32 research outputs found
Detection and classification of positive selection in human populations
No full textDetecting positive selection in genomic regions is a recurrent topic in human population genetics studies. Over the years, many positive selection tests have been implemented to highlight specific genomic patterns left by a selective event when compared to neutral expectations. However, there is little consistency among the regions detected in several genome-wide scans using different tests and/or populations: population-specific demographic dynamics, local genomic features or different types of selection acting along the genome at different times and selective coefficients might explain such discrepancies. The present doctoral thesis is focused in the study of this problem and the development of a innovative solution: a machine-learning classification framework that exploits the combined ability of some selection tests to uncover the different features expected under the hard sweep model, such as sweep completeness and age of onset. The method was calibrated and applied to three reference populations from The 1000 Genome Project to generate a genome-wide classification map of hard selective sweeps. This study improves the way a selective sweep is detected by overcoming the classical selection vs. no-selection classification strategy, and offers an explanation to the lack of consistency observed among selection tests when applied to real data.La detecció de selecció positiva en regions genòmiques ha estat un tema recurrent en molts estudis de genètica de poblacions humanes. En conseqüència, durant els últims anys s'han publicat molts mètodes estadístics per detectar els senyals genòmics creats per un procés de selecció molecular. No obstant això, en general hi ha poca consistència entre les regions detectades pels diferents mètodes: dinàmiques demogràfiques especifiques de població, propietats locals de les regions analitzades o diferents tipus de selecció actuant a diferents marcs temporals i intensitats podrien explicar aquestes discrepàncies. Aquesta tesi doctoral està centrada en l'estudi d'aquest problema i en el desenvolupament d'una solució: un mètode de classificació de selecció positiva basat en algoritmes d'aprenentatge automàtic. El mètode combina diferents tests per detectar selecció positiva per obtenir informació sobre el tipus i mode de selecció que afecta una regió genòmica determinada. Aquest nou mètode presenta una alta sensitivitat cap a senyals de selecció positiva i és capaç de proveir informació sobre l'edat del esdeveniment selectiu, així com del seu estat final. Aquest treball millora la forma en què la selecció positiva és detectada avui en dia i proporciona una explicació a la falta de consistència observada entre els mètodes de detecció de selecció positiva quan s'apliquen en dades reals.Programa de doctorat en Biomedicin
Detection and classification of positive selection in human populations
No full textDetecting positive selection in genomic regions is a recurrent topic in human population genetics studies. Over the years, many positive selection tests have been implemented to highlight specific genomic patterns left by a selective event when compared to neutral expectations. However, there is little consistency among the regions detected in several genome-wide scans using different tests and/or populations: population-specific demographic dynamics, local genomic features or different types of selection acting along the genome at different times and selective coefficients might explain such discrepancies. The present doctoral thesis is focused in the study of this problem and the development of a innovative solution: a machine-learning classification framework that exploits the combined ability of some selection tests to uncover the different features expected under the hard sweep model, such as sweep completeness and age of onset. The method was calibrated and applied to three reference populations from The 1000 Genome Project to generate a genome-wide classification map of hard selective sweeps. This study improves the way a selective sweep is detected by overcoming the classical selection vs. no-selection classification strategy, and offers an explanation to the lack of consistency observed among selection tests when applied to real data.La detecció de selecció positiva en regions genòmiques ha estat un tema recurrent en molts estudis de genètica de poblacions humanes. En conseqüència, durant els últims anys s'han publicat molts mètodes estadístics per detectar els senyals genòmics creats per un procés de selecció molecular. No obstant això, en general hi ha poca consistència entre les regions detectades pels diferents mètodes: dinàmiques demogràfiques especifiques de població, propietats locals de les regions analitzades o diferents tipus de selecció actuant a diferents marcs temporals i intensitats podrien explicar aquestes discrepàncies. Aquesta tesi doctoral està centrada en l'estudi d'aquest problema i en el desenvolupament d'una solució: un mètode de classificació de selecció positiva basat en algoritmes d'aprenentatge automàtic. El mètode combina diferents tests per detectar selecció positiva per obtenir informació sobre el tipus i mode de selecció que afecta una regió genòmica determinada. Aquest nou mètode presenta una alta sensitivitat cap a senyals de selecció positiva i és capaç de proveir informació sobre l'edat del esdeveniment selectiu, així com del seu estat final. Aquest treball millora la forma en què la selecció positiva és detectada avui en dia i proporciona una explicació a la falta de consistència observada entre els mètodes de detecció de selecció positiva quan s'apliquen en dades reals.Programa de doctorat en Biomedicin
