Information Technology Reference
In-Depth Information
nism could have co-evolved with mutational mechanisms in virus and bacteria fo-
cusing in each case in recognition molecules (
e.g.,
Ig V regions in the first case and
invasiveness molecules, like influenza hemaglutinin, in the second case), leading af-
ter a race similar high mutation rates and similar diversity generation compatible
with the physiology of those molecules.
Many related important questions remain to be explored. What determines
the SHM rate? Is it optimal? What determines the time of duration of the GCR?
Under the view suggested above this time would be related not only to the mu-
tation rate, but also to the diversity generated. For a given mutation rate, the
diversity generated and the probability to spoil the physiologyof the Abs will
increase with the duration of the GC reaction. Thus, the mutation rate and the
duration of the mutational process will be the maximum compatible with pre-
serving the role of the Abs, while the mutational mechanism of microorganisms
must be limited also in their rates and the length of the period time in which it
is active, being at rest in non-stressing environments.
Acknowledgments
The authors thank Jorge Carneiro and Joana Moreira for constructive comments
on this work. This work was supported by Fundacao para Ciencia e Tecnologia,
Portugal (grant to JF, POCTI/36413/1999, SFRH/BPD/8104/2002 to IG and
SFRH/BD/5235/2001 to JC). JF is supported by an Isidro Parga Pondal re-
search contract by Xunta de Galicia, Spain.
References
1. Janeway, C., Travers, P., Walport, M., Shlomchik, M.: Immunobiology: the immune
system in health and disease. 6th edn. Garland Science, New York (2004)
2. Flajnik, M.F.: Comparative analyses of immunoglobulin genes: surprises and por-
tents. Nat Rev Immunol.
2
(2002) 688-698.
3. MacLennan, I. C.: Germinal centers. Annu. Rev. Immunol.
12
(1994) 117-139.
4. Kelsoe, G.: In situ studies of the germinal center reaction. Adv Immunol.
60
(1995)
267-288.
5. Fagarasan, S., Muramatsu, M., Suzuki, K., Nagaoka, H., Hiai, H. and Honjo, T.:
Critical roles of activation-induced cytidine deaminase in the homeostasis of gut
flora. Science
298
(2002) 1424-1427.
6. Gordo, I. and Dionisio, F.: Nonequilibrium model for estimating parameters of
deleterious mutations. Phys Rev E Stat Nonlin Soft Matter Phys.
71
(2005) 031907.
7. Gordo, I. and Charlesworth, B.: On the speed of Muller's ratchet. Genetics.
156
(2000) 2137-2140.
8. Bachtrog, D. and Gordo, I.: Adaptive evolution of asexual populations under
Muller's ratchet. Evolution Int J Org Evolution.
58
(2004) 1403-1413.
9. Kimura, M.: The neutral theory of molecular evolution. Cambridge University
Press, Cambridge [Cambridgeshire] New York (1983)
10. Charlesworth, B., Morgan, M. T. and Charlesworth, D.: The effect of deleterious
mutations on neutral molecular variation. Genetics.
134
(1993) 1289-1303.
11. Smith, J. M. and Haigh, J.: The hitch-hiking effect of a favourable gene. Genet
Res
23
(1974) 23-35.
