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Article ; Online: The value of hybrid genomes: Building two highly contiguous reference genome assemblies to advance Canis genomic studies.

Bredemeyer, Kevin R / vonHoldt, Bridgett M / Foley, Nicole M / Childers, Isabella / Brzeski, Kristin E / Murphy, William J

The Journal of heredity

2024

Abstract: Previous studies of canid population and evolutionary genetics have relied on high-quality domestic dog reference genomes that have been produced primarily for biomedical and trait mapping studies in dog breeds. However, the absence of highly contiguous ... ...

Abstract	Previous studies of canid population and evolutionary genetics have relied on high-quality domestic dog reference genomes that have been produced primarily for biomedical and trait mapping studies in dog breeds. However, the absence of highly contiguous genomes from other Canis species like the gray wolf and coyote, that represent additional distinct demographic histories, may bias inferences regarding inter-specific genetic diversity and phylogenetic relationships. Here, we present single haplotype de novo genome assemblies for the gray wolf and coyote, generated by applying the trio-binning approach to long sequence reads generated from the genome of a female first-generation hybrid produced from a gray wolf and coyote mating. The assemblies were highly contiguous, with contig N50 sizes of 44.6 Mb and 42.0 Mb for the wolf and coyote, respectively. Genome scaffolding and alignments between the two Canis assemblies and published dog reference genomes showed near complete collinearity, with one exception: a coyote-specific chromosome fission of chromosome 13 and fusion of the proximal portion of that chromosome with chromosome 8, retaining the Canis-typical haploid chromosome number of 2n=78. We evaluated mapping quality for previous RAD-seq data from 334 canids and found nearly identical mapping quality and patterns among canid species and regional populations regardless of the genome used for alignment (dog, coyote, or gray wolf). These novel wolf and coyote genome reference assemblies will be important resources for proper and accurate inference of Canis demography, taxonomic evaluation, and conservation genetics.
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3044-2
ISSN	1465-7333 ; 0022-1503
ISSN (online)	1465-7333
ISSN	0022-1503
DOI	10.1093/jhered/esae013
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Article ; Online: Karyotypic stasis and swarming influenced the evolution of viral tolerance in a species-rich bat radiation.

Foley, Nicole M / Harris, Andrew J / Bredemeyer, Kevin R / Ruedi, Manuel / Puechmaille, Sebastien J / Teeling, Emma C / Criscitiello, Michael F / Murphy, William J

Cell genomics

2024 Volume 4, Issue 2, Page(s) 100482

Abstract: The emergence of COVID-19 and severe acute respiratory syndrome (SARS) has prioritized understanding bats' viral tolerance. Myotis bats are exceptionally species rich and have evolved viral tolerance. They also exhibit swarming, a cryptic behavior where ... ...

Abstract	The emergence of COVID-19 and severe acute respiratory syndrome (SARS) has prioritized understanding bats' viral tolerance. Myotis bats are exceptionally species rich and have evolved viral tolerance. They also exhibit swarming, a cryptic behavior where large, multi-species assemblages gather for mating, which has been hypothesized to promote interspecific hybridization. To resolve the coevolution of genome architecture and their unusual antiviral tolerance, we undertook a phylogenomic analysis of 60 Old World Myotis genomes. We demonstrate an extensive history of introgressive hybridization that has replaced the species phylogeny across 17%-93% of the genome except for pericentromeric regions of macrochromosomes. Introgression tracts were enriched on microchromosome regions containing key antiviral pathway genes overexpressed during viral challenge experiments. Together, these results suggest that the unusual Myotis karyotype may have evolved to selectively position immune-related genes in high recombining genomic regions prone to introgression of divergent alleles, including a diversity of interleukin loci responsible for the release of pro-inflammatory cytokines.
MeSH term(s)	Animals ; Chiroptera/genetics ; Genome ; Genomics ; Karyotype ; Antiviral Agents
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article
ISSN	2666-979X
ISSN (online)	2666-979X
DOI	10.1016/j.xgen.2023.100482
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Article ; Online: Genomic architecture constrained placental mammal X Chromosome evolution.

Brashear, Wesley A / Bredemeyer, Kevin R / Murphy, William J

Genome research

2021 Volume 31, Issue 8, Page(s) 1353–1365

Abstract: Susumu Ohno proposed that the gene content of the mammalian X Chromosome should remain highly conserved due to dosage compensation. X Chromosome linkage (gene order) conservation is widespread in placental mammals but does not fall within the scope of ... ...