How much relevant are male factors for fertilization and early embryo development? Looking into the (epi)genome, proteome and metabolome
No full textInfertility affects 10-15% of couples at the age of conception. Mounting evidence supports that not only are paternal factors crucial during fertilization, but also for embryogenesis. This review aims to provide some clues about the contribution of male factors to reproductive success and live birth, as such contributions can be as important as that of the female. Semen is composed of two fractions: sperm and seminal plasma. Regarding the former, the integrity of sperm components (i.e., centrioles, DNA integrity and methylation, histone-to-protamine ration, specific proteins, etc.) has been proven to be essential for some of the events occurring upon engulfment of the spermatozoon into the oocyte cytoplasm. The metabolic status of sperm also seems to shape their potential fertilizing capacity. Furthermore, seminal plasma appears to modulate the female reproductive tract, and has been suggested to support embryo implantation. In spite of the aforementioned, it remains largely unaddressed how paternal factors interact with maternal ones, and whether the latter may mask the former. While assisted reproductive techniques (ART) are useful to rescue infertility, a better understanding about the contribution of semen to fertilization, embryo development and implantation can increase the efficiency of these techniques, and address further the causes of total fertilization failure, implantation deficiency and recurrent miscarriageThe author also acknowledges the support from the Regional Government of Catalonia, Spain (2017-SGR-1229) and the Catalan Institution for Research and Advanced Studies (ICREA)Open Access funding provided thanks to the CSUC agreement with Cambridge University Press (CUP
Entre l'excepcionalitat i la informalitat : apunts per a un urbanisme postbombolla
No full textSegons els autors l'esclat de la bombolla immobiliària ha tallat en sec la lògica de la plusvàlua que ha governat l'urbanisme fins ara. Aquest fet ha produït dos tipus de respostes que no solucionen pas els problemes derivats de la crisi: la resposta institucional basada en la promoció de megaprojectes (Eurovegas, BCNWorld, etc.), i l'urbanisme autogestionat (pràctiques urbanístiques de microtransformacions, de recuperació temporal d'espais, etc.). Les solucions que plantegen els autors passen per considerar l'urbanisme com a instrument polític, com a eina per al canvi social. Un urbanisme que ha de ser multidisciplinar i col·laboratiu i que gestioni (indivisiblement) tant l'urbanització i l'edificació del sòl, com els canvis del seu valor que la planificació genera
Recent positive selection has acted on genes encoding proteins with more interactions within the whole human interactome
No full textGenes vary in their likelihood to undergo adaptive evolution. The genomic factors that determine adaptability, however, remain poorly understood. Genes function in the context of molecular networks, with some occupying more important positions than others and thus being likely to be under stronger selective pressures. However, how positive selection distributes across the different parts of molecular networks is still not fully understood. Here, we inferred positive selection using comparative genomics and population genetics approaches through the comparison of 10 mammalian and 270 human genomes, respectively. In agreement with previous results, we found that genes with lower network centralities are more likely to evolve under positive selection (as inferred from divergence data). Surprisingly, polymorphism data yield results in the opposite direction than divergence data: Genes with higher centralities are more likely to have been targeted by recent positive selection during recent human evolution. Our results indicate that the relationship between centrality and the impact of adaptive evolution highly depends on the mode of positive selection and/or the evolutionary time-scale.This work was funded by the “Ministerio de Ciencia y Tecnología” (Spain) (grant BFU2013-43726-P), and the “Direcció General de Recerca, Generalitat de Catalunya (Grup de Recerca Consolidat 2009 SGR 1101)” awarded to J.B. P.L. was supported by a Ph.D. fellowship from “Acción Estratégica de Salud, en el marco del Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008–2011” from Instituto de Salud Carlos III. D.A.-P. was a “Juan de la Cierva” fellow from the “Ministerio de Economía y Competitividad” (Spain) (JCI-2011-11089). M.A.F. was supported by a Principal Investigator grant from Science Foundation Ireland (12/IP/1673) and a project from the “Ministerio de Economía y Competitividad” (grant number BFU2012-36346)
Recent positive selection has acted on genes encoding proteins with more interactions within the whole human interactome
