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713 results on '"Palma, Federica"'

2. Vocal learning-associated convergent evolution in mammalian proteins and regulatory elements.

Author

Wirthlin, Morgan, Schmid, Tobias, Elie, Julie, Zhang, Xiaomeng, Kowalczyk, Amanda, Redlich, Ruby, Shvareva, Varvara, Rakuljic, Ashley, Ji, Maria, Bhat, Ninad, Kaplow, Irene, Schäffer, Daniel, Lawler, Alyssa, Wang, Andrew, Phan, BaDoi, Annaldasula, Siddharth, Brown, Ashley, Lu, Tianyu, Lim, Byung, Azim, Eiman, Clark, Nathan, Meyer, Wynn, Pond, Sergei, Chikina, Maria, Yartsev, Michael, Pfenning, Andreas, Andrews, Gregory, Armstrong, Joel, Bianchi, Matteo, Birren, Bruce, Bredemeyer, Kevin, Breit, Ana, Christmas, Matthew, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole, Forsberg-Nilsson, Karin, Garcia, Carlos, Gatesy, John, Gazal, Steven, Genereux, Diane, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela, Harris, Andrew, Hickey, Glenn, Hiller, Michael, Hindle, Allyson, Hubley, Robert, Hughes, Graham, Johnson, Jeremy, Juan, David, Karlsson, Elinor, Keough, Kathleen, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer, Kozyrev, Sergey, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle, Lewin, Harris, Li, Xue, Lind, Abigail, Lindblad-Toh, Kerstin, Mackay-Smith, Ava, Marinescu, Voichita, Marques-Bonet, Tomas, Mason, Victor, Meadows, Jennifer, Moore, Jill, Moreira, Lucas, Moreno-Santillan, Diana, Morrill, Kathleen, Muntané, Gerard, Murphy, William, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole, Pollard, Katherine, Pratt, Henry, Ray, David, Reilly, Steven, Rosen, Jeb, and Ruf, Irina

Subjects
Animals, Chiroptera, Vocalization, Animal, Motor Cortex, Chromatin, Enhancer Elements, Genetic, Motor Neurons, Larynx, Epigenesis, Genetic, Genome, Gene Expression Regulation, Evolution, Molecular, Proteins, Amino Acid Sequence, Eutheria, Machine Learning
Abstract

Vocal production learning (vocal learning) is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.

Published
2024

4. A genomic timescale for placental mammal evolution

Author

Foley, Nicole M, Mason, Victor C, Harris, Andrew J, Bredemeyer, Kevin R, Damas, Joana, Lewin, Harris A, Eizirik, Eduardo, Gatesy, John, Karlsson, Elinor K, Lindblad-Toh, Kerstin, Springer, Mark S, Murphy, William J, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Fan, Kaili, Fanter, Cornelia, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, Steiner, Cynthia, Storer, Jessica M, Sullivan, Kevin AM, Sullivan, Patrick F, and Sundström, Elisabeth

Subjects
Genetics, Human Genome, Biotechnology, Animals, Female, Biological Evolution, Eutheria, Evolution, Molecular, Fossils, Genomics, Phylogeny, Genetic Variation, Time Factors, Zoonomia Consortium‡, General Science & Technology
Abstract

The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis of genetic variation across an alignment of 241 placental mammal genome assemblies, addressing prior concerns regarding limited genomic sampling across species. We compared neutral genome-wide phylogenomic signals using concatenation and coalescent-based approaches, interrogated phylogenetic variation across chromosomes, and analyzed extensive catalogs of structural variants. Interordinal relationships exhibit relatively low rates of phylogenomic conflict across diverse datasets and analytical methods. Conversely, X-chromosome versus autosome conflicts characterize multiple independent clades that radiated during the Cenozoic. Genomic time trees reveal an accumulation of cladogenic events before and immediately after the Cretaceous-Paleogene (K-Pg) boundary, implying important roles for Cretaceous continental vicariance and the K-Pg extinction in the placental radiation.

Published
2023

5. Comparative genomics of Balto, a famous historic dog, captures lost diversity of 1920s sled dogs

Author

Moon, Katherine L, Huson, Heather J, Morrill, Kathleen, Wang, Ming-Shan, Li, Xue, Srikanth, Krishnamoorthy, Lindblad-Toh, Kerstin, Svenson, Gavin J, Karlsson, Elinor K, Shapiro, Beth, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, Steiner, Cynthia, Storer, Jessica M, Sullivan, Kevin AM, Sullivan, Patrick F, Sundström, Elisabeth, Supple, Megan A, and Swofford, Ross

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Genetics, Animals, Dogs, Male, Genome, Genomics, Genotype, Phenotype, Wolves, Biodiversity, Genetic Variation, Zoonomia Consortium, General Science & Technology
Abstract

We reconstruct the phenotype of Balto, the heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from the Zoonomia alignment of 240 mammals and 682 genomes from dogs and wolves of the 21st century. Balto shares just part of his diverse ancestry with the eponymous Siberian husky breed. Balto's genotype predicts a combination of coat features atypical for modern sled dog breeds, and a slightly smaller stature. He had enhanced starch digestion compared with Greenland sled dogs and a compendium of derived homozygous coding variants at constrained positions in genes connected to bone and skin development. We propose that Balto's population of origin, which was less inbred and genetically healthier than that of modern breeds, was adapted to the extreme environment of 1920s Alaska.

