Molecular Biology and Evolution 19:205-215 (2002)
© 2002 Society for Molecular Biology and Evolution
Adaptive Evolution of Variable Region Genes Encoding an Unusual Type of Immunoglobulin in Camelids
Institute of Molecular Evolutionary Genetics, Department of Biology, The Pennsylvania State University
A typical immunoglobulin (Ig) molecule is composed of four polypeptide chains: two identical heavy (H) chains and two identical light (L) chains. This tetrameric structure is conserved in almost all jawed vertebrate species. However, it has been discovered that camels and llamas (family: Camelidae) possess a type of dimeric Ig that consists of two H chains only. These H chains do not associate with L chains, and they do not have the first constant region (CH1), which is present in the conventional Ig. In spite of these changes, the dimeric Ig maintains the normal immune function. To understand the evolution of the dimeric Ig, we studied the phylogenetic relationships of the variable region (VHH) genes of the dimeric Ig from Camelidae and those (VH) of the conventional Ig from mammals. The results showed that the VHH genes form a monophyletic cluster within one of the mammalian VH groups, group C. We examined the type of selective force in complementarity-determining regions (CDRs) and framework regions (FRs) by comparing the rate of synonymous (dS) and nonsynonymous (dN) substitutions. We found that the results obtained from VHH genes were similar to those from VH genes in that CDRs showed an excess of dN over dS (indicating positive selection), whereas the reverse was true for FRs (purifying selection). However, when the extent of positive selection or purifying selection was investigated at each codon site, three major differences between VHH and VH genes were found. That is, very different types of selective force were observed between VHH and VH genes (1) at the sites that contact the L chain in the conventional Ig, (2) at the sites that interact with the CH1 region in the conventional Ig, and (3) in the H1 loop. Our findings suggest that adaptive evolution has occurred in the functionally important sites of the VHH genes to maintain the normal immune function in the dimeric Ig.
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