A variety of enzyme inhibitors have been developed in combating HIV-1, however the fast evolutionary rate of this virus commonly leads to the emergence of resistance mutations that finally allows the mutant virus to survive. This review explores the main genetic consequences of HIV-1 molecular evolution during antiviral therapies, including the viral genetic diversity and molecular adaptation. The role of recombination in the generation of drug resistance is also analyzed. Besides the investigation and discussion of published works, an evolutionary analysis of protease-coding genes collected from patients before and after treatment with different protease inhibitors was included to validate previous studies. Finally, the review discusses the importance of considering genetic consequences of antiviral therapies in models of HIV-1 evolution that could improve current genotypic resistance testing and treatments design. ; Thiswork was supported by the Spanish Government through the "Juan de la Cierva" Fellowship JCI-2011-10452 and by the Portuguese Government through the FCT Starting Grant IF/00955/2014. ; Peer Reviewed
Knowledge of orchid diversity has greatly expanded in the last 30 years. Some 1,150 identified species are recognized in Mexico with an additional 100 species still unidentified. Some 250 localities have been surveyed with "hot spots" of orchid diversity identified. Cloud forests contain almost 60% of known species in only 2% of territory; this is the most endangered biome. A map of priority regions for conservation is available. A federal list of endangered or threatened species has been published. Official development policies have changed from massive clearing to biodiversity conservation. Demographic and genetic surveys have taken place in particularly threatened and economically important species like Laelia speciosa and Vanilla. Cases of conflicting interests in horticulture oppose orchid growers with in situ conservation. Ex situ conservation of Laelia anceps subsp. dawsonii, L. gouldiana, Paphiopedilum xerophyticum and P. exstaminodium results in commercial gain. A National Plan for Orchid Conservation focusing on immediate actions is underway. Various projects of in situ conservation are ongoing with legal support. A realistic assessment of commercial possibilities of local species is essential to avoid exaggerated expectations. Interaction of local groups, government and NGO's with local communities is essential to biodiversity conservation.
Despite intense work, incorporating constraints on protein native structures into the mathematical models of molecular evolution remains difficult, because most models and programs assume that protein sites evolve independently, whereas protein stability is maintained by interactions between sites. Here, we address this problem by developing a new meanfield substitution model that generates independent site-specific amino acid distributions with constraints on the stability of the native state against both unfolding and misfolding. The model depends on a background distribution of amino acids and one selection parameter that we fix maximizing the likelihood of the observed protein sequence. The analytic solution of the model shows that the main determinant of the site-specific distributions is the number of native contacts of the site and that themost variable sites are those with an intermediate number of native contacts. The meanfield models obtained, taking into account misfolded conformations, yield larger likelihood than models that only consider the native state, because their average hydrophobicity is more realistic, and they produce on the average stable sequences for most proteins. We evaluated the mean-field model with respect to empirical substitution models on 12 test data sets of different protein families. In all cases, the observed site-specific sequence profiles presented smaller Kullback–Leibler divergence from the mean-field distributions than from the empirical substitution model. Next, we obtained substitution rates combining the mean-field frequencies with an empirical substitution model. The resulting mean-field substitutionmodel assigns larger likelihood than the empiricalmodel to all studied families when we consider sequences with identity larger than 0.35, plausibly a condition that enforces conservation of the native structure across the family. We found that the mean-field model performs better than other structurally constrained models with similar or higher complexity. With respect to the much more complex model recently developed by Bordner and Mittelmann, which takes into account pairwise terms in the amino acid distributions and also optimizes the exchangeability matrix, our model performed worse for data with small sequence divergence but better for data with larger sequence divergence. The mean-field model has been implemented into the computer program Prot_Evol that is freely available at ttp://ub.cbm.uam.es/software/Prot_Evol.php ; Ministery of Economy through the grant BFU-40020 to U.B. M.A. was supported by the Spanish Government through the Juan de la Cierva fellowship JCI-2011-10452. Research at the CBMSO is facilitated by the Fundación Ramón Areces ; Peer Reviewed
The estimation of substitution and recombination rates can provide important insights into the molecular evolution of protein-coding sequences. Here, we present a new computational framework, called "CodABC," to jointly estimate recombination, substitution and synonymous and nonsynonymous rates from coding data. CodABC uses approximate Bayesian computation with and without regression adjustment and implements a variety of codon models, intracodon recombination, and longitudinal sampling. CodABC can provide accurate joint parameter estimates from recombining coding sequences, often outperforming maximum-likelihood methods based on more approximate models. In addition, CodABC allows for the inclusion of several nuisance parameters such as those representing codon frequencies, transition matrices, heterogeneity across sites or invariable sites. CodABC is freely available from http://code.google.com/p/codabc/, includes a GUI, extensive documentation and ready-to-use examples, and can run in parallel on multicore machines. ; This work was supported by the Spanish Government with the "Juan de la Cierva" fellowship JCI-2011-10452 to M.A., the European Research Council (ERC Grant Agreement No. 617457) to D.P., and Fundac¸~ao para a Ci^encia e a Tecnologia (FCT) (grant EXCL/BIA-ANM/0549/2012) to J.S.L. ; Peer reviewed
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 toward 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 modeled upon a previous Neolithic expansion, it effectively favored 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 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 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 further evolutionary scenarios could be evaluated to obtain an accurate understanding of the causes of the Iberian genetic gradient, here we suggest that this gradient has a more complex explanation than that previously hypothesized. ; The simulated data and corresponding PC maps associated to this study are here deposited. See README.txt for details about the provided data.
