Chemistry Reference
In-Depth Information
evolution. An example of this issue has been presented in Chapters 17 and 19 for
the hevein-like domain in plants and animals. As already discussed, case studies
of the molecular mechanisms for carbohydrate binding and specifi city indicate
that similar 'solutions' have likely been found several times by evolution.
•
Evolutionary diversifi cation of function of CTLDcps has occurred by both genetic
and regulatory mechanisms, consistent with the classic theory of Ohta [15].
There are examples showing gene duplication within groups, recombination
events leading to new groups and mutational adaptation of CTLDs, but also
development of regulation of expression of CTLDcps genes.
We will illustrate the last point with some examples. In higher vertebrates the
fi rst mechanism is particularly common in the adaptive immune system gene
families in groups II and V, which constitute a signifi cant proportion of vertebrate
CTLDcps (30 or 45%). These proteins bind carbohydrate or protein or both. Most
group II and V genes are clustered on the chromosomes, including mixed clusters
of group II and V genes. For details of these immune receptors, see Chapters 19
and 27. These clusters clearly result from gene duplication with subsequent diver-
gence of the CTLD sequence to provide varied ligand- binding specifi city. An
example is illustrated in Figure 20.6 for the SIGNR proteins in mouse; the number
of genes is greatly expanded compared with human [16]. For information on the
structure and function of DC - SIGN see Figure 16.1 i and Chapters 19 and 25 .
An example of gene recombination events in vertebrates is well demonstrated
by CTLDcps with clade- specifi c functions, such as snake venoms, bird egg-shell
proteins and fi sh antifreeze proteins. Figure 20.7 presents a phylogenetic recon-
struction of the evolutionary history of the CTLDs of selected vertebrate groups
which allows us to see the likely origin of the clade- specifi c CTLDs [2] . The CTLD
of the only carbohydrate-binding snake venom class most resembles those of the
Reg proteins of group VII. An example involving both genetic and regulatory evo-
lution is given in Info Box 1 .
Info Box 1
An intriguing example of both genetic and regulatory evolution is provided by
the recent reanalysis by Schulenberg
et al.
of
C. elegans
CTLDcps, now num-
bered at 278. Most of these CLTDcp genes are found in clusters resulting from
gene duplications, an interpretation supported by phylogenetic analysis of the
CTLDs. It has been found that the nematode is able to mount a distinct defense
response towards different pathogens (that is a
specifi c
innate immune re-
sponse). Much of this is attributed to pathogen-induced CTLDcps; 61 of them
or 22% of the total can be upregulated but very few by more than two pathogens.
The majority (74%) are secreted proteins and it is thought that they may act
not only in pathogen recognition, but as opsonizing factors. It appears that the
large set of CTLDcps are key players in an intricate innate immune system built
by evolution in
C. elegans
.