Abstract	Susumu Ohno proposed that the gene content of the mammalian X Chromosome should remain highly conserved due to dosage compensation. X Chromosome linkage (gene order) conservation is widespread in placental mammals but does not fall within the scope of Ohno's prediction and may be an indirect result of selection on gene content or selection against rearrangements that might disrupt X-Chromosome inactivation (XCI). Previous comparisons between the human and mouse X Chromosome sequences have suggested that although single-copy X Chromosome genes are conserved between species, most ampliconic genes were independently acquired. To better understand the evolutionary and functional constraints on X-linked gene content and linkage conservation in placental mammals, we aligned a new, high-quality, long-read X Chromosome reference assembly from the domestic cat (incorporating 19.3 Mb of targeted BAC clone sequence) to the pig, human, and mouse assemblies. A comprehensive analysis of annotated X-linked orthologs in public databases demonstrated that the majority of ampliconic gene families were present on the ancestral placental X Chromosome. We generated a domestic cat Hi-C contact map from an F1 domestic cat/Asian leopard cat hybrid and demonstrated the formation of the bipartite structure found in primate and rodent inactivated X Chromosomes. Conservation of gene order and recombination patterns is attributable to strong selective constraints on three-dimensional genomic architecture necessary for superloop formation. Species with rearranged X Chromosomes retain the ancestral order and relative spacing of loci critical for superloop formation during XCI, with compensatory inversions evolving to maintain these long-range physical interactions.
MeSH term(s)	Animals ; Cats/genetics ; Eutheria/genetics ; Evolution, Molecular ; Female ; Genomics ; Mice ; Placenta ; Pregnancy ; Swine ; X Chromosome/genetics ; X Chromosome Inactivation
Language	English
Publishing date	2021-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.275274.121
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Zs.A 3729: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Phylogenomics and the Genetic Architecture of the Placental Mammal Radiation.

Murphy, William J / Foley, Nicole M / Bredemeyer, Kevin R / Gatesy, John / Springer, Mark S

Annual review of animal biosciences

2020 Volume 9, Page(s) 29–53

Abstract: The genomes of placental mammals are being sequenced at an unprecedented rate. Alignments of hundreds, and one day thousands, of genomes spanning the rich living and extinct diversity of species offer unparalleled power to resolve phylogenetic ... ...

Abstract	The genomes of placental mammals are being sequenced at an unprecedented rate. Alignments of hundreds, and one day thousands, of genomes spanning the rich living and extinct diversity of species offer unparalleled power to resolve phylogenetic controversies, identify genomic innovations of adaptation, and dissect the genetic architecture of reproductive isolation. We highlight outstanding questions about the earliest phases of placental mammal diversification and the promise of newer methods, as well as remaining challenges, toward using whole genome data to resolve placental mammal phylogeny. The next phase of mammalian comparative genomics will see the completion and application of finished-quality, gapless genome assemblies from many ordinal lineages and closely related species. Interspecific comparisons between the most hypervariable genomic loci will likely reveal large, but heretofore mostly underappreciated, effects on population divergence, morphological innovation, and the origin of new species.
MeSH term(s)	Adaptation, Biological ; Animals ; Biological Evolution ; Eutheria/classification ; Eutheria/genetics ; Genetic Speciation ; Genomics ; Phylogeny
Language	English
Publishing date	2020-11-23
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2700164-7
ISSN	2165-8110 ; 2165-8102
ISSN (online)	2165-8110
ISSN	2165-8102
DOI	10.1146/annurev-animal-061220-023149
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Article ; Online: A genomic timescale for placental mammal evolution.

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

Science (New York, N.Y.)

2023 Volume 380, Issue 6643, Page(s) eabl8189

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, ... ...

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.
MeSH term(s)	Animals ; Female ; Biological Evolution ; Eutheria/classification ; Eutheria/genetics ; Evolution, Molecular ; Fossils ; Genomics/methods ; Phylogeny ; Genetic Variation ; Time Factors
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abl8189
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Rapid Macrosatellite Evolution Promotes X-Linked Hybrid Male Sterility in a Feline Interspecies Cross.

Bredemeyer, Kevin R / Seabury, Christopher M / Stickney, Mark J / McCarrey, John R / vonHoldt, Bridgett M / Murphy, William J

Molecular biology and evolution

2021 Volume 38, Issue 12, Page(s) 5588–5609

Abstract: The sterility or inviability of hybrid offspring produced from an interspecific mating result from incompatibilities between parental genotypes that are thought to result from divergence of loci involved in epistatic interactions. However, attributes ... ...