Published
2023

6. The contribution of historical processes to contemporary extinction risk in placental mammals

Author

Wilder, Aryn P, Supple, Megan A, Subramanian, Ayshwarya, Mudide, Anish, Swofford, Ross, Serres-Armero, Aitor, Steiner, Cynthia, Koepfli, Klaus-Peter, Genereux, Diane P, Karlsson, Elinor K, Lindblad-Toh, Kerstin, Marques-Bonet, Tomas, Munoz Fuentes, Violeta, Foley, Kathleen, Meyer, Wynn K, Ryder, Oliver A, Shapiro, Beth, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Mason, Victor C, Meadows, Jennifer RS, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Smit, Arian FA, Springer, Mark, and Srinivasan, Chaitanya

Subjects
Biological Sciences, Evolutionary Biology, Genetics, Behavioral and Social Science, Human Genome, Basic Behavioral and Social Science, Life on Land, Animals, Female, Pregnancy, Eutheria, Extinction, Biological, Genetic Variation, Genome, Population Density, Risk, Zoonomia Consortium‡, General Science & Technology
Abstract

Species persistence can be influenced by the amount, type, and distribution of diversity across the genome, suggesting a potential relationship between historical demography and resilience. In this study, we surveyed genetic variation across single genomes of 240 mammals that compose the Zoonomia alignment to evaluate how historical effective population size (Ne) affects heterozygosity and deleterious genetic load and how these factors may contribute to extinction risk. We find that species with smaller historical Ne carry a proportionally larger burden of deleterious alleles owing to long-term accumulation and fixation of genetic load and have a higher risk of extinction. This suggests that historical demography can inform contemporary resilience. Models that included genomic data were predictive of species' conservation status, suggesting that, in the absence of adequate census or ecological data, genomic information may provide an initial risk assessment.

Published
2023

7. The functional and evolutionary impacts of human-specific deletions in conserved elements

Author

Xue, James R, Mackay-Smith, Ava, Mouri, Kousuke, Garcia, Meilin Fernandez, Dong, Michael X, Akers, Jared F, Noble, Mark, Li, Xue, Lindblad-Toh, Kerstin, Karlsson, Elinor K, Noonan, James P, Capellini, Terence D, Brennand, Kristen J, Tewhey, Ryan, Sabeti, Pardis C, Reilly, Steven K, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Lind, Abigail, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Schäffer, Daniel E, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, and Steiner, Cynthia

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Biotechnology, Neurosciences, Human Genome, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Neurological, Humans, Conserved Sequence, Evolution, Molecular, Genome, Genomics, RNA-Binding Proteins, Sequence Deletion, Brain, Gene Expression Regulation, Developmental, Zoonomia Consortium†, General Science & Technology
Abstract

Conserved genomic sequences disrupted in humans may underlie uniquely human phenotypic traits. We identified and characterized 10,032 human-specific conserved deletions (hCONDELs). These short (average 2.56 base pairs) deletions are enriched for human brain functions across genetic, epigenomic, and transcriptomic datasets. Using massively parallel reporter assays in six cell types, we discovered 800 hCONDELs conferring significant differences in regulatory activity, half of which enhance rather than disrupt regulatory function. We highlight several hCONDELs with putative human-specific effects on brain development, including HDAC5, CPEB4, and PPP2CA. Reverting an hCONDEL to the ancestral sequence alters the expression of LOXL2 and developmental genes involved in myelination and synaptic function. Our data provide a rich resource to investigate the evolutionary mechanisms driving new traits in humans and other species.

Published
2023

8. Integrating gene annotation with orthology inference at scale

Author

Kirilenko, Bogdan M, Munegowda, Chetan, Osipova, Ekaterina, Jebb, David, Sharma, Virag, Blumer, Moritz, Morales, Ariadna E, Ahmed, Alexis-Walid, Kontopoulos, Dimitrios-Georgios, Hilgers, Leon, Lindblad-Toh, Kerstin, Karlsson, Elinor K, Hiller, Michael, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, Steiner, Cynthia, Storer, Jessica M, Sullivan, Kevin AM, and Sullivan, Patrick F

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Biotechnology, Human Genome, Generic health relevance, Animals, Female, Mice, Eutheria, Genome, Genomics, Molecular Sequence Annotation, Birds, Zoonomia Consortium‡, General Science & Technology
Abstract

Annotating coding genes and inferring orthologs are two classical challenges in genomics and evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA (Tool to infer Orthologs from Genome Alignments), a method that integrates structural gene annotation and orthology inference. TOGA implements a different paradigm to infer orthologous loci, improves ortholog detection and annotation of conserved genes compared with state-of-the-art methods, and handles even highly fragmented assemblies. TOGA scales to hundreds of genomes, which we demonstrate by applying it to 488 placental mammal and 501 bird assemblies, creating the largest comparative gene resources so far. Additionally, TOGA detects gene losses, enables selection screens, and automatically provides a superior measure of mammalian genome quality. TOGA is a powerful and scalable method to annotate and compare genes in the genomic era.

Published
2023

9. Relating enhancer genetic variation across mammals to complex phenotypes using machine learning

Author

Kaplow, Irene M, Lawler, Alyssa J, Schäffer, Daniel E, Srinivasan, Chaitanya, Sestili, Heather H, Wirthlin, Morgan E, Phan, BaDoi N, Prasad, Kavya, Brown, Ashley R, Zhang, Xiaomeng, Foley, Kathleen, Genereux, Diane P, Karlsson, Elinor K, Lindblad-Toh, Kerstin, Meyer, Wynn K, Pfenning, Andreas R, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, and Steiner, Cynthia

Subjects
Biological Sciences, Genetics, Pediatric, Human Genome, Rare Diseases, Congenital Structural Anomalies, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Mental health, Animals, Enhancer Elements, Genetic, Genetic Variation, Machine Learning, Mammals, Phenotype, Zoonomia Consortium**, General Science & Technology
Abstract

Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations between enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent and functionally conserved despite low sequence conservation. We developed the Tissue-Aware Conservation Inference Toolkit (TACIT) to associate candidate enhancers with species' phenotypes using predictions from machine learning models trained on specific tissues. Applying TACIT to associate motor cortex and parvalbumin-positive interneuron enhancers with neurological phenotypes revealed dozens of enhancer-phenotype associations, including brain size-associated enhancers that interact with genes implicated in microcephaly or macrocephaly. TACIT provides a foundation for identifying enhancers associated with the evolution of any convergently evolved phenotype in any large group of species with aligned genomes.

