A stochastic model for the rapid emergence of specific vertebrate immunity incorporating horizontal transfer of systems enabling duplication and combinational diversification.
Recent molecular data indicate that the antigen-specific combinatorial immune response is restricted to jawed vertebrates where it is found in representatives of all class from cartilagenous fishes to mammals. Here, we analyse the relatively rapid emergence of the combinatorial system terms of three stochastic process, with the system reaching essentially full capacity in immunoglobulin recognition elements and diversification and recombination of gene segments in an evolutionary span of time of less than 20 million years. The mechanisms for inducibility were coopted from ancient and widely spread processes in phylogeny for regulation of cell division. The proposed process of formation entailed the evolution of unknown ancestral genes into those specifying bona fide immunoglobulin domains, and the generation of multiple copies of these via a series of events facilitated by horizontal transfer of site-specific recombinases and recombination signal sequences most probably from microbial and fungal sources. The second process is one of rapid "decay" (evolution) which occurred in about 10 million year under stringent selective conditions to generate proper conserved canonical sequences. The third process is that of the long term evolution of these characteristic immunoglobulin domains over the 450 million years since their emergence. As a first approximation the rates of these three processes were computed using first order differential equations. The rate of formation has a magnitude of 10-7 substitutions per site per year, and that of rapid modifications is 10-8 substitutions per site per year. The long term rate of immunoglobulin evolution is comparable to that of other moderately conserved proteins, (1-3) x 10-9 substitutions per site per year). This model is testable by searching for "footprints" of microbial and fungal DNA processing enzymes and recombination mechanisms. The hypothesis raises the general concept that horizontal transfer of genes facilitating rearrangement and duplication can catalyse major steps of macroevolution.
Marchalonis
J J
JJ
Department of Microbiology and Immunology, University of Arizona, Tucson 85724-5049, USA.
Schluter
S F
SF
D000818:Animals; D019143:Evolution, Molecular; D007113:Immunity, Innate; D007136:Immunoglobulins / Q000235:genetics*; D018448:Models, Immunological; D014714:Vertebrates / Q000235:genetics / Q000276:immunology*
D007136:Immunoglobulins