Structural repertoire in VH pseudogenes of immunoglobulins: comparison with human germline genes and human amino acid sequences.
In the pool of human immunoglobulin VH gene segments, pseudogenes amount to roughly 30% of the total number of genes. Some of them are highly conserved among unrelated individuals. These facts suggest a possible functional role for pseudogenes in the human immune response diversity. This paper intends to provide additional information about the structure of VH pseudogene sequences to evaluate the possible role of pseudogenes in the immune response. Mutations capable of altering framework stability in human VH pseudogenes were analyzed. Results indicate that VH pseudogenes are about 14 times as divergent as human VH functional germline genes on the one hand, and four times as divergent in the case of human VH amino acid sequences on the other. The high number of disruptive mutations in pseudogenes is an expected result because 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 positions that determine the existence of canonical structures in the hypervariable loops in VH pseudogenes. An extension of such analysis is applied to all species with reported VH pseudogenes. In contrast with results concerning framework positions, 69% of known human VH pseudogenes 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 VH functional germline genes and human VH amino acid sequences shows that in the former as many as 100% and in the latter 96% have canonical structures. In VH amino acid sequences the result is similar to pseudogenes for H1. For H2, such value lies between the percentage of germline genes (96%) and the percentage of pseudogenes (48%). The possible significance of the existence of canonical structures in the hypervariable loops of VH pseudogenes is discussed.
Instituto de Investiciones Biológicas, Universidad Veracruzana, Xalapa Veracruz México.
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E
Vargas-Madrazo
J C
JC
Almagro
F
F
Lara-Ochoa
D000595:Amino Acid Sequence; D000818:Animals; D016208:Databases, Factual; D005803:Genes, Immunoglobulin / Q000235:genetics* / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011544:Pseudogenes / Q000235:genetics* / Q000502:physiology; D016415:Sequence Alignment
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region