Primate-specific spliced PMCHL RNAs are non-protein coding in human and macaque tissues

<p>Abstract</p> <p>Background</p> <p>Brain-expressed genes that were created in primate lineage represent obvious candidates to investigate molecular mechanisms that contributed to neural reorganization and emergence of new behavioural functions in <it>Homo sapiens</it>. <it>PMCHL1 </it>arose from retroposition of a pro-melanin-concentrating hormone (<it>PMCH</it>) antisense mRNA on the ancestral human chromosome 5p14 when platyrrhines and catarrhines diverged. Mutations before divergence of hylobatidae led to creation of new exons and finally <it>PMCHL1 </it>duplicated in an ancestor of hominids to generate <it>PMCHL2 </it>at the human chromosome 5q13. A complex pattern of spliced and unspliced <it>PMCHL </it>RNAs were found in human brain and testis.</p> <p>Results</p> <p>Several novel spliced <it>PMCHL </it>transcripts have been characterized in human testis and fetal brain, identifying an additional exon and novel splice sites. Sequencing of <it>PMCHL </it>genes in several non-human primates allowed to carry out phylogenetic analyses revealing that the initial retroposition event took place within an intron of the <it>brain cadherin </it>(<it>CDH12</it>) gene, soon after platyrrhine/catarrhine divergence, i.e. 30–35 Mya, and was concomitant with the insertion of an AluSg element. Sequence analysis of the spliced <it>PMCHL </it>transcripts identified only short ORFs of less than 300 bp, with low (VMCH-p8 and protein variants) or no evolutionary conservation. Western blot analyses of human and macaque tissues expressing <it>PMCHL </it>RNA failed to reveal any protein corresponding to VMCH-p8 and protein variants encoded by spliced transcripts.</p> <p>Conclusion</p> <p>Our present results improve our knowledge of the gene structure and the evolutionary history of the primate-specific chimeric <it>PMCHL </it>genes. These genes produce multiple spliced transcripts, bearing short, non-conserved and apparently non-translated ORFs that may function as mRNA-like non-coding RNAs.</p

Copy number variation analysis in the great apes reveals species-specific patterns of structural variation

Gazave, Elodie et al.Copy number variants (CNVs) are increasingly acknowledged as an important source of evolutionary novelties in the human lineage. However, our understanding of their significance is still hindered by the lack of primate CNV data. We performed intraspecific comparative genomic hybridizations to identify loci harboring copy number variants in each of the four great apes: bonobos, chimpanzees, gorillas, and orangutans. For the first time, we could analyze differences in CNV location and frequency in these four species, and compare them with human CNVs and primate segmental duplication (SD) maps. In addition, for bonobo and gorilla, patterns of CNV and nucleotide diversity were studied in the same individuals. We show that CNVs have been subject to different selective pressures in different lineages.Evidence for purifying selection is stronger in gorilla CNVs overlapping genes, while positive selection appears to have driven the fixation of structural variants in the orangutan lineage. In contrast, chimpanzees and bonobos present high levels of common structural polymorphism, which is indicative of relaxed purifying selection together with the higher mutation rates induced by the known burst of segmental duplication in the ancestor of the African apes. Indeed, the impact of the duplication burst is noticeable by the fact that bonobo and chimpanzee share more CNVs with gorilla than expected. Finally, we identified a number of interesting genomic regions that present high-frequency CNVs in all great apes, while containing only very rare or even pathogenic structural variants in humans.Financial support was provided by a Beatriu de Pinos postdoctoral Grant to E.G., the Spanish Ministry of Science and Innovation (Grant BFU2009-13409-02-02toA.N.),and the Spanish National Institute for Bioinformatics (INB, www.inab.org).Peer reviewe

Mucho más que un 1%: la verdadera cantidad de diferencias entre humanos y chimpancés

Este artículo trata de la diferencia del genoma de los humanos y de otras especies de primates. Este difiere en más de un 1%, lo que ha constituido una creencia común hasta este mismo año. En realidad, difieren hasta en un 10% y la naturaleza de estas diferencias es tal que bien podría haber sido la fuente más importante de novedad evolutiva y adaptación en nuestro linaj