No full textGenes vary in their likelihood to undergo adaptive evolution. The genomic factors that determine adaptability, however, remain poorly understood. Genes function in the context of molecular networks, with some occupying more important positions than others and thus being likely to be under stronger selective pressures. However, how positive selection distributes across the different parts of molecular networks is still not fully understood. Here, we inferred positive selection using comparative genomics and population genetics approaches through the comparison of 10 mammalian and 270 human genomes, respectively. In agreement with previous results, we found that genes with lower network centralities are more likely to evolve under positive selection (as inferred from divergence data). Surprisingly, polymorphism data yield results in the opposite direction than divergence data: Genes with higher centralities are more likely to have been targeted by recent positive selection during recent human evolution. Our results indicate that the relationship between centrality and the impact of adaptive evolution highly depends on the mode of positive selection and/or the evolutionary time-scale.This work was funded by the “Ministerio de Ciencia y Tecnología” (Spain) (grant BFU2013-43726-P), and the “Direcció General de Recerca, Generalitat de Catalunya (Grup de Recerca Consolidat 2009 SGR 1101)” awarded to J.B. P.L. was supported by a Ph.D. fellowship from “Acción Estratégica de Salud, en el marco del Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008–2011” from Instituto de Salud Carlos III. D.A.-P. was a “Juan de la Cierva” fellow from the “Ministerio de Economía y Competitividad” (Spain) (JCI-2011-11089). M.A.F. was supported by a Principal Investigator grant from Science Foundation Ireland (12/IP/1673) and a project from the “Ministerio de Economía y Competitividad” (grant number BFU2012-36346)
Recent Positive Selection Has Acted on Genes Encoding Proteins with More Interactions within the Whole Human Interactome
No full textGenes vary in their likelihood to undergo adaptive evolution. The genomic factors that determine adaptability, however, remain poorly understood. Genes function in the context of molecular networks, with some occupying more important positions than others and thus being likely to be under stronger selective pressures. However, how positive selection distributes across the different parts of molecular networks is still not fully understood. Here, we inferred positive selection using comparative genomics and population genetics approaches through the comparison of 10 mammalian and 270 human genomes, respectively. In agreement with previous results, we found that genes with lower network centralities are more likely to evolve under positive selection (as inferred from divergence data). Surprisingly, polymorphism data yield results in the opposite direction than divergence data: Genes with higher centralities are more likely to have been targeted by recent positive selection during recent human evolution. Our results indicate that the relationship between centrality and the impact of adaptive evolution highly depends on the mode of positive selection and/or the evolutionary time-scale.This work was funded by the “Ministerio de Ciencia y Tecnología” (Spain) (grant BFU2013-43726-P), and the “Direcció General de Recerca, Generalitat de Catalunya (Grup de Recerca Consolidat 2009 SGR 1101)” awarded to J.B. P.L. was supported by a Ph.D. fellowship from “Acción Estratégica de Salud, en el marco del Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008–2011” from Instituto de Salud Carlos III. D.A.-P. was a “Juan de la Cierva” fellow from the “Ministerio de Economía y Competitividad” (Spain) (JCI-2011-11089). M.A.F. was supported by a Principal Investigator grant from Science Foundation Ireland (12/IP/1673) and a project from the “Ministerio de Economía y Competitividad” (grant number BFU2012-36346).Peer reviewe
Effect of collapsed duplications on diversity estimates: what to expect
No full textThe study of segmental duplications (SDs) and copy-number variants (CNVs) is of great importance in the fields of genomics and evolution. However, SDs and CNVs are usually excluded from genome-wide scans for natural selection. Because of high identity between copies, SDs and CNVs that are not included in reference genomes are prone to be collapsed-that is, mistakenly aligned to the same region-when aligning sequence data from single individuals to the reference. Such collapsed duplications are additionally challenging because concerted evolution between duplications alters their site frequency spectrum and linkage disequilibrium patterns. To investigate the potential effect of collapsed duplications upon natural selection scans we obtained expectations for four summary statistics from simulations of duplications evolving under a range of interlocus gene conversion and crossover rates. We confirm that summary statistics traditionally used to detect the action of natural selection on DNA sequences cannot be applied to SDs and CNVs since in some cases values for known duplications mimic selective signatures. As a proof of concept of the pervasiveness of collapsed duplications, we analyzed data from the 1,000 Genomes Project. We find that, within regions identified as variable in copy number, diversity between individuals