Modern human contamination is a common problem in ancient DNA studies. We provide evidence that this issue is also present in studies in great apes, which are our closest living relatives, for example in noninvasive samples. Here, we present a simple method to detect human contamination in short-read sequencing data from different species: HuConTest. We demonstrate its feasibility using blood and tissue samples from these species. This test is particularly useful for more complex samples (such as museum and noninvasive samples) which have smaller amounts of endogenous DNA, as we show here. ; M.K. is supported by "la Caixa" Foundation (ID 100010434), fellowship code LCF/BQ/PR19/11700002. M.A.E. is supported by an FPI (Formación de Personal Investigador) PRE2018-083966 from Ministerio de Ciencia, Universidades e Investigación. 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, Obra Social "La Caixa" and Secretaria d'Universitats i Recerca and CERCA Programme del Departament d'Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). ; With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2018-000792-M). ; Peer reviewed
The phylogenetic relationships between hominins of the Early Pleistocene epoch in Eurasia, such as Homo antecessor, and hominins that appear later in the fossil record during the Middle Pleistocene epoch, such as Homo sapiens, are highly debated1-5. For the oldest remains, the molecular study of these relationships is hindered by the degradation of ancient DNA. However, recent research has demonstrated that the analysis of ancient proteins can address this challenge6-8. Here we present the dental enamel proteomes of H. antecessor from Atapuerca (Spain)9,10 and Homo erectus from Dmanisi (Georgia)1, two key fossil assemblages that have a central role in models of Pleistocene hominin morphology, dispersal and divergence. We provide evidence that H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans. This placement implies that the modern-like face of H. antecessor-that is, similar to that of modern humans-may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form. By recovering AMELY-specific peptide sequences, we also conclude that the H. antecessor molar fragment from Atapuerca that we analysed belonged to a male individual. Finally, these H. antecessor and H. erectus fossils preserve evidence of enamel proteome phosphorylation and proteolytic digestion that occurred in vivo during tooth formation. Our results provide important insights into the evolutionary relationships between H. antecessor and other hominin groups, and pave the way for future studies using enamel proteomes to investigate hominin biology across the existence of the genus Homo. ; F.W. is supported by a Marie Skłodowska Curie Individual Fellowship (no. 795569). E. Cappellini was supported by VILLUM FONDEN (no. 17649). E.W. is supported by the Lundbeck Foundation, the Danish National Research Foundation, the Novo Nordisk Foundation, the Carlsberg Foundation, KU2016 and the Wellcome Trust. Without the effort of the members of the Atapuerca research team during fieldwork, this work would have not been possible; we make a special mention of J. Rosell, who supervises the excavation of the TD6 level. The research of the Atapuerca project has been supported by the Dirección General de Investigación of the Ministerio de Ciencia, Innovación y Universidades (grant numbers PGC2018-093925-B-C31, C32, and C33); field seasons are supported by the Consejería de Cultura y Turismo of the Junta de Castilla y León and the Fundación Atapuerca. We acknowledge The Leakey Foundation through the personal support of G. Getty (2013) and D. Crook (2014–2016, 2018, and 2019) to M.M.-T., as well as F.W. (2017). Restoration and conservation work on the material have been carried out by P. Fernández-Colón and E. Lacasa from the Conservation and Restoration Area of CENIEH-ICTS and L. López-Polín from IPHES. The picture of the specimen ATD6-92 was made by M. Modesto-Mata. E. Cappellini, J.C., J.V.O. and P. Gutenbrunner are supported by the Marie Skłodowska-Curie European Training Network (ETN) TEMPERA, a project funded by the European Union's Framework Program for Research and Innovation Horizon 2020 (grant agreement no. 722606). Amino acid analyses were undertaken thanks to the Leverhulme Trust (PLP-2012-116) and NERC (NE/K500987/1). T.M.-B. is supported by BFU2017-86471-P (MINECO/FEDER, UE), U01 MH106874 grant, Howard Hughes International Early Career, Obra Social 'La Caixa' and Secretaria d'Universitats i Recerca and CERCA Programme del Departament d'Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). C.L.-F. is supported by a FEDER-MINECO grant (PGC2018-095931-B-100). M.K. was supported by the Postdoctoral Junior Leader Fellowship Programme from 'la Caixa' Banking Foundation (LCF/BQ/PR19/11700002). M.M. is supported by the Danish National Research Foundation award PROTEIOS (DNRF128). Work at the Novo Nordisk Foundation Center for Protein Research is funded in part by a donation from the Novo Nordisk Foundation (grant number NNF14CC0001).