The Iberian Peninsula is a well-delimited geographic region with a rich and complex human history. However, the causes of its genetic structure and past migratory dynamics are not yet fully understood. In order to shed light on them, here we evaluated the gene flow and genetic structure throughout the Iberian Peninsula with spatially explicit modelling applied to a georeferenced genetic dataset composed of genome-wide SNPs from 746 individuals belonging to 17 different regions of the Peninsula. We found contrasting patterns of genetic structure throughout Iberia. In particular, we identified strong patterns of genetic differentiation caused by relevant barriers to gene flow in northern regions and, on the other hand, a large genetic similarity in central and southern regions. In addition, our results showed a preferential north to south migratory dynamics and suggest a sex-biased dispersal in Mediterranean and southern regions. The estimated genetic patterns did not fit with the geographical relief of the Iberian landscape and they rather seem to follow political and linguistic territorial boundaries.
The Iberian Peninsula is a well-delimited geographic region with a rich and complex human history. However, the causes of its genetic structure and past migratory dynamics are not yet fully understood. In order to shed light on them, here we evaluated the gene flow and genetic structure throughout the Iberian Peninsula with spatially explicit modelling applied to a georeferenced genetic dataset composed of genome-wide SNPs from 746 individuals belonging to 17 different regions of the Peninsula. We found contrasting patterns of genetic structure throughout Iberia. In particular, we identified strong patterns of genetic differentiation caused by relevant barriers to gene flow in northern regions and, on the other hand, a large genetic similarity in central and southern regions. In addition, our results showed a preferential north to south migratory dynamics and suggest a sex-biased dispersal in Mediterranean and southern regions. The estimated genetic patterns did not fit with the geographical relief of the Iberian landscape and they rather seem to follow political and linguistic territorial boundaries. ; IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). J.P. and A.M.L. are funded by the Portuguese Government through the FCT fellowship SFRH/BD/97200/2013 and the research contract IF/01262/2014, respectively. M.A. was supported by the "Ramón y Cajal" grant RYC-2015-18241 from the Spanish Government. D.C. was supported by the Spanish grant CGL2016-75389-P (AEI, MINEICO/FEDER, UE), and "Unidad María de Maeztu" funded by the MINECO (MDM-2014-0370).
The Iberian Peninsula is a well-delimited geographic region with a rich and complex human history. However, the causes of its genetic structure and past migratory dynamics are not yet fully understood. In order to shed light on them, here we evaluated the gene flow and genetic structure throughout the Iberian Peninsula with spatially explicit modelling applied to a georeferenced genetic dataset composed of genome-wide SNPs from 746 individuals belonging to 17 different regions of the Peninsula. We found contrasting patterns of genetic structure throughout Iberia. In particular, we identified strong patterns of genetic differentiation caused by relevant barriers to gene flow in northern regions and, on the other hand, a large genetic similarity in central and southern regions. In addition, our results showed a preferential north to south migratory dynamics and suggest a sex-biased dispersal in Mediterranean and southern regions. The estimated genetic patterns did not fit with the geographical relief of the Iberian landscape and they rather seem to follow political and linguistic territorial boundaries. ; IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). J.P. and A.M.L. are funded by the Portuguese Government through the FCT fellowship SFRH/BD/97200/2013 and the research contract IF/01262/2014, respectively. M.A. was supported by the "Ramón y Cajal" grant RYC-2015-18241 from the Spanish Government. D.C. was supported by the Spanish grant CGL2016-75389-P (AEI, MINEICO/FEDER, UE), and "Unidad María de Maeztu" funded by the MINECO (MDM-2014-0370).
The Iberian Peninsula is a well-delimited geographic region with a rich and complex human history. However, the causes of its genetic structure and past migratory dynamics are not yet fully understood. In order to shed light on them, here we evaluated the gene flow and genetic structure throughout the Iberian Peninsula with spatially explicit modelling applied to a georeferenced genetic dataset composed of genome-wide SNPs from 746 individuals belonging to 17 different regions of the Peninsula. We found contrasting patterns of genetic structure throughout Iberia. In particular, we identified strong patterns of genetic differentiation caused by relevant barriers to gene flow in northern regions and, on the other hand, a large genetic similarity in central and southern regions. In addition, our results showed a preferential north to south migratory dynamics and suggest a sex-biased dispersal in Mediterranean and southern regions. The estimated genetic patterns did not fit with the geographical relief of the Iberian landscape and they rather seem to follow political and linguistic territorial boundaries. ; IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). J.P. and A.M.L. are funded by the Portuguese Government through the FCT fellowship SFRH/BD/97200/2013 and the research contract IF/01262/2014, respectively. M.A. was supported by the "Ramón y Cajal" grant RYC-2015-18241 from the Spanish Government. D.C. was supported by the Spanish grant CGL2016-75389-P (AEI, MINEICO/FEDER, UE), and "Unidad María de Maeztu" funded by the MINECO (MDM-2014-0370) ; SI
This study was funded by grant 4278 of the British Ecological Society, grants CGL2011-28177, CGL2014-53899-P, CGL2017-85191-P, and RYC-2015-18241 from the Spanish Ministry of Science, grant LIQUENES 2014 (CN-13-058) from FICYT and edp-HC Energía, and a GRUPIN research grant from the Regional Government of Asturias (Ref.: IDI/2018/000151).
