“…Apparently, neither the V H H hallmark amino acids, nor the presence of a long CDR3 loop of 24 aa, caused folding problems (43). Nevertheless, the genomic organization of the V H H genes (i.e., promoter, leader signal, intron, V-exon, and recombination signal sequence) is otherwise remarkably similar to that of the conventional V H counterparts (44). It has been reasoned that V H H genes have recently evolved from conventional V H genes after the emergence of the Tylopoda (Ͼ50 million years ago), which makes it likely that both types are accommodated in the V gene cluster of the H chain locus (44).…”