Published
2023

10. Three-dimensional genome rewiring in loci with human accelerated regions

Author

Keough, Kathleen C, Whalen, Sean, Inoue, Fumitaka, Przytycki, Pawel F, Fair, Tyler, Deng, Chengyu, Steyert, Marilyn, Ryu, Hane, Lindblad-Toh, Kerstin, Karlsson, Elinor, Nowakowski, Tomasz, Ahituv, Nadav, Pollen, Alex, Pollard, Katherine S, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Karlsson, Elinor K, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, Steiner, Cynthia, Storer, Jessica M, and Sullivan, Kevin AM

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Stem Cell Research, Human Genome, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Animals, Humans, Chromatin, Genome, Human, Genomics, Pan troglodytes, Genetic Loci, Neurogenesis, Deep Learning, Zoonomia Consortium§, General Science & Technology
Abstract

Human accelerated regions (HARs) are conserved genomic loci that evolved at an accelerated rate in the human lineage and may underlie human-specific traits. We generated HARs and chimpanzee accelerated regions with an automated pipeline and an alignment of 241 mammalian genomes. Combining deep learning with chromatin capture experiments in human and chimpanzee neural progenitor cells, we discovered a significant enrichment of HARs in topologically associating domains containing human-specific genomic variants that change three-dimensional (3D) genome organization. Differential gene expression between humans and chimpanzees at these loci suggests rewiring of regulatory interactions between HARs and neurodevelopmental genes. Thus, comparative genomics together with models of 3D genome folding revealed enhancer hijacking as an explanation for the rapid evolution of HARs.

Published
2023

11. Evolutionary constraint and innovation across hundreds of placental mammals

Author

Christmas, Matthew J, Kaplow, Irene M, Genereux, Diane P, Dong, Michael X, Hughes, Graham M, Li, Xue, Sullivan, Patrick F, Hindle, Allyson G, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Breit, Ana M, Diekhans, Mark, Fanter, Cornelia, Foley, Nicole M, Goodman, Daniel B, Goodman, Linda, Keough, Kathleen C, Kirilenko, Bogdan, Kowalczyk, Amanda, Lawless, Colleen, Lind, Abigail L, Meadows, Jennifer RS, Moreira, Lucas R, Redlich, Ruby W, Ryan, Louise, Swofford, Ross, Valenzuela, Alejandro, Wagner, Franziska, Wallerman, Ola, Brown, Ashley R, Damas, Joana, Fan, Kaili, Gatesy, John, Grimshaw, Jenna, Johnson, Jeremy, Kozyrev, Sergey V, Lawler, Alyssa J, Marinescu, Voichita D, Morrill, Kathleen M, Osmanski, Austin, Paulat, Nicole S, Phan, BaDoi N, Reilly, Steven K, Schäffer, Daniel E, Steiner, Cynthia, Supple, Megan A, Wilder, Aryn P, Wirthlin, Morgan E, Xue, James R, Birren, Bruce W, Gazal, Steven, Hubley, Robert M, Koepfli, Klaus-Peter, Marques-Bonet, Tomas, Meyer, Wynn K, Nweeia, Martin, Sabeti, Pardis C, Shapiro, Beth, Smit, Arian FA, Springer, Mark S, Teeling, Emma C, Weng, Zhiping, Hiller, Michael, Levesque, Danielle L, Lewin, Harris A, Murphy, William J, Navarro, Arcadi, Paten, Benedict, Pollard, Katherine S, Ray, David A, Ruf, Irina, Ryder, Oliver A, Pfenning, Andreas R, Lindblad-Toh, Kerstin, Karlsson, Elinor K, Bredemeyer, Kevin R, Clawson, Hiram, Di Palma, Federica, Eizirik, Eduardo, Forsberg-Nilsson, Karin, Garcia, Carlos J, and Halsey, Michaela K

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Generic health relevance, Animals, Female, Humans, Conserved Sequence, Eutheria, Evolution, Molecular, Genome, Human, Zoonomia Consortium§, General Science & Technology
Abstract

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.

Published
2023

12. Leveraging base-pair mammalian constraint to understand genetic variation and human disease

Author

Sullivan, Patrick F, Meadows, Jennifer RS, Gazal, Steven, Phan, BaDoi N, Li, Xue, Genereux, Diane P, Dong, Michael X, Bianchi, Matteo, Andrews, Gregory, Sakthikumar, Sharadha, Nordin, Jessika, Roy, Ananya, Christmas, Matthew J, Marinescu, Voichita D, Wang, Chao, Wallerman, Ola, Xue, James, Yao, Shuyang, Sun, Quan, Szatkiewicz, Jin, Wen, Jia, Huckins, Laura M, Lawler, Alyssa, Keough, Kathleen C, Zheng, Zhili, Zeng, Jian, Wray, Naomi R, Li, Yun, Johnson, Jessica, Chen, Jiawen, Paten, Benedict, Reilly, Steven K, Hughes, Graham M, Weng, Zhiping, Pollard, Katherine S, Pfenning, Andreas R, Forsberg-Nilsson, Karin, Karlsson, Elinor K, Lindblad-Toh, Kerstin, Armstrong, Joel C, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Garcia, Carlos J, Gatesy, John, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Lind, Abigail, Mackay-Smith, Ava, Marques-Bonet, Tomas, Mason, Victor C, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, and Navarro, Arcadi

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Biotechnology, Clinical Research, Human Genome, Brain Disorders, Generic health relevance, Animals, Humans, Biological Evolution, Genetic Variation, Genome, Human, Genome-Wide Association Study, Genomics, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Disease, Zoonomia Consortium§, General Science & Technology
Abstract

Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.

Published
2023

13. Evolution of the ancestral mammalian karyotype and syntenic regions

Author

Damas, Joana, Corbo, Marco, Kim, Jaebum, Turner-Maier, Jason, Farré, Marta, Larkin, Denis M, Ryder, Oliver A, Steiner, Cynthia, Houck, Marlys L, Hall, Shaune, Shiue, Lily, Thomas, Stephen, Swale, Thomas, Daly, Mark, Korlach, Jonas, Uliano-Silva, Marcela, Mazzoni, Camila J, Birren, Bruce W, Genereux, Diane P, Johnson, Jeremy, Lindblad-Toh, Kerstin, Karlsson, Elinor K, Nweeia, Martin T, Johnson, Rebecca N, Lewin, Harris A, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, and Ryan, Louise

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Evolutionary Biology, Genetics, Human Genome, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Cattle, Chromosomes, Mammalian, Eutheria, Evolution, Molecular, Humans, Karyotype, Mammals, Phylogeny, Sloths, Synteny, chromosome evolution, mammals, synteny conservation, ancestral genome reconstruction, topologically associating domains, Zoonomia Consortium
Abstract