Abstract	The sterility or inviability of hybrid offspring produced from an interspecific mating result from incompatibilities between parental genotypes that are thought to result from divergence of loci involved in epistatic interactions. However, attributes contributing to the rapid evolution of these regions also complicates their assembly, thus discovery of candidate hybrid sterility loci is difficult and has been restricted to a small number of model systems. Here we reported rapid interspecific divergence at the DXZ4 macrosatellite locus in an interspecific cross between two closely related mammalian species: the domestic cat (Felis silvestris catus) and the Jungle cat (Felis chaus). DXZ4 is an interesting candidate due to its structural complexity, copy number variability, and described role in the critical yet complex biological process of X-chromosome inactivation. However, the full structure of DXZ4 was absent or incomplete in nearly every available mammalian genome assembly given its repetitive complexity. We compared highly continuous genomes for three cat species, each containing a complete DXZ4 locus, and discovered that the felid DXZ4 locus differs substantially from the human ortholog, and that it varies in copy number between cat species. Additionally, we reported expression, methylation, and structural conformation profiles of DXZ4 and the X chromosome during stages of spermatogenesis that have been previously associated with hybrid male sterility. Collectively, these findings suggest a new role for DXZ4 in male meiosis and a mechanism for feline interspecific incompatibility through rapid satellite divergence.
MeSH term(s)	Animals ; Cats/genetics ; Felidae/genetics ; Genome ; Infertility, Male/genetics ; Male ; X Chromosome/genetics ; X Chromosome Inactivation
Language	English
Publishing date	2021-09-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msab274
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Article ; Online: An ASO therapy for Angelman syndrome that targets an evolutionarily conserved region at the start of the

Dindot, Scott V / Christian, Sarah / Murphy, William J / Berent, Allyson / Panagoulias, Jennifer / Schlafer, Annalise / Ballard, Johnathan / Radeva, Kamelia / Robinson, Ruth / Myers, Luke / Jepp, Thomas / Shaheen, Hillary / Hillman, Paul / Konganti, Kranti / Hillhouse, Andrew / Bredemeyer, Kevin R / Black, Lauren / Douville, Julie

Science translational medicine

2023 Volume 15, Issue 688, Page(s) eabf4077

Abstract: Angelman syndrome is a devastating neurogenetic disorder for which there is currently no effective treatment. It is caused by mutations or epimutations affecting the expression or function of the maternally inherited allele of the ubiquitin-protein ... ...

Abstract	Angelman syndrome is a devastating neurogenetic disorder for which there is currently no effective treatment. It is caused by mutations or epimutations affecting the expression or function of the maternally inherited allele of the ubiquitin-protein ligase E3A (
MeSH term(s)	Humans ; Angelman Syndrome/therapy ; Angelman Syndrome/drug therapy ; Alleles ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Ubiquitin-Protein Ligases (EC 2.3.2.27) ; UBE3A protein, human (EC 2.3.2.26)
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abf4077
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Article ; Online: Single-haplotype comparative genomics provides insights into lineage-specific structural variation during cat evolution.

Bredemeyer, Kevin R / Hillier, LaDeana / Harris, Andrew J / Hughes, Graham M / Foley, Nicole M / Lawless, Colleen / Carroll, Rachel A / Storer, Jessica M / Batzer, Mark A / Rice, Edward S / Davis, Brian W / Raudsepp, Terje / O'Brien, Stephen J / Lyons, Leslie A / Warren, Wesley C / Murphy, William J

Nature genetics

2023 Volume 55, Issue 11, Page(s) 1953–1963

Abstract: The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes ... ...

Abstract	The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discerned that cat genomes have a paucity of segmental duplications relative to great apes, explaining their remarkable karyotypic stability. X chromosomes were hotspots of structural variation, including enrichment with inversions in a large recombination desert with characteristics of a supergene. The X-linked macrosatellite DXZ4 evolves more rapidly than 99.5% of the genome clarifying its role in felid hybrid incompatibility. Resolved sensory gene repertoires revealed functional copy number changes associated with ecomorphological adaptations, sociality and domestication. This study highlights the value of gapless genomes to reveal structural mechanisms underpinning karyotypic evolution, reproductive isolation and ecological niche adaptation.
MeSH term(s)	Haplotypes/genetics ; Evolution, Molecular ; Genomics ; Genome/genetics ; Gene Dosage
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-023-01548-y
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Ultracontinuous Single Haplotype Genome Assemblies for the Domestic Cat (Felis catus) and Asian Leopard Cat (Prionailurus bengalensis).

Bredemeyer, Kevin R / Harris, Andrew J / Li, Gang / Zhao, Le / Foley, Nicole M / Roelke-Parker, Melody / O'Brien, Stephen J / Lyons, Leslie A / Warren, Wesley C / Murphy, William J

The Journal of heredity

2020 Volume 112, Issue 2, Page(s) 165–173

Abstract: In addition to including one of the most popular companion animals, species from the cat family Felidae serve as a powerful system for genetic analysis of inherited and infectious disease, as well as for the study of phenotypic evolution and speciation. ... ...

