Identification of the 48-base-long primordial building block sequence of mouse immunoglobulin variable region genes.

Mouse immunoglobulin heavy-chain variable region (Ig VH) genes apparently arose from the approximately 600-base-pair-long (approximately 12 tandem repeats of the 48-base-pair-long primordial building block sequence TTC-AGC-AGC-CTG-ACT-GGA-TAT-GAC-CTG-GAG-TGG-ACT-TAC-TGC-GCA-AGA) that in the original reading frame specified the amino acid sequence Phe-Ser-Ser-Leu-Thr-Gly-Tyr-Asp-Leu-Glu-Trp-Thr-Tyr-Cys-Ala-Arg. The previously identified, shorter prototype building blocks merely represented particular portions of the above primordial sequence. Even today, the direct descendant in toto of this primordial sequence specifies the last one-sixth of each VH coding sequence: the 83rd to 98th amino acid residues. Furthermore, its four truncated derivatives specify the 4th to 14th, 17th to 23rd, 29th to 37th, and 38th to 48th amino acid residues. Accordingly, all three relatively invariant--therefore, conserved--framework regions (FW-1, FW-2, and FW-3) of VHs are specified by recognizable--therefore, conserved--descendants of the primordial sequence.