STRUCTURAL REPERTOIRE IN VH PSEUDOGENES OF IMMUNOGLOBULINS - COMPARISON WITH HUMAN GERMLINE GENES AND HUMAN AMINO-ACID-SEQUENCES

In the pool of human immunoglobulin V-H gene segments, pseudogenes amo unt to roughly 30% of the total number of genes. Some of them are high ly conserved among unrelated individuals. These facts suggest a possib le functional role for pseudogenes in the human immune response divers ity This paper intends to provide additional information about the str ucture of V-H pseudogene sequences to evaluate the possible role of ps eudogenes in the immune response. Mutations capable of altering framew ork stability in human V-H pseudogenes were analyzed. Results indicate that V-H pseudogenes are about 14 times as divergent as human V-H fun ctional germline genes on the one hand, and four times as divergent in the case of human V-H amino acid sequences on the other. The high num ber of disruptive mutations in pseudogenes is an expected result becau se of the lack of functionality of these genes. In the second part of the work we analyze whether or not the same takes place in the positio ns that determine the existence of canonical structures in the hyperva riable loops in V-H pseudogenes. An extension of such analysis is appl ied to all species with reported V-H pseudogenes. In contrast with res ults concerning framework positions, 69% of known human V-H pseudogene s have canonical structures in the first hypervariable loop, while 48% do so in the second one. Comparison of these results with those found in human V-H functional germline genes and human V-H amino acid seque nces shows that in the former as many as 100% and in the latter 96% ha ve canonical structures. In V-H amino acid sequences the result is sim ilar to pseudogenes for H1. For H2, such value lies between the percen tage of germline genes (96%) and the percentage of pseudogenes (48%). The possible significance of the existence of canonical structures in the hypervariable loops of V-H pseudogenes is discussed.