Decrypting the rearrangements that drive mammalian chromosome evolution is critical to understanding the molecular bases of speciation, adaptation, and disease susceptibility. Using 8 scaffolded and 26 chromosome-scale genome assemblies representing 23/26 mammal orders, we computationally reconstructed ancestral karyotypes and syntenic relationships at 16 nodes along the mammalian phylogeny. Three different reference genomes (human, sloth, and cattle) representing phylogenetically distinct mammalian superorders were used to assess reference bias in the reconstructed ancestral karyotypes and to expand the number of clades with reconstructed genomes. The mammalian ancestor likely had 19 pairs of autosomes, with nine of the smallest chromosomes shared with the common ancestor of all amniotes (three still conserved in extant mammals), demonstrating a striking conservation of synteny for ∼320 My of vertebrate evolution. The numbers and types of chromosome rearrangements were classified for transitions between the ancestral mammalian karyotype, descendent ancestors, and extant species. For example, 94 inversions, 16 fissions, and 14 fusions that occurred over 53 My differentiated the therian from the descendent eutherian ancestor. The highest breakpoint rate was observed between the mammalian and therian ancestors (3.9 breakpoints/My). Reconstructed mammalian ancestor chromosomes were found to have distinct evolutionary histories reflected in their rates and types of rearrangements. The distributions of genes, repetitive elements, topologically associating domains, and actively transcribed regions in multispecies homologous synteny blocks and evolutionary breakpoint regions indicate that purifying selection acted over millions of years of vertebrate evolution to maintain syntenic relationships of developmentally important genes and regulatory landscapes of gene-dense chromosomes.

Published
2022

14. Standards recommendations for the Earth BioGenome Project

Author

Lawniczak, Mara KN, Durbin, Richard, Flicek, Paul, Lindblad-Toh, Kerstin, Wei, Xiaofeng, Archibald, John M, Baker, William J, Belov, Katherine, Blaxter, Mark L, Bonet, Tomas Marques, Childers, Anna K, Coddington, Jonathan A, Crandall, Keith A, Crawford, Andrew J, Davey, Robert P, Di Palma, Federica, Fang, Qi, Haerty, Wilfried, Hall, Neil, Hoff, Katharina J, Howe, Kerstin, Jarvis, Erich D, Johnson, Warren E, Johnson, Rebecca N, Kersey, Paul J, Liu, Xin, Lopez, Jose Victor, Myers, Eugene W, Pettersson, Olga Vinnere, Phillippy, Adam M, Poelchau, Monica F, Pruitt, Kim D, Rhie, Arang, Castilla-Rubio, Juan Carlos, Sahu, Sunil Kumar, Salmon, Nicholas A, Soltis, Pamela S, Swarbreck, David, Thibaud-Nissen, Françoise, Wang, Sibo, Wegrzyn, Jill L, Zhang, Guojie, Zhang, He, Lewin, Harris A, and Richards, Stephen

Subjects
Human Genome, Genetics, Animals, Base Sequence, Biodiversity, Eukaryota, Genomics, Humans, Reference Standards, Reference Values, Sequence Analysis, DNA, Earth BioGenome Project, genomics, ethics, genome assembly
Abstract

A global international initiative, such as the Earth BioGenome Project (EBP), requires both agreement and coordination on standards to ensure that the collective effort generates rapid progress toward its goals. To this end, the EBP initiated five technical standards committees comprising volunteer members from the global genomics scientific community: Sample Collection and Processing, Sequencing and Assembly, Annotation, Analysis, and IT and Informatics. The current versions of the resulting standards documents are available on the EBP website, with the recognition that opportunities, technologies, and challenges may improve or change in the future, requiring flexibility for the EBP to meet its goals. Here, we describe some highlights from the proposed standards, and areas where additional challenges will need to be met.

Published
2022

15. Why sequence all eukaryotes?

Author

Blaxter, Mark, Archibald, John M, Childers, Anna K, Coddington, Jonathan A, Crandall, Keith A, Di Palma, Federica, Durbin, Richard, Edwards, Scott V, Graves, Jennifer AM, Hackett, Kevin J, Hall, Neil, Jarvis, Erich D, Johnson, Rebecca N, Karlsson, Elinor K, Kress, W John, Kuraku, Shigehiro, Lawniczak, Mara KN, Lindblad-Toh, Kerstin, Lopez, Jose V, Moran, Nancy A, Robinson, Gene E, Ryder, Oliver A, Shapiro, Beth, Soltis, Pamela S, Warnow, Tandy, Zhang, Guojie, and Lewin, Harris A

Subjects
Biotechnology, Animals, Base Sequence, Biodiversity, Biological Evolution, Ecology, Ecosystem, Eukaryota, Genome, Genomics, Humans, Phylogeny, genome, diversity, ecology, evolution, conservation
Abstract

Life on Earth has evolved from initial simplicity to the astounding complexity we experience today. Bacteria and archaea have largely excelled in metabolic diversification, but eukaryotes additionally display abundant morphological innovation. How have these innovations come about and what constraints are there on the origins of novelty and the continuing maintenance of biodiversity on Earth? The history of life and the code for the working parts of cells and systems are written in the genome. The Earth BioGenome Project has proposed that the genomes of all extant, named eukaryotes-about 2 million species-should be sequenced to high quality to produce a digital library of life on Earth, beginning with strategic phylogenetic, ecological, and high-impact priorities. Here we discuss why we should sequence all eukaryotic species, not just a representative few scattered across the many branches of the tree of life. We suggest that many questions of evolutionary and ecological significance will only be addressable when whole-genome data representing divergences at all of the branchings in the tree of life or all species in natural ecosystems are available. We envisage that a genomic tree of life will foster understanding of the ongoing processes of speciation, adaptation, and organismal dependencies within entire ecosystems. These explorations will resolve long-standing problems in phylogenetics, evolution, ecology, conservation, agriculture, bioindustry, and medicine.

