Epistasis as a Determinant of the HIV-1 Protease's Robustness to Mutation
Capel Malo, Elena (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Parera, Mariona (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martinez, Miguel Angel (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)

Date:	2014
Abstract:	The robustness of phenotypes to mutation is critical to protein evolution; robustness may be an adaptive trait if it promotes evolution. We hypothesised that native proteins subjected to natural selection in vivo should be more robust than proteins generated in vitro in the absence of natural selection. We compared the mutational robustness of two human immunodeficiency virus type 1 (HIV-1) proteases with comparable catalytic efficiencies, one isolated from an infected individual and the second generated in vitro via random mutagenesis. Single mutations in the protease (82 and 60 in the wild-type and mutant backgrounds, respectively) were randomly generated in vitro and the catalytic efficiency of each mutant was determined. No differences were observed between these two protease variants when lethal, neutral, and deleterious mutations were compared (P = 0. 8025, chi-squared test). Similarly, average catalytic efficiency (-72. 6% and -64. 5%, respectively) did not significantly differ between protease mutant libraries (P = 0. 3414, Mann Whitney test). Overall, the two parental proteins displayed similar mutational robustness. Importantly, strong and widespread epistatic interactions were observed when the effect of the same mutation was compared in both proteases, suggesting that epistasis can be a key determinant of the robustness displayed by the in vitro generated protease.
Grants:	Ministerio de Economía y Competitividad SAF2013-41421-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 9 (december 2014) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0116301
PMID: 25551558

14 p, 494.6 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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