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Genetics, Vol. 178, 1533-1545, March 2008, Copyright © 2008
doi:10.1534/genetics.107.082792

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Lgals6, a 2-Million-Year-Old Gene in Mice: A Case of Positive Darwinian Selection and Presence/Absence Polymorphism

Denis Houzelstein*,1,2, Isabelle R. Gonçalves*,{dagger},1, Annie Orth{ddagger}, François Bonhomme{ddagger} and Pierre Netter*

* Institut Jacques Monod, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7592, Université Pierre et Marie Curie, Paris 06, Université Denis Diderot, Paris 07, 75251 Paris, France, {dagger} Atelier de Bioinformatique, Université Pierre et Marie Curie, Paris 06, 75005 Paris, France and {ddagger} Biologie Intégrative, ISE-M, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5554, Université Montpellier 2, 34095 Montpellier, France

2 Corresponding author: Laboratoire Structure et Dynamique des Génomes, Institut Jacques Monod, 2, place Jussieu, 75251 Paris Cedex 05, France.
E-mail: houzelstein{at}ijm.jussieu.fr

Duplications of genes are widely considered to be a driving force in the evolutionary process. The fate of such duplicated genes (paralogs) depends mainly on the early stages of their evolution. Therefore, the study of duplications that have already started to diverge is useful to better understand their evolution. We present here the example of a 2-million-year-old segmental duplication at the origin of the Lgals4 and Lgals6 genes in the mouse genome. We analyzed the distribution of these genes in samples from 110 wild individuals and wild-derived inbred strains belonging to eight mouse species from Mus (Coelomys) pahari to M. musculus and 28 laboratory strains. Using a maximum-likelihood method, we show that the sequence of the Lgals6 gene has evolved under the influence of strong positive selection that is likely to result in its neofunctionalization. Surprisingly, despite this selection pressure, the Lgals6 gene is present in some mouse species, but not all. Furthermore, even within the species and populations where it is present, the Lgals6 gene is never fixed. To explain this paradox, we propose different hypotheses such as balanced selection and neutral retention of ancient polymophism and we discuss this unexpected result with regard to known galectin properties and response to infections by pathogens.






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