Published
2022

17. 3D genomics across the tree of life reveals condensin II as a determinant of architecture type

Author

Hoencamp, Claire, Dudchenko, Olga, Elbatsh, Ahmed MO, Brahmachari, Sumitabha, Raaijmakers, Jonne A, van Schaik, Tom, Sedeño Cacciatore, Ángela, Contessoto, Vinícius G, van Heesbeen, Roy GHP, van den Broek, Bram, Mhaskar, Aditya N, Teunissen, Hans, St Hilaire, Brian Glenn, Weisz, David, Omer, Arina D, Pham, Melanie, Colaric, Zane, Yang, Zhenzhen, Rao, Suhas SP, Mitra, Namita, Lui, Christopher, Yao, Weijie, Khan, Ruqayya, Moroz, Leonid L, Kohn, Andrea, St Leger, Judy, Mena, Alexandria, Holcroft, Karen, Gambetta, Maria Cristina, Lim, Fabian, Farley, Emma, Stein, Nils, Haddad, Alexander, Chauss, Daniel, Mutlu, Ayse Sena, Wang, Meng C, Young, Neil D, Hildebrandt, Evin, Cheng, Hans H, Knight, Christopher J, Burnham, Theresa LU, Hovel, Kevin A, Beel, Andrew J, Mattei, Pierre-Jean, Kornberg, Roger D, Warren, Wesley C, Cary, Gregory, Gómez-Skarmeta, José Luis, Hinman, Veronica, Lindblad-Toh, Kerstin, Di Palma, Federica, Maeshima, Kazuhiro, Multani, Asha S, Pathak, Sen, Nel-Themaat, Liesl, Behringer, Richard R, Kaur, Parwinder, Medema, René H, van Steensel, Bas, de Wit, Elzo, Onuchic, José N, Di Pierro, Michele, Lieberman Aiden, Erez, and Rowland, Benjamin D

Subjects
Human Genome, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Adenosine Triphosphatases, Algorithms, Animals, Biological Evolution, Cell Nucleolus, Cell Nucleus, Centromere, Chromosomes, Chromosomes, Human, DNA-Binding Proteins, Eukaryota, Genome, Genome, Human, Genomics, Heterochromatin, Humans, Interphase, Mitosis, Models, Biological, Multiprotein Complexes, Telomere, General Science & Technology
Abstract

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.

Published
2021

19. A comparative genomics multitool for scientific discovery and conservation

Author

Genereux, Diane P, Serres, Aitor, Armstrong, Joel, Johnson, Jeremy, Marinescu, Voichita D, Murén, Eva, Juan, David, Bejerano, Gill, Casewell, Nicholas R, Chemnick, Leona G, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Fiddes, Ian T, Garber, Manuel, Gladyshev, Vadim N, Goodman, Linda, Haerty, Wilfried, Houck, Marlys L, Hubley, Robert, Kivioja, Teemu, Koepfli, Klaus-Peter, Kuderna, Lukas FK, Lander, Eric S, Meadows, Jennifer RS, Murphy, William J, Nash, Will, Noh, Hyun Ji, Nweeia, Martin, Pfenning, Andreas R, Pollard, Katherine S, Ray, David A, Shapiro, Beth, Smit, Arian FA, Springer, Mark S, Steiner, Cynthia C, Swofford, Ross, Taipale, Jussi, Teeling, Emma C, Turner-Maier, Jason, Alfoldi, Jessica, Birren, Bruce, Ryder, Oliver A, Lewin, Harris A, Paten, Benedict, Marques-Bonet, Tomas, Lindblad-Toh, Kerstin, and Karlsson, Elinor K

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Ecology, Evolutionary Biology, Genetics, Human Genome, Biotechnology, Generic health relevance, Life on Land, Animals, Biodiversity, Biomedical Research, Conservation of Natural Resources, Eutheria, Evolution, Molecular, Extinction, Biological, Genetic Speciation, Genetic Variation, Genomics, Humans, Infections, Knowledge Discovery, Loss of Heterozygosity, Neoplasms, Phylogeny, Risk Assessment, Selection, Genetic, Sequence Alignment, Species Specificity, Venoms, Zoonomia Consortium, General Science & Technology
Abstract

The Zoonomia Project is investigating the genomics of shared and specialized traits in eutherian mammals. Here we provide genome assemblies for 131 species, of which all but 9 are previously uncharacterized, and describe a whole-genome alignment of 240 species of considerable phylogenetic diversity, comprising representatives from more than 80% of mammalian families. We find that regions of reduced genetic diversity are more abundant in species at a high risk of extinction, discern signals of evolutionary selection at high resolution and provide insights from individual reference genomes. By prioritizing phylogenetic diversity and making data available quickly and without restriction, the Zoonomia Project aims to support biological discovery, medical research and the conservation of biodiversity.

Published
2020

26. A European-wide dataset to uncover adaptive traits of Listeria monocytogenes to diverse ecological niches

Author

Félix, Benjamin, Sevellec, Yann, Palma, Federica, Douarre, Pierre Emmanuel, Felten, Arnaud, Radomski, Nicolas, Mallet, Ludovic, Blanchard, Yannick, Leroux, Aurélie, Soumet, Christophe, Bridier, Arnaud, Piveteau, Pascal, Ascensio, Eliette, Hébraud, Michel, Karpíšková, Renáta, Gelbíčová, Tereza, Torresi, Marina, Pomilio, Francesco, Cammà, Cesare, Di Pasquale, Adriano, Skjerdal, Taran, Pietzka, Ariane, Ruppitsch, Werner, Canelhas, Monica Ricão, Papić, Bojan, Hurtado, Ana, Wullings, Bart, Bulawova, Hana, Castro, Hanna, Lindström, Miia, Korkeala, Hannu, Šteingolde, Žanete, Kramarenko, Toomas, Cabanova, Lenka, Szymczak, Barbara, Gareis, Manfred, Oswaldi, Verena, Marti, Elisabet, Seyfarth, Anne-Mette, Leblanc, Jean-Charles, Guillier, Laurent, and Roussel, Sophie

Published
2022
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27. An improved assembly and annotation of the allohexaploid wheat genome identifies complete families of agronomic genes and provides genomic evidence for chromosomal translocations