Comparative and demographic analysis of orang-utan genomes

5 páginas, 5 figuras, 2 tablas.-- This paper is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike Licence, and is freely available to all readers atwww.nature.com/nature.-- et al.‘Orang-utan’ is derived from a Malay term meaning ‘man of the forest’ and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal1, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (Ne) expanded exponentially relative to the ancestral Ne after the split, while Bornean Ne declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.The orang-utan genome project was funded by the National Human Genome Research Institute (NHGRI), including grantsU54HG003079 (R.K.W.) and U54 HG003273 (R.A.G), with further support from National Institutes of Health R01 GM59290 (M.A.B.), PO1 AG022064 (M.A.B.), HG002385 (E.E.E.) and HG002238 (W.M.), National Science Foundation DBI-0644111 (A.S. and B.B.), David and Lucile Packard Foundation(A.S., V.T. and T.V.),CornellUniversity Provost’s Fellowship (A.L.M.), UK Medical Research Council (C.P.P., G.L., S.M. and A.H.), Marie Curie Fellowship (T.M.-B.), Ministerio de Ciencia e Innovación-Spain (MCI-Spain) and Fundación M. Botín (V.Q., X.S.P., G.R.O. and C.L.-O.), MCI-Spain BFU2006-15413-C02-01 and BFU2009-13409-C02-02 (A.N.), Spanish National Institute for Bioinformatics (INAB) and Fundação para a Ciência e a Tecnologia (Portugal), SFRH/BPD/26384/2006(R.F.) and SFRH/BD/15856/2005 (O.F.), PRIN and CEGBA (M.R., N.A. and G.D.V.), and the Commission of the European Communities IRG-224885 (T.V.), IRG-231025 (B.B.).Peer reviewe

Les établissements ruraux du Hallstatt D2 et D3 de Ville-Saint-Jacques « Le Bois d’Echalas » (Seine-et-Marne)

International audienc

Genome-wide analysis of wild-type epstein-barr virus genomes derived from healthy individuals of the 1000 genomes project

Trabajo presentado en la 4th Meeting of the Spanish Society of the Evolutionary Biology (SESBE 2013) celebrada en Barcelona del 27 al 29 de noviembre de 2013.Most people in the world (~90%) are infected by the Epstein-Barr virus (EBV), which establishes itself permanently in B-cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis and different types of cancer. So far, only seven complete EBV strains have been described, all of them coming from donors presenting EBV-related diseases.To perform a detailed comparative genomics analysis of EBV including, for the first time, EBV strains derived from healthy individuals we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project. Since strain B95-8 was used to transform B-cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains. After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV. By mapping the natural EBV reads into the EBV reference genome (NC007605) we constructed wild-type viral genomes from three individuals.Analysis of all the available sequences reveals a complex history of recombination among EBV strains and that latency genes harbour more nucleotide diversity than lytic genes. Six out of nine latency-related genes present the molecular signature of positive selection, suggesting rapid host-parasite co-evolution.Peer reviewe

Copy number variation analysis in the great apes reveals species-specific patterns of structural variation

Copy number variants (CNVs) are increasingly acknowledged as an important source of evolutionary novelties in the human lineage. However, our understanding of their significance is still hindered by the lack of primate CNV data. We performed intraspecific comparative genomic hybridizations to identify loci harboring copy number variants in each of the four great apes: bonobos, chimpanzees, gorillas, and orangutans. For the first time, we could analyze differences in CNV location and frequency in these four species, and compare them with human CNVs and primate segmental duplication (SD) maps. In addition, for bonobo and gorilla, patterns of CNV and nucleotide diversity were studied in the same individuals. We show that CNVs have been subject to different selective pressures in different lineages. Evidence for purifying selection is stronger in gorilla CNVs overlapping genes, while positive selection appears to have driven the fixation of structural variants in the orangutan lineage. In contrast, chimpanzees and bonobos present high levels of common structural polymorphism, which is indicative of relaxed purifying selection together with the higher mutation rates induced by the known burst of segmental duplication in the ancestor of the African apes. Indeed, the impact of the duplication burst is noticeable by the fact that bonobo and chimpanzee share more CNVs with gorilla than expected. Finally, we identified a number of interesting genomic regions that present high-frequency CNVs in all great apes, while containing only very rare or even pathogenic structural variants in humans

