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Antibodies used to understand Evolution and Natural Selection.

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Understanding and describing the outcome of selection in population of mutants in a given selective pressure is essential from many points of view. Actually it opens perspectives in field ranging from understanding immune system response to rationalisation of protein library (population of mutants) design in the pharmaceutical industry.

By using a model system, a subpart of antibodies involved in binding antigens, and a controlled in vitro selection technique associated with the high throughput sequencing technology, we showed the importance of library design in terms of its intensity of response to selection. This experimental set up based on the binding between antibodies and a controlled chosen target is comparing for the first time the outcome of selection for antibodies libraries that differ by their scaffold or evolutionary history but which share the same distribution of binding pocket. We showed that describing result of selection using extreme value statistic was plausible and informative. In this context, two parameters are needed to describe the outcome of selection. One in particular, the shape parameter \kappa defines the spacing between mutant in term of selectivity (a proxy for the variable under selection). It also sets the scale of mutant improvement if the diversity of the library is increased.

These results have been published in PNAS.