Author

Clavijo, Bernardo J, Venturini, Luca, Schudoma, Christian, Accinelli, Gonzalo Garcia, Kaithakottil, Gemy, Wright, Jonathan, Borrill, Philippa, Kettleborough, George, Heavens, Darren, Chapman, Helen, Lipscombe, James, Barker, Tom, Lu, Fu-Hao, McKenzie, Neil, Raats, Dina, Ramirez-Gonzalez, Ricardo H, Coince, Aurore, Peel, Ned, Percival-Alwyn, Lawrence, Duncan, Owen, Trösch, Josua, Yu, Guotai, Bolser, Dan M, Namaati, Guy, Kerhornou, Arnaud, Spannagl, Manuel, Gundlach, Heidrun, Haberer, Georg, Davey, Robert P, Fosker, Christine, Di Palma, Federica, Phillips, Andrew L, Millar, A Harvey, Kersey, Paul J, Uauy, Cristobal, Krasileva, Ksenia V, Swarbreck, David, Bevan, Michael W, and Clark, Matthew D

Subjects
Genetics, Biotechnology, Human Genome, Algorithms, Contig Mapping, Genome, Plant, Molecular Sequence Annotation, Plant Proteins, Polymorphism, Genetic, Polyploidy, Translocation, Genetic, Triticum, Biological Sciences, Medical and Health Sciences, Bioinformatics
Abstract

Advances in genome sequencing and assembly technologies are generating many high-quality genome sequences, but assemblies of large, repeat-rich polyploid genomes, such as that of bread wheat, remain fragmented and incomplete. We have generated a new wheat whole-genome shotgun sequence assembly using a combination of optimized data types and an assembly algorithm designed to deal with large and complex genomes. The new assembly represents >78% of the genome with a scaffold N50 of 88.8 kb that has a high fidelity to the input data. Our new annotation combines strand-specific Illumina RNA-seq and Pacific Biosciences (PacBio) full-length cDNAs to identify 104,091 high-confidence protein-coding genes and 10,156 noncoding RNA genes. We confirmed three known and identified one novel genome rearrangements. Our approach enables the rapid and scalable assembly of wheat genomes, the identification of structural variants, and the definition of complete gene models, all powerful resources for trait analysis and breeding of this key global crop.

Published
2017

28. Ancient and recent hybridization in the Oreochromis cichlid fishes

Author

Ciezarek, Adam G, primary, Mehta, Tarang K, additional, Man, Angela, additional, Ford, Antonia G P, additional, Kavembe, Geraldine Dorcas, additional, Kasozi, Nasser, additional, Ngatunga, Benjamin P, additional, Shechonge, Asilatu H, additional, Tamatamah, Rashid, additional, Nyingi, Dorothy Wanja, additional, Cnaani, Avner, additional, Ndiwa, Titus C, additional, Di Palma, Federica, additional, Turner, George F, additional, Genner, Martin J, additional, and Haerty, Wilfried, additional

Published
2024
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30. Towards complete and error-free genome assemblies of all vertebrate species

Author

Rhie, Arang, McCarthy, Shane A., Fedrigo, Olivier, Damas, Joana, Formenti, Giulio, Koren, Sergey, Uliano-Silva, Marcela, Chow, William, Fungtammasan, Arkarachai, Kim, Juwan, Lee, Chul, Ko, Byung June, Chaisson, Mark, Gedman, Gregory L., Cantin, Lindsey J., Thibaud-Nissen, Francoise, Haggerty, Leanne, Bista, Iliana, Smith, Michelle, Haase, Bettina, Mountcastle, Jacquelyn, Winkler, Sylke, Paez, Sadye, Howard, Jason, Vernes, Sonja C., Lama, Tanya M., Grutzner, Frank, Warren, Wesley C., Balakrishnan, Christopher N., Burt, Dave, George, Julia M., Biegler, Matthew T., Iorns, David, Digby, Andrew, Eason, Daryl, Robertson, Bruce, Edwards, Taylor, Wilkinson, Mark, Turner, George, Meyer, Axel, Kautt, Andreas F., Franchini, Paolo, Detrich, III, H. William, Svardal, Hannes, Wagner, Maximilian, Naylor, Gavin J. P., Pippel, Martin, Malinsky, Milan, Mooney, Mark, Simbirsky, Maria, Hannigan, Brett T., Pesout, Trevor, Houck, Marlys, Misuraca, Ann, Kingan, Sarah B., Hall, Richard, Kronenberg, Zev, Sović, Ivan, Dunn, Christopher, Ning, Zemin, Hastie, Alex, Lee, Joyce, Selvaraj, Siddarth, Green, Richard E., Putnam, Nicholas H., Gut, Ivo, Ghurye, Jay, Garrison, Erik, Sims, Ying, Collins, Joanna, Pelan, Sarah, Torrance, James, Tracey, Alan, Wood, Jonathan, Dagnew, Robel E., Guan, Dengfeng, London, Sarah E., Clayton, David F., Mello, Claudio V., Friedrich, Samantha R., Lovell, Peter V., Osipova, Ekaterina, Al-Ajli, Farooq O., Secomandi, Simona, Kim, Heebal, Theofanopoulou, Constantina, Hiller, Michael, Zhou, Yang, Harris, Robert S., Makova, Kateryna D., Medvedev, Paul, Hoffman, Jinna, Masterson, Patrick, Clark, Karen, Martin, Fergal, Howe, Kevin, Flicek, Paul, Walenz, Brian P., Kwak, Woori, Clawson, Hiram, Diekhans, Mark, Nassar, Luis, Paten, Benedict, Kraus, Robert H. S., Crawford, Andrew J., Gilbert, M. Thomas P., Zhang, Guojie, Venkatesh, Byrappa, Murphy, Robert W., Koepfli, Klaus-Peter, Shapiro, Beth, Johnson, Warren E., Di Palma, Federica, Marques-Bonet, Tomas, Teeling, Emma C., Warnow, Tandy, Graves, Jennifer Marshall, Ryder, Oliver A., Haussler, David, O’Brien, Stephen J., Korlach, Jonas, Lewin, Harris A., Howe, Kerstin, Myers, Eugene W., Durbin, Richard, Phillippy, Adam M., and Jarvis, Erich D.

