode pro-
teins that harbour specific amino acid changes that are directly responsible for the
shifts in
max values between the different visual pigments.
To understand the molecular basis of spectral tuning of visual pigments, it is
necessary to correlate the sequences of the visual pigments with their
max val-
ues. Such an analysis was first performed by Yokoyama and Yokoyama (1990) who
compared the red and green visual pigments from human and the Mexican cave-
fish,
Astyanax fasciatus
. The red pigments in humans and cavefish were found to
have evolved from the green pigments
independently
by three specific amino acid
changes (Ala180Ser, Phe277Tyr and Ala285Thr, i.e. AFA SYT;
Figure 7.2
). A sim-
ilar study in primates (Neitz
et al
., 1991) also concluded that the spectral differ-
ence between red and green pigments could be accounted for by the difference
between AFA (green) and SYT (red). These three critical amino acid residues are
located near the chromophore and their experimental substitution has been
shown to alter
max values not only in human red and green pigments (Asenjo
et
al
., 1994) but also in bovine rhodopsin (Chan
et al
., 1992).
Most mammals have dichromatic vision, possessing blue visual pigments
together with either red or green pigments (Jacobs, 1993). Phylogenetic analysis
of a range of vertebrates has suggested that the vertebrate ancestor of the opsin
gene was a green pigment gene encoding AFA at the three critical sites and that
the common ancestor of tetrapods acquired a red pigment by two amino acid sub-
stitutions (Phe277Tyr and Ala285Thr;
Figure 7.2
). The SYT of the red pigments
