Suchergebnisse

DNA methylation is an epigenetic modification involved in regulatory processes such as cell differentiation during development, X-chromosome inactivation, genomic imprinting and susceptibility to complex disease. However, the dynamics of DNA methylation changes between humans and their closest relatives are still poorly understood. We performed a comparative analysis of CpG methylation patterns between 9 humans and 23 primate samples including all species of great apes (chimpanzee, bonobo, gorilla and orangutan) using Illumina Methylation450 bead arrays. Our analysis identified ∼800 genes with significantly altered methylation patterns among the great apes, including ∼170 genes with a methylation pattern unique to human. Some of these are known to be involved in developmental and neurological features, suggesting that epigenetic changes have been frequent during recent human and primate evolution. We identified a significant positive relationship between the rate of coding variation and alterations of methylation at the promoter level, indicative of co-occurrence between evolution of protein sequence and gene regulation. In contrast, and supporting the idea that many phenotypic differences between humans and great apes are not due to amino acid differences, our analysis also identified 184 genes that are perfectly conserved at protein level between human and chimpanzee, yet show significant epigenetic differences between these two species. We conclude that epigenetic alterations are an important force during primate evolution and have been under-explored in evolutionary comparative genomics. © 2013 Hernando-Herraez et al. ; TMB is supported by the European Research Council (ERC Starting Grant, StG_20091118) and the Spanish Government (BFU2011-28549). AJS is supported by NIH grants 1R01DA033660, 1R01HG006696, and a grant from the Alzheimer's Association (2012ALZNIRG69983). IHH is supported by the European Social Fund, AGAUR (Generalitat de Catalunya, Spain) and the Spanish National Research Council (CSIC). We also thank the Spanish Government for the grant BFU2009-13409-C02-02 to AN and the Barcelona Zoo (Ajuntament de Barcelona) for an award to JPM. ; Peer Reviewed

Background] Numerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate. Here, we explore the immediate genetic impact of the Ebola outbreak in the western lowland gorilla population. [Results] Associations with survivorship were evaluated by utilizing DNA obtained from fecal samples from 16 gorilla individuals declared missing after the outbreak (non-survivors) and 15 individuals observed before and after the epidemic (survivors). We used a target enrichment approach to capture the sequences of 123 genes previously associated with immunology and Ebola virus resistance and additionally analyzed the gut microbiome which could influence the survival after an infection. Our results indicate no changes in the population genetic diversity before and after the Ebola outbreak, and no significant differences in microbial community composition between survivors and non-survivors. However, and despite the low power for an association analysis, we do detect six nominally significant missense mutations in four genes that might be candidate variants associated with an increased chance of survival. [Conclusion] This study offers the first insight to the genetics of a wild great ape population before and after an Ebola outbreak using target capture experiments from fecal samples, and presents a list of candidate loci that may have facilitated their survival. ; C.F. is supported by "la Caixa" PhD fellowship, fellowship code LCF/BQ/DE15/10360006. M.K. is supported by "la Caixa" Foundation (ID 100010434), fellowship code LCF/BQ/PR19/11700002. J. N is supported by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 676154 (ArchSci2020) and an EMBO short-term fellowship STF-8036. P.F. is supported by the Innovation Fund Denmark. H.R.S is supported by The Danish Council for Independent Research | Natural Sciences. A.N. is supported by BFU2015–68649-P (MINECO/FEDER, UE). M.T.P.G. is supported by the Danish Basic Research Foundation award DNRF143. T.M.-B is supported by funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 864203), BFU2017–86471-P (MINECO/FEDER, UE), "Unidad de Excelencia María de Maeztu", funded by the AEI (CEX2018-000792-M), Howard Hughes International Early Career and Secretaria d'Universitats i Recerca and CERCA Programme del Departament d'Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). P.L.G., N.M. and D.V. are supported by the French National agency for research via the ANR-11-JVS7–015 IDiPop project. D.H. is supported by Wellcome Investigator Award (202802/Z/16/Z) and works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1–7). This long-term research on gorillas was funded by the ECOsystèmes FORestiers program (Ministère de l'Ecologie et du Développement Durable France), the Espèces-Phares program (DG Environnement, UE) and Lundbeck Foundation Visiting Professorship R317–2019-5 grant to T.M.-B. and M.T.P.G. This work was supported by: AEI-PGC2018–101927-BI00(FEDER/UE).

Background: Numerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate. Here, we explore the immediate genetic impact of the Ebola outbreak in the western lowland gorilla population. Results: Associations with survivorship were evaluated by utilizing DNA obtained from fecal samples from 16 gorilla individuals declared missing after the outbreak (non-survivors) and 15 individuals observed before and after the epidemic (survivors). We used a target enrichment approach to capture the sequences of 123 genes previously associated with immunology and Ebola virus resistance and additionally analyzed the gut microbiome which could influence the survival after an infection. Our results indicate no changes in the population genetic diversity before and after the Ebola outbreak, and no significant differences in microbial community composition between survivors and non-survivors. However, and despite the low power for an association analysis, we do detect six nominally significant missense mutations in four genes that might be candidate variants associated with an increased chance of survival. Conclusion: This study offers the first insight to the genetics of a wild great ape population before and after an Ebola outbreak using target capture experiments from fecal samples, and presents a list of candidate loci that may have facilitated their survival. ; C.F. is supported by "la Caixa" PhD fellowship, fellowship code LCF/BQ/DE15/10360006. M.K. is supported by "la Caixa" Foundation (ID 100010434), fellowship code LCF/BQ/PR19/11700002. J. N is supported by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 676154 (ArchSci2020) and an EMBO short-term fellowship STF-8036. P.F. is supported by the Innovation Fund Denmark. H.R.S is supported by The Danish Council for Independent Research | Natural Sciences. A.N. is supported by BFU2015–68649-P (MINECO/FEDER, UE). M.T.P.G. is supported by the Danish Basic Research Foundation award DNRF143. T.M.-B is supported by funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 864203), BFU2017–86471-P (MINECO/FEDER, UE), "Unidad de Excelencia María de Maeztu", funded by the AEI (CEX2018-000792-M), Howard Hughes International Early Career and Secretaria d'Universitats i Recerca and CERCA Programme del Departament d'Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). P.L.G., N.M. and D.V. are supported by the French National agency for research via the ANR-11-JVS7–015 IDiPop project. D.H. is supported by Wellcome Investigator Award (202802/Z/16/Z) and works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1–7). This long-term research on gorillas was funded by the ECOsystèmes FORestiers program (Ministère de l'Ecologie et du Développement Durable France), the Espèces-Phares program (DG Environnement, UE) and Lundbeck Foundation Visiting Professorship R317–2019-5 grant to T.M.-B. and M.T.P.G. This work was supported by: AEI-PGC2018–101927-BI00(FEDER/UE).