Hypervariation in B-cells as an evolutionary model

Pentcho Valev RUMYM at BGEARN.ACAD.BG
Fri Jan 23 11:08:35 EST 1998


Rumy (RUMYM at OBZOR.BIO21.ACAD.BG) wrote:>>>>>>>>>>>>>>>>>>
Hypermutations occuring in the hypervariable regions (CDRs) of rearranged
immunoglobulin genes can also be regarded as "directed mutations". These
somatic mutations are triggered by binding of an antigen to the
corresponding antibody producing cell. Mutations in this case affect
predominantly those portions of the immunoglobulin genes which code for
antigen binding sites. As a result antibodies with higher affinity and
specificity of binding to the cognate antigen are generated. It is very
tempting to see Lamarcian evolution in this process. But what is still
required for defining them as "Lamarcian" is that mutations be not only
directed but also adaptive, i. e. mutations MUST ocuur which obligatorily
lead to improved antigen-antibody binding.<<<<<<<<<<<<<<<<<<<

Mutations in hypervariable regions are hardly "directed" - at least I see
no reasonable mechanism. However there is another aspect which is
implicit in my colleague's posting and which makes the problem
evolutionarily interesting. What the antigen does is selection of an
extremely small part of the genome which then undergoes hypervariation.
But this presupposes specific interaction between the external factor
and "its own" gene. What if environmental evolutionary factors recognize
and select, in the same way, "suitable" parts of the genome? Or, put
differently, parts of the genome "find" "suitable" external factors
and interact with them? There is too much teleological language in this
but still I believe that the immunoglobulin model makes the problem real.

Best regards,
Pentcho Valev




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