Evolution of immunoglobulin light chains: cDNA clones specifying sandbar shark constant regions.
Sharks are living fossils that are indistinguishable morphologically from their Devonian ancestors of approximately equal to 400 million years ago. If parallel conservatism characterizes their biochemical evolution, characterization of their immunoglobulin chains could provide information regarding the primordial features of these essential defense molecules. Shark immunoglobulins are polydisperse like those of mammals, but these species lack homogeneous myeloma proteins. This heterogeneity has precluded direct determination of the sequence of elasmobranch light-chain proteins. We have sequenced four cDNA clones that contain the constant-region sequence as well as varying degrees of variable- or joining-region segments. The sandbar shark (Carcharhinus plumbeus) has at least four distinct light-chain constant regions, and these can be considered homologs of mammalian lambda chains. Approximately 40% identity was found in comparison from sharks to mammals. Certain stretches of sequence were remarkably conserved, whereas others varied in a manner consistent with accepted concepts of speciation. One hexapeptide (Ala-Thr-Leu-Val-Cys-Leu) occurred in lambda constant regions of all vertebrate species. There was a universal conservation of certain cysteines, phenylalanines, tryptophans, and glycines and strong identities in the block of residues from Ser-176 to Trp-186. Comparison of the shark sequence with that of the characterized human lambda myeloma protein Mcg indicates a strong conservation of three-dimensional structure in this light-chain domain representing species whose ancestors diverged early in vertebrate evolution. The shark light-chain sequence contains primordial features shared by mammalian kappa and lambda chains and by T-cell receptor beta chains.
Schluter
S F
SF
Department of Microbiology and Immunology, University of Arizona, College of Medicine, Tucson 85724.
Hohman
V S
VS
Edmundson
A B
AB
Marchalonis
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002645:Chickens; D003001:Cloning, Molecular; D003429:Cross Reactions; D004247:DNA / Q000235:genetics; D005580:Fossils; D015723:Gene Library; D005803:Genes, Immunoglobulin; D007106:Immune Sera; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D051379:Mice; D008961:Models, Structural; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D012754:Sharks / Q000235:genetics* / Q000276:immunology
D007106:Immune Sera; D007127:Immunoglobulin Constant Regions; D007147:Immunoglobulin Light Chains; D011947:Receptors, Antigen, B-Cell; D004247:DNA