The Organization, Expression, and Evolution of Antibody Genes and Other Multigene Families

Abstract

The multigene family is a unit of chromosomal organization. Its gene members are closely linked, homologous in sequence, and have overlapping functions. Multigene families can be divided into three catagories: simple-sequence, multiplicational, and informational-by a variety of structural and functional criteria. Multigene families exhibit two novel evolutionary features-coincidental evolution and rapid change in family size-that suggest that they all share one or more evolutionary mechanisms. Natural selection cannot act directly upon individual genes in a family because of their identical or overlapping functions; hence selection must operate upon the family as a whole or upon blocks of genes within the family. The mechanism(s) for coincidental evolution expands out variant genes within a family so they can be acted upon by natural selection and, accordingly, permits multigene families to evolve adaptively. The control mechanisms in multiplicational families appear to promote the rapid expression of many gene copies. In contrast, the regulatory mechanisms of informational families promote the selection, expression, and amplification of appropriate units of information. The close linkage of the genes in a family appears to be a consequence of the fact that their control and evolutionary mechanisms may only operate on tandemly linked genes. New multigene families may evolve from a single gene or from other multigene families. In addition to evolving new functions, the latter mode of evolution generates a new multigene family whose members are preadapted to interact with those of the old family. These family interactions can lead to the evolution of more sophisticated molecular machines or to the regulation of one family by a second. Multigene families may be large or small. The three catagories of multigene families allow potential multigene families to be identified, and they suggest specific experimental approaches for the study of new families. Some of the most interesting genetic systems under the investigation today are known or potential informational multigene families. This is not fortuitous in that many of the most interesting aspects of phenotype are complex ones with correspondingly complex genetic, evolutionary, and regulatory requirements. One of the frontiers in modern genetics is the identification, characterization, and understanding of informational multigene families.

On the location of palindromes in immunoglobulin genes.

“…The gene expansion hypothesis (32) does not explain the diversity of hypervariable segments after rapid gene expansion when a new set of genes, identical to one member of the old set, appears. The palindromic structures that are also preferred sites for recombination (31) could promote exchange of hypervariable segments between the new and old gene sets.…”

“…The palindromic structures that are also preferred sites for recombination (31) could promote exchange of hypervariable segments between the new and old gene sets. This can conserve variability during V gene expansion (32) and may also explain the sharing of similar hypervariable regions by antibodies of different framework sequences (30).…”

Multiple VH gene segments encode murine antistreptococcal antibodies.

“…Unequal recombination events can be expected to result in expansion and contraction of this family over time (46), and indeed the BALB/ c genome includes two copies of the V~GAC gene that is apparently present in only a single copy in A/J and C57BL/6 mice (Fig. 5).…”

Structure and evolution of transplantation antigens: partial amino-acid sequences of H-2K and H-2D alloantigens.

“…It will be interesting to determine whether these multigene families share strategies for information storage, information expression and information evolution similar to those seen in the antibody gene families (see ref. 34). …”