The history of modern humans in the Iberian Peninsula includes a variety of population arrivals sometimes presenting admixture with resident populations. Genetic data from current Iberian populations revealed an overall east - west genetic gradient that some authors interpreted as a direct consequence of the Reconquista, where Catholic Kingdoms expanded their territories towards the south while displacing Muslims. However, this interpretation has not been formally evaluated. Here, we present a qualitative analysis of the causes of the current genetic gradient observed in the Iberian Peninsula using extensive spatially-explicit computer simulations based on a variety of evolutionary scenarios. Our results indicate that the Neolithic range expansion clearly produces the orientation of the observed genetic gradient. Concerning the Reconquista (including political borders among Catholic Kingdoms and regions with different languages), if modelled upon a previous Neolithic expansion it effectively favoured the orientation of the observed genetic gradient and shows local isolation of certain regions (i.e., Basques and Galicia). Despite additional evolutionary scenarios could be evaluated to more accurately decipher the causes of the Iberian genetic gradient, here we show that this gradient has a more complex explanation than that previously hypothesized.

The evolution of structural proteins is generally constrained by the folding stability. However, little is known about the particular capacity of viral proteins to accommodate mutations that can potentially affect the protein stability and, in general, the evolution of the protein stability over time. As an illustrative model case, here we investigated the evolution of the stability of the HIV-1 protease (PR), which is a common HIV-1 drug target, under diverse evolutionary scenarios that include (i) intra-host virus evolution in a cohort of 75 patients sampled over time, (ii) intra-host virus evolution sampled before and after specific PR-based treatments and, (iii) inter-host evolution considering extant and ancestral (reconstructed) PR sequences from diverse HIV-1 subtypes. We also investigated the specific influence of currently known HIV-1 PR resistance mutations on the PR folding stability. We found that the HIV-1 PR stability fluctuated over time within a constant and wide range in any studied evolutionary scenario, accommodating multiple mutations that partially affected stability while maintaining activity. We did not identify relationships between change of PR stability and diverse clinical parameters such as viral load, CD4+ T cell counts and a surrogate of time from infection. Counterintuitively, we predicted that near half of the studied HIV-1 PR resistance mutations do not significantly decrease stability, which together with compensatory mutations, would allow the protein to adapt without requiring dramatic stability changes. We conclude that the HIV-1 PR presents a wide structural plasticity to acquire molecular adaptations without affecting the overall evolution of stability.

No abstract

No abstract