Changes in the epigenetic regulation of gene expression have a central role in evolution. Here, we extensively profiled a panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with whole genome sequencing (WGS) and whole genome bisulfite sequencing (WGBS). We annotated regulatory elements (RE) and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of RE in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers (gE) in the regulation of gene expression. We observe that most regulatory changes occur in weakly active gE. Remarkably, novel human-specific gE with weak activities are enriched in human-specific nucleotide changes. These elements appear in genes with signals of positive selection and human acceleration, tissue-specific expression, and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation. ; R.G.-P. was supported by a fellowship from MICINN (FPU13/01823). P.E.-C. was supported by a Formació de Personal Investigador fellowship from Generalitat de Catalunya (FI_B00122). M.K. was supported by a Deutsche Forschungsgemeinschaft (DFG) fellowship (KU 3467/1-1) and the Postdoctoral Junior Leader Fellowship Program from "la Caixa" Banking Foundation (LCF/BQ/PR19/11700002). D.J. was supported by a Juan de la Cierva fellowship (FJCI2016-29558) from MICINN. T.M-B. is supported by funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement EC-H2020-ERC-CoG-ApeGenomeDiversity-864203), BFU2017-86471-P (AEI/FEDER, UE), "Unidad de Excelencia María de Maeztu", funded by the AEI (CEX2018-000792-M), Howard Hughes International Early Career, NIH 1R01HG010898-01A1, Obra Social "La Caixa" and Secretaria d'Universitats i Recerca and CERCA Program del Departament d'Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). G.M., V.D.C., and L.D.C. were supported by grants from the Spanish of Economy, Industry, and Competitiveness (MEIC) (BFU2016-75008-P) and G.M. was also supported by the "Convocatoria de Ayudas Fundación BBVA a Investigadores, Innovadores y Creadores Culturales". J.L.G.-S. was supported by the Spanish government (grants BFU2016-74961-P), an institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 740041). A.N. was supported by Fondo Europeo de Desarrollo Regional (FEDER) with project grants BFU2016-77961-P and PGC2018- 101927-B-I00 and by the Spanish National Institute of Bioinformatics (PT17/0009/0020). ; With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2018-000792-M). ; 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).
Changes in the epigenetic regulation of gene expression have a central role in evolution. Here, we extensively profiled a panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with whole genome sequencing (WGS) and whole genome bisulfite sequencing (WGBS). We annotated regulatory elements (RE) and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of RE in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers (gE) in the regulation of gene expression. We observe that most regulatory changes occur in weakly active gE. Remarkably, novel human-specific gE with weak activities are enriched in human-specific nucleotide changes. These elements appear in genes with signals of positive selection and human acceleration, tissue-specific expression, and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation. ; R.G.-P. was supported by a fellowship from MICINN (FPU13/01823). P.E.-C. was supported by a Formació de Personal Investigador fellowship from Generalitat de Catalunya (FI_B00122). M.K. was supported by a Deutsche Forschungsgemeinschaft (DFG) fellowship (KU 3467/1-1) and the Postdoctoral Junior Leader Fellowship Program from "la Caixa" Banking Foundation (LCF/BQ/PR19/11700002). D.J. was supported by a Juan de la Cierva fellowship (FJCI2016-29558) from MICINN. T.M-B. is supported by funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement EC-H2020-ERC-CoG-ApeGenomeDiversity-864203), BFU2017-86471-P (AEI/FEDER, UE), "Unidad de Excelencia María de Maeztu", funded by the AEI (CEX2018-000792-M), Howard Hughes International Early Career, NIH 1R01HG010898-01A1, Obra Social "La Caixa" and Secretaria d'Universitats i Recerca and CERCA Program del Departament d'Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). G.M., V.D.C., and L.D.C. were supported by grants from the Spanish of Economy, Industry, and Competitiveness (MEIC) (BFU2016-75008-P) and G.M. was also supported by the "Convocatoria de Ayudas Fundación BBVA a Investigadores, Innovadores y Creadores Culturales". J.L.G.-S. was supported by the Spanish government (grants BFU2016-74961-P), an institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 740041). A.N. was supported by Fondo Europeo de Desarrollo Regional (FEDER) with project grants BFU2016-77961-P and PGC2018- 101927-B-I00 and by the Spanish National Institute of Bioinformatics (PT17/0009/0020).
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).
The European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 864203) (to T.M.-B.). BFU2017-86471-P (MINECO/FEDER, UE) (to T.M.-B.). "Unidad de Excelencia María de Maeztu", funded by the AEI (CEX2018-000792-M) (to T.M.-B.). Howard Hughes International Early Career (to T.M.-B.). NIH 1R01HG010898-01A1 (to T.M.-B.). Secretaria d'Universitats i Recerca and CERCA Program del Departament d'Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880) (to T.M.-B.). UCL's Wellcome Trust ISSF3 award 204841/Z/16/Z (to A.M.A. and J.M.S.). Generalitat de Catalunya (2017 SGR-1040) (to M. Llorente). Wellcome Trust Investigator Award 202802/Z/16/Z (to D.A.H.). The Pan African Program: The Cultured Chimpanzee (PanAf) is generously funded by the Max Planck Society, the Max Planck Society Innovation Fund, and the Heinz L. Krekeler Foundation. ; Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees (Pan troglodytes) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos (Pan paniscus). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees. ; Publisher PDF ; Peer reviewed