Comparative and demographic analysis of orang-utan genomes

none101siOrang-utan- is derived from a Malay term meaning man of the forest- and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N e) expanded exponentially relative to the ancestral N e after the split, while Bornean N e declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts. © 2011 Macmillan Publishers Limited. All rights reserved.noneLocke, Devin P; Hillier, Ladeana W.; Warren, Wesley C.; Worley, Kim C.; Nazareth, Lynne V.; Muzny, Donna M.; Yang, Shiaw-Pyng; Wang, Zhengyuan; Chinwalla, Asif T.; Minx, Pat; Mitreva, Makedonka; Cook, Lisa; Delehaunty, Kim D.; Fronick, Catrina; Schmidt, Heather; Fulton, Lucinda A.; Fulton, Robert S.; Nelson, Joanne O.; Magrini, Vincent; Pohl, Craig; Graves, Tina A.; Markovic, Chris; Cree, Andy; Dinh, Huyen H.; Hume, Jennifer; Kovar, Christie L.; Fowler, Gerald R.; Lunter, Gerton; Meader, Stephen; Heger, Andreas; Ponting, Chris P.; Marques-Bonet, Tomas; Alkan, Can; Chen, Lin; Cheng, Ze; Kidd, Jeffrey M.; Eichler, Evan E.; White, Simon; Searle, Stephen; Vilella, Albert J.; Chen, Yuan; Flicek, Paul; Ma, Jian; Raney, Brian; Suh, Bernard; Burhans, Richard; Herrero, Javier; Haussler, David; Faria, Rui; Fernando, Olga; Darré, Fleur; Farré, Doménec; Gazave, Elodie; Oliva, Meritxell; Navarro, Arcadi; Roberto, Roberta; Capozzi, Oronzo; Archidiacono, Nicoletta; Della Valle, Giuliano; Purgato, Stefania; Rocchi, Mariano; Konkel, Miriam K.; Walker, Jerilyn A.; Ullmer, Brygg; Batzer, Mark A.; Smit, Arian F. A.; Hubley, Robert; Casola, Claudio; Schrider, Daniel R.; Hahn, Matthew W.; Quesada, Victor; Puente, Xose S.; Ordõez, Gonzalo R.; Ĺpez-Otín, Carlos; Vinar, Tomas; Brejova, Brona; Ratan, Aakrosh; Harris, Robert S.; Miller, Webb; Kosiol, Carolin; Lawson, Heather A.; Taliwal, Vikas; Martins, André L.; Siepel, Adam; Roychoudhury, Arindam; Ma, Xin; Degenhardt, Jeremiah; Bustamante, Carlos D.; Gutenkunst, Ryan N.; Mailund, Thomas; Dutheil, Julien Y.; Hobolth, Asger; Schierup, Mikkel H.; Ryder, Oliver A.; Yoshinaga, Yuko; De Jong, Pieter J.; Weinstock, George M.; Rogers, Jeffrey; Mardis, Elaine R.; Gibbs, Richard A.; Wilson, Richard K.Locke, Devin P; Hillier, Ladeana W.; Warren, Wesley C.; Worley, Kim C.; Nazareth, Lynne V.; Muzny, Donna M.; Yang, Shiaw-Pyng; Wang, Zhengyuan; Chinwalla, Asif T.; Minx, Pat; Mitreva, Makedonka; Cook, Lisa; Delehaunty, Kim D.; Fronick, Catrina; Schmidt, Heather; Fulton, Lucinda A.; Fulton, Robert S.; Nelson, Joanne O.; Magrini, Vincent; Pohl, Craig; Graves, Tina A.; Markovic, Chris; Cree, Andy; Dinh, Huyen H.; Hume, Jennifer; Kovar, Christie L.; Fowler, Gerald R.; Lunter, Gerton; Meader, Stephen; Heger, Andreas; Ponting, Chris P.; Marques-Bonet, Tomas; Alkan, Can; Chen, Lin; Cheng, Ze; Kidd, Jeffrey M.; Eichler, Evan E.; White, Simon; Searle, Stephen; Vilella, Albert J.; Chen, Yuan; Flicek, Paul; Ma, Jian; Raney, Brian; Suh, Bernard; Burhans, Richard; Herrero, Javier; Haussler, David; Faria, Rui; Fernando, Olga; Darré, Fleur; Farré, Doménec; Gazave, Elodie; Oliva, Meritxell; Navarro, Arcadi; Roberto, Roberta; Capozzi, Oronzo; Archidiacono, Nicoletta; Della Valle, Giuliano; Purgato, Stefania; Rocchi, Mariano; Konkel, Miriam K.; Walker, Jerilyn A.; Ullmer, Brygg; Batzer, Mark A.; Smit, Arian F. A.; Hubley, Robert; Casola, Claudio; Schrider, Daniel R.; Hahn, Matthew W.; Quesada, Victor; Puente, Xose S.; Ordõez, Gonzalo R.; Ĺpez-Otín, Carlos; Vinar, Tomas; Brejova, Brona; Ratan, Aakrosh; Harris, Robert S.; Miller, Webb; Kosiol, Carolin; Lawson, Heather A.; Taliwal, Vikas; Martins, André L.; Siepel, Adam; Roychoudhury, Arindam; Ma, Xin; Degenhardt, Jeremiah; Bustamante, Carlos D.; Gutenkunst, Ryan N.; Mailund, Thomas; Dutheil, Julien Y.; Hobolth, Asger; Schierup, Mikkel H.; Ryder, Oliver A.; Yoshinaga, Yuko; De Jong, Pieter J.; Weinstock, George M.; Rogers, Jeffrey; Mardis, Elaine R.; Gibbs, Richard A.; Wilson, Richard K