with the duplication is consistently higher than between individuals without the duplication. Furthermore, the frequency of single nucleotide variants (SNVs) deviating from Hardy-Weinberg Equilibrium is higher in individuals with the duplication, which strongly suggests that higher diversity is a consequence of collapsed duplications and incorrect evaluation of SNVs within these CNV regions.This work has been supported by Ministerio de Ciencia e Innovación, Spain (BFU2015-68649-P, MINECO/FEDER, UE), the Direcció General de Recerca, Generalitat de Catalunya (2014SGR1311 and 2014SGR866), the Spanish National Institute of Bioinformatics (PT13/0001/0026) of the Instituto de Salud Carlos III, grant MDM-2014-0370 through the “María de Maeztu” Programme for Units of Excellence in R&D to UPF’s Department of Experimental and Health Sciences; a grant to D.A.H. from Conacyt; and by the Fondo Europeo de Desarrollo Regional (FEDER) and the Fondo Social Europeo (FSE)
1000 Genomes Selection Browser 1.0: A genome browser dedicated to signatures of natural selection in modern humans
No full textThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Searching for Darwinian selection in natural populations has been the focus of a multitude of studies over the last decades. Here we present the 1000 Genomes Selection Browser 1.0 (http://hsb.upf.edu) as a resource for signatures of recent natural selection in modern humans. We have implemented and applied a large number of neutrality tests as well as summary statistics informative for the action of selection such as Tajima's D, CLR, Fay and Wu's H, Fu and Li's F* and D*, XPEHH, ΔiHH, iHS, FST, ΔDAF and XPCLR among others to low coverage sequencing data from the 1000 genomes project (Phase 1; release April 2012). We have implemented a publicly available genome-wide browser to communicate the results from three different populations of West African, Northern European and East Asian ancestry (YRI, CEU, CHB). Information is provided in UCSC-style format to facilitate the integration with the rich UCSC browser tracks and an access page is provided with instructions and for convenient visualization. We believe that this expandable resource will facilitate the interpretation of signals of selection on different temporal, geographical and genomic scales. © 2013 The Author(s). Published by Oxford University Press.Ministerio de Ciencia y Tecnología (Spain); Direcció General de Recerca, Generalitat de Catalunya (Grup de Recerca Consolidat 2009 SGR 1101); Subprogram BMC [BFU2010-19443 awarded to J.B.]; Post-doctoral scholarship from the Volkswagenstiftung [Az: I/85 198 to J.E.]; Spanish government [BFU-2008-01046; SAF2011-29239]; The Spanish government FPI scholarships [BES-2009-017731 and BES-2011-04502 to G.M.D. and M.P., respectively]; PhD fellowship from ‘Acción Estratégica de Salud, en el marco del Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008-2011’ from Instituto de Salud Carlos III (to P.L.). Funding for open access charge: Prof. Jaume Bertranpetit.Peer Reviewe
Chromatin condensation but not DNA integrity of pig sperm is greater in the sperm-rich fraction
No full text©The Author(s) 2023. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in Journal of Animal Science and Biotechnology. To access the final edited and published work see https://doi.org/
https://doi.org/10.1186/s40104-023-00938-wBackground protamination and condensation of sperm chromatin as well as DNA integrity play an essential role during fertilization and embryo development. In some mammals, like pigs, ejaculates are emitted in three separate fractions: pre-sperm, sperm-rich (SRF) and post sperm-rich (PSRF). These fractions are known to vary in volume, sperm concentration and quality, as well as in the origin and composition of seminal plasma (SP), with differences being also observed within the SRF one. Yet, whether disparities in the DNA integrity and chromatin condensation and protamination of their sperm exist has not been interrogated. Results This study determined chromatin protamination (Chromomycin A3 test, CMA3), condensation (Dibromobi‑mane test, DBB), and DNA integrity (Comet assay) in the pig sperm contained in the frst 10 mL of the SRF (SRF-P1),
the remaining portion of the sperm-rich fraction (SRF-P2), and the post sperm-rich fraction (PSRF). While chromatin protamination was found to be similar between the diferent ejaculate fractions (P>0.05), chromatin condensation was seen to be greater in SRF-P1 and SRF-P2 than in the PSRF (P=0.018 and P=0.004, respectively). Regarding DNA integrity, no diferences between fractions were observed (P>0.05). As the SRF-P1 has the highest sperm concentra‑tion and ejaculate fractions are known to difer in antioxidant composition, the oxidative stress index (OSi) in SP, calcu‑
lated as total oxidant activity divided by total antioxidant capacity, was tested and confrmed to be higher in the SRFP1 than in SRF-P2 and PSRF (0.42±0.06 vs. 0.23±0.09 and 0.08±0.00, respectively; P<0.01); this index, in addition, was observed to be correlated to the sperm concentration of each fraction (Rs=0.973; P<0.001). Conclusion While sperm DNA integrity was not found to difer between ejaculate fractions, SRF-P1 and SRF-P2 were observed to exhibit greater chromatin condensation than the PSRF. This could be related to the OSi of each fraction