Abstract	In addition to including one of the most popular companion animals, species from the cat family Felidae serve as a powerful system for genetic analysis of inherited and infectious disease, as well as for the study of phenotypic evolution and speciation. Previous diploid-based genome assemblies for the domestic cat have served as the primary reference for genomic studies within the cat family. However, these versions suffered from poor resolution of complex and highly repetitive regions, with substantial amounts of unplaced sequence that is polymorphic or copy number variable. We sequenced the genome of a female F1 Bengal hybrid cat, the offspring of a domestic cat (Felis catus) x Asian leopard cat (Prionailurus bengalensis) cross, with PacBio long sequence reads and used Illumina sequence reads from the parents to phase >99.9% of the reads into the 2 species' haplotypes. De novo assembly of the phased reads produced highly continuous haploid genome assemblies for the domestic cat and Asian leopard cat, with contig N50 statistics exceeding 83 Mb for both genomes. Whole-genome alignments reveal the Felis and Prionailurus genomes are colinear, and the cytogenetic differences between the homologous F1 and E4 chromosomes represent a case of centromere repositioning in the absence of a chromosomal inversion. Both assemblies offer significant improvements over the previous domestic cat reference genome, with a 100% increase in contiguity and the capture of the vast majority of chromosome arms in 1 or 2 large contigs. We further demonstrated that comparably accurate F1 haplotype phasing can be achieved with members of the same species when one or both parents of the trio are not available. These novel genome resources will empower studies of feline precision medicine, adaptation, and speciation.
MeSH term(s)	Animals ; Cats/genetics ; Chromosome Mapping ; Felidae/genetics ; Female ; Genome ; Haplotypes ; Hybridization, Genetic ; Male
Language	English
Publishing date	2020-11-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3044-2
ISSN	1465-7333 ; 0022-1503
ISSN (online)	1465-7333
ISSN	0022-1503
DOI	10.1093/jhered/esaa057
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Article ; Online: Vocal learning-associated convergent evolution in mammalian proteins and regulatory elements.

Wirthlin, Morgan E / Schmid, Tobias A / Elie, Julie E / Zhang, Xiaomeng / Kowalczyk, Amanda / Redlich, Ruby / Shvareva, Varvara A / Rakuljic, Ashley / Ji, Maria B / Bhat, Ninad S / Kaplow, Irene M / Schäffer, Daniel E / Lawler, Alyssa J / Wang, Andrew Z / Phan, BaDoi N / Annaldasula, Siddharth / Brown, Ashley R / Lu, Tianyu / Lim, Byung Kook /

Azim, Eiman / Clark, Nathan L / Meyer, Wynn K / Pond, Sergei L Kosakovsky / Chikina, Maria / Yartsev, Michael M / 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 / 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 / Karlsson, Elinor K / Keough, Kathleen C / Kirilenko, Bogdan / Koepfli, Klaus-Peter / Korstian, Jennifer M / Kozyrev, Sergey V / Lawless, Colleen / Lehmann, Thomas / Levesque, Danielle L / Lewin, Harris A / Li, Xue / Lind, Abigail / Lindblad-Toh, Kerstin / Mackay-Smith, Ava / Marinescu, Voichita D / Marques-Bonet, Tomas / Mason, Victor C / Meadows, Jennifer R S / 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 F A / Springer, Mark / Srinivasan, Chaitanya / Steiner, Cynthia / Storer, Jessica M / Sullivan, Kevin A M / Sullivan, Patrick F / Sundström, Elisabeth / Supple, Megan A / Swofford, Ross / Talbot, Joy-El / Teeling, Emma / Turner-Maier, Jason / Valenzuela, Alejandro / Wagner, Franziska / Wallerman, Ola / Wang, Chao / Wang, Juehan / Weng, Zhiping / Wilder, Aryn P / Xue, James R

Science (New York, N.Y.)

2024 Volume 383, Issue 6690, Page(s) eabn3263

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 ... ...

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 (
MeSH term(s)	Animals ; Chiroptera/genetics ; Chiroptera/physiology ; Vocalization, Animal/physiology ; Motor Cortex/cytology ; Motor Cortex/physiology ; Chromatin/metabolism ; Enhancer Elements, Genetic ; Motor Neurons/physiology ; Larynx/physiology ; Epigenesis, Genetic ; Genome ; Gene Expression Regulation ; Evolution, Molecular ; Proteins/genetics ; Proteins/metabolism ; Amino Acid Sequence ; Eutheria/genetics ; Eutheria/physiology ; Machine Learning
Chemical Substances	Chromatin ; Proteins
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abn3263
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