Published
2021
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31. The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons

Author

Braasch, Ingo, Gehrke, Andrew R, Smith, Jeramiah J, Kawasaki, Kazuhiko, Manousaki, Tereza, Pasquier, Jeremy, Amores, Angel, Desvignes, Thomas, Batzel, Peter, Catchen, Julian, Berlin, Aaron M, Campbell, Michael S, Barrell, Daniel, Martin, Kyle J, Mulley, John F, Ravi, Vydianathan, Lee, Alison P, Nakamura, Tetsuya, Chalopin, Domitille, Fan, Shaohua, Wcisel, Dustin, Cañestro, Cristian, Sydes, Jason, Beaudry, Felix EG, Sun, Yi, Hertel, Jana, Beam, Michael J, Fasold, Mario, Ishiyama, Mikio, Johnson, Jeremy, Kehr, Steffi, Lara, Marcia, Letaw, John H, Litman, Gary W, Litman, Ronda T, Mikami, Masato, Ota, Tatsuya, Saha, Nil Ratan, Williams, Louise, Stadler, Peter F, Wang, Han, Taylor, John S, Fontenot, Quenton, Ferrara, Allyse, Searle, Stephen MJ, Aken, Bronwen, Yandell, Mark, Schneider, Igor, Yoder, Jeffrey A, Volff, Jean-Nicolas, Meyer, Axel, Amemiya, Chris T, Venkatesh, Byrappa, Holland, Peter WH, Guiguen, Yann, Bobe, Julien, Shubin, Neil H, Di Palma, Federica, Alföldi, Jessica, Lindblad-Toh, Kerstin, and Postlethwait, John H

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Animals, Evolution, Molecular, Female, Fishes, Genome, Humans, Karyotype, Models, Genetic, Organ Specificity, Sequence Analysis, DNA, Transcriptome, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.

Published
2016

33. Genomic architecture and introgression shape a butterfly radiation

Author

Edelman, Nathaniel B., Frandsen, Paul B., Miyagi, Michael, Clavijo, Bernardo, Davey, John, Dikow, Rebecca B., García-Accinelli, Gonzalo, Van Belleghem, Steven M., Patterson, Nick, Neafsey, Daniel E., Challis, Richard, Kumar, Sujai, Moreira, Gilson R. P., Salazar, Camilo, Chouteau, Mathieu, Counterman, Brian A., Papa, Riccardo, Blaxter, Mark, Reed, Robert D., Dasmahapatra, Kanchon K., Kronforst, Marcus, Joron, Mathieu, Jiggins, Chris D., McMillan, W. Owen, Di Palma, Federica, Blumberg, Andrew J., Wakeley, John, Jaffe, David, and Mallet, James

Published
2019

36. Bacterial strain nomenclature in the genomic era: Life Identification Numbers using a gene-by-gene approach

Author

Palma, Federica, primary, Hennart, Melanie, additional, Jolley, Keith A., additional, Crestani, Chiara, additional, Wyres, Kelly L., additional, Bridel, Sebastien, additional, Yeats, Corin A., additional, Brancotte, Bryan, additional, Raffestin, Brice, additional, David, Sophia, additional, Lam, Margaret M. C., additional, Izdebski, Radosław, additional, Passet, Virginie, additional, Rodrigues, Carla, additional, Rethoret-Pasty, Martin, additional, Maiden, Martin C. J., additional, Aanensen, David M., additional, Holt, Kathryn E., additional, Criscuolo, Alexis, additional, and Brisse, Sylvain, additional

Published
2024
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37. A phylogenetic framework to study desirable traits in the wild relatives of Theobroma cacao (Malvaceae)

Author

Bossa‐Castro, Ana M., primary, Colli‐Silva, Matheus, additional, Pirani, José R., additional, Whitlock, Barbara A., additional, Morales Mancera, Laura T., additional, Contreras‐Ortiz, Natalia, additional, Cepeda‐Hernández, Martha L., additional, Di Palma, Federica, additional, Vives, Martha, additional, and Richardson, James E., additional

Published
2024
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38. Describing variability in pig genes involved in coronavirus infections for a One Health perspective in conservation of animal genetic resources

Author

Bovo, Samuele, Schiavo, Giuseppina, Ribani, Anisa, Utzeri, Valerio J., Taurisano, Valeria, Ballan, Mohamad, Muñoz, Maria, Alves, Estefania, Araujo, Jose P., Bozzi, Riccardo, Charneca, Rui, Di Palma, Federica, Djurkin Kušec, Ivona, Etherington, Graham, Fernandez, Ana I., García, Fabián, García-Casco, Juan, Karolyi, Danijel, Gallo, Maurizio, Martins, José Manuel, Mercat, Marie-José, Núñez, Yolanda, Quintanilla, Raquel, Radović, Čedomir, Razmaite, Violeta, Riquet, Juliette, Savić, Radomir, Škrlep, Martin, Usai, Graziano, Zimmer, Christoph, Ovilo, Cristina, and Fontanesi, Luca

Published
2021
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41. The genomic substrate for adaptive radiation in African cichlid fish.

Author

Brawand, David, Wagner, Catherine E, Li, Yang I, Malinsky, Milan, Keller, Irene, Fan, Shaohua, Simakov, Oleg, Ng, Alvin Y, Lim, Zhi Wei, Bezault, Etienne, Turner-Maier, Jason, Johnson, Jeremy, Alcazar, Rosa, Noh, Hyun Ji, Russell, Pamela, Aken, Bronwen, Alföldi, Jessica, Amemiya, Chris, Azzouzi, Naoual, Baroiller, Jean-François, Barloy-Hubler, Frederique, Berlin, Aaron, Bloomquist, Ryan, Carleton, Karen L, Conte, Matthew A, D'Cotta, Helena, Eshel, Orly, Gaffney, Leslie, Galibert, Francis, Gante, Hugo F, Gnerre, Sante, Greuter, Lucie, Guyon, Richard, Haddad, Natalie S, Haerty, Wilfried, Harris, Rayna M, Hofmann, Hans A, Hourlier, Thibaut, Hulata, Gideon, Jaffe, David B, Lara, Marcia, Lee, Alison P, MacCallum, Iain, Mwaiko, Salome, Nikaido, Masato, Nishihara, Hidenori, Ozouf-Costaz, Catherine, Penman, David J, Przybylski, Dariusz, Rakotomanga, Michaelle, Renn, Suzy CP, Ribeiro, Filipe J, Ron, Micha, Salzburger, Walter, Sanchez-Pulido, Luis, Santos, M Emilia, Searle, Steve, Sharpe, Ted, Swofford, Ross, Tan, Frederick J, Williams, Louise, Young, Sarah, Yin, Shuangye, Okada, Norihiro, Kocher, Thomas D, Miska, Eric A, Lander, Eric S, Venkatesh, Byrappa, Fernald, Russell D, Meyer, Axel, Ponting, Chris P, Streelman, J Todd, Lindblad-Toh, Kerstin, Seehausen, Ole, and Di Palma, Federica

