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JOHN E. CUSHING
sites. The nonvariant positions of the N-terminal sequences of both L
and H chains appear to be similar among widely diverse organisms,
again suggesting a common origin from an ancestral gene (cf. Wikler
et al., 1969; Putnam, 1969).
The extreme variability of the numerous positions in the N-terminal
region cannot yet be understood in terms of genetic and evolutionary
concepts. If this variability reflects the occurrence of gene mutation, it
is not possible to conceive of the antigenic determinant as a mutator
capable of specificaliy and simultaneously inducing so many mutations
at once and in a way that predetermines how the polypeptides will finally
fold in order to achieve a “fit” complementary to the three-dimensional
structure of the antigen. Similarly, it is difficult to conceive of hereditary
or somatic mutations occurring in advance of contact with an antigen
and waiting for it to come along and select them out of the tremendously
large pool of combinations of such mutations that would have to be
stored and available. Finally, no knowledge exists of any mechanism
whereby amino acid sequences are determined by information introduced (as would be the case with antigen) at levels intermediate to
the nucleic acids and their final polypeptide product or between the
finished protein and its polypeptide subunits. Several ingenious hypotheses suggest ways in which one or another of the above difficulties
might be overcome, but to date no experimental evidence is available
that will decide among them. The biologist, therefore, has a first class
puzzle involving a remarkable evolutionary adaptation that is being
painstakingly resolved. There is every reason to believe that this resolution will provide some very profound insights into the mechanisms of
genetic, embryological, and evolutionary biology. The next section will
show how the study of fish relates to this problem.
E. The Immunoglobulins of Fish
The preceding section has outlined the complex nature of the immunoglobulins. Obivously, the mechanism for the synthesis of these
rnolccules is highly evolved in mammals; and it is of great interest to
understand its evolutionary origins and phylogeny. Comparative studies
on lower vertebrates and invertebrates are now in progress in several
laboratories. It is not the purpose of this chapter to review these in
detail. However, some general comments will help place research on
fish Ig in proper perspective. References for background reading should
include “Phylogeny of Immunity” (R. T. Smith et al., 1966), Good and
Papermaster ( 1964), and the symposium “Defense Reactions in Inverte-
JOHN E. CUSHING
sites. The nonvariant positions of the N-terminal sequences of both L
and H chains appear to be similar among widely diverse organisms,
again suggesting a common origin from an ancestral gene (cf. Wikler
et al., 1969; Putnam, 1969).
The extreme variability of the numerous positions in the N-terminal
region cannot yet be understood in terms of genetic and evolutionary
concepts. If this variability reflects the occurrence of gene mutation, it
is not possible to conceive of the antigenic determinant as a mutator
capable of specificaliy and simultaneously inducing so many mutations
at once and in a way that predetermines how the polypeptides will finally
fold in order to achieve a “fit” complementary to the three-dimensional
structure of the antigen. Similarly, it is difficult to conceive of hereditary
or somatic mutations occurring in advance of contact with an antigen
and waiting for it to come along and select them out of the tremendously
large pool of combinations of such mutations that would have to be
stored and available. Finally, no knowledge exists of any mechanism
whereby amino acid sequences are determined by information introduced (as would be the case with antigen) at levels intermediate to
the nucleic acids and their final polypeptide product or between the
finished protein and its polypeptide subunits. Several ingenious hypotheses suggest ways in which one or another of the above difficulties
might be overcome, but to date no experimental evidence is available
that will decide among them. The biologist, therefore, has a first class
puzzle involving a remarkable evolutionary adaptation that is being
painstakingly resolved. There is every reason to believe that this resolution will provide some very profound insights into the mechanisms of
genetic, embryological, and evolutionary biology. The next section will
show how the study of fish relates to this problem.
E. The Immunoglobulins of Fish
The preceding section has outlined the complex nature of the immunoglobulins. Obivously, the mechanism for the synthesis of these
rnolccules is highly evolved in mammals; and it is of great interest to
understand its evolutionary origins and phylogeny. Comparative studies
on lower vertebrates and invertebrates are now in progress in several
laboratories. It is not the purpose of this chapter to review these in
detail. However, some general comments will help place research on
fish Ig in proper perspective. References for background reading should
include “Phylogeny of Immunity” (R. T. Smith et al., 1966), Good and
Papermaster ( 1964), and the symposium “Defense Reactions in Inverte-