Subjects
Animals, Cichlids, MicroRNAs, DNA Transposable Elements, Genomics, Evolution, Molecular, Phylogeny, Gene Expression Regulation, Gene Duplication, Polymorphism, Genetic, Genome, Africa, Eastern, Genetic Speciation, Lakes, Africa, Eastern, Evolution, Molecular, Polymorphism, Genetic, General Science & Technology
Abstract

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Published
2014

44. The genomic basis of adaptive evolution in threespine sticklebacks.

Author

Jones, Felicity C, Grabherr, Manfred G, Chan, Yingguang Frank, Russell, Pamela, Mauceli, Evan, Johnson, Jeremy, Swofford, Ross, Pirun, Mono, Zody, Michael C, White, Simon, Birney, Ewan, Searle, Stephen, Schmutz, Jeremy, Grimwood, Jane, Dickson, Mark C, Myers, Richard M, Miller, Craig T, Summers, Brian R, Knecht, Anne K, Brady, Shannon D, Zhang, Haili, Pollen, Alex A, Howes, Timothy, Amemiya, Chris, Broad Institute Genome Sequencing Platform & Whole Genome Assembly Team, Baldwin, Jen, Bloom, Toby, Jaffe, David B, Nicol, Robert, Wilkinson, Jane, Lander, Eric S, Di Palma, Federica, Lindblad-Toh, Kerstin, and Kingsley, David M

Subjects
Broad Institute Genome Sequencing Platform & Whole Genome Assembly Team, Chromosomes, Animals, Smegmamorpha, Sequence Analysis, DNA, Genomics, Fresh Water, Seawater, Adaptation, Physiological, Conserved Sequence, Genome, Molecular Sequence Data, Alaska, Female, Genetic Variation, Chromosome Inversion, Biological Evolution, Aquatic Organisms, Ecotype, General Science & Technology
Abstract

Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine-freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine-freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.

Published
2012

45. A high-resolution map of human evolutionary constraint using 29 mammals.

Author

Lindblad-Toh, Kerstin, Garber, Manuel, Zuk, Or, Lin, Michael F, Parker, Brian J, Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Jordan, Gregory, Mauceli, Evan, Ward, Lucas D, Lowe, Craig B, Holloway, Alisha K, Clamp, Michele, Gnerre, Sante, Alföldi, Jessica, Beal, Kathryn, Chang, Jean, Clawson, Hiram, Cuff, James, Di Palma, Federica, Fitzgerald, Stephen, Flicek, Paul, Guttman, Mitchell, Hubisz, Melissa J, Jaffe, David B, Jungreis, Irwin, Kent, W James, Kostka, Dennis, Lara, Marcia, Martins, Andre L, Massingham, Tim, Moltke, Ida, Raney, Brian J, Rasmussen, Matthew D, Robinson, Jim, Stark, Alexander, Vilella, Albert J, Wen, Jiayu, Xie, Xiaohui, Zody, Michael C, Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baldwin, Jen, Bloom, Toby, Chin, Chee Whye, Heiman, Dave, Nicol, Robert, Nusbaum, Chad, Young, Sarah, Wilkinson, Jane, Worley, Kim C, Kovar, Christie L, Muzny, Donna M, Gibbs, Richard A, Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Cree, Andrew, Dihn, Huyen H, Fowler, Gerald, Jhangiani, Shalili, Joshi, Vandita, Lee, Sandra, Lewis, Lora R, Nazareth, Lynne V, Okwuonu, Geoffrey, Santibanez, Jireh, Warren, Wesley C, Mardis, Elaine R, Weinstock, George M, Wilson, Richard K, Genome Institute at Washington University, Delehaunty, Kim, Dooling, David, Fronik, Catrina, Fulton, Lucinda, Fulton, Bob, Graves, Tina, Minx, Patrick, Sodergren, Erica, Birney, Ewan, Margulies, Elliott H, Herrero, Javier, Green, Eric D, Haussler, David, Siepel, Adam, Goldman, Nick, Pollard, Katherine S, Pedersen, Jakob S, Lander, Eric S, and Kellis, Manolis

Subjects
Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Genome Institute at Washington University, Animals, Mammals, Humans, Disease, RNA, Sequence Alignment, Sequence Analysis, DNA, Genomics, Evolution, Molecular, Phylogeny, Genome, Genome, Human, Exons, Health, Selection, Genetic, Molecular Sequence Annotation, Sequence Analysis, DNA, Evolution, Molecular, Human, Selection, Genetic, General Science & Technology
Abstract

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

Published
2011

46. A comprehensive genomic history of extinct and living elephants

Author

Palkopoulou, Eleftheria, Lipson, Mark, Mallick, Swapan, Nielsen, Svend, Rohland, Nadin, Baleka, Sina, Karpinski, Emil, Ivancevic, Atma M., To, Thu-Hien, Kortschak, R. Daniel, Raison, Joy M., Qu, Zhipeng, Chin, Tat-Jun, Alt, Kurt W., Claesson, Stefan, Dalén, Love, MacPhee, Ross D. E., Meller, Harald, Roca, Alfred L., Ryder, Oliver A., Heiman, David, Young, Sarah, Breen, Matthew, Williams, Christina, Aken, Bronwen L., Ruffier, Magali, Karlsson, Elinor, Johnson, Jeremy, Di Palma, Federica, Alfoldi, Jessica, Adelson, David L., Mailund, Thomas, Munch, Kasper, Lindblad-Toh, Kerstin, Hofreiter, Michael, Poinar, Hendrik, and Reich, David

Published
2018

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