Journal Cover Publications
placement in complete listing of publications by the Batzer lab; the ^ denotes equal authorship.
All of these journal cover illustrations associated with the Batzer Lab can be downloaded
from Journal Covers – 17; to view larger images on this page, click covers.
_2023-2002.jpg)
2023
302
Bredemeyer^ and Hillier^ et al. 2023
Single-haplotype comparative genomics provides insights into lineage-specific structural variation during cat evolution. Nature Genetics 55:1953-1963.
Full Citation:
Bredemeyer^, K. R., L. Hillier^, A. J. Harris, G. M. Hughes, N. M. Foley, C. Lawless, R. A. Carroll, J. M. Storer, M. A. Batzer, E. S. Rice, B. W. Davis, T. Raudsepp, S. J. O’Brien, L. A. Lyons, W. C. Warren, and W. J. Murphy 2023
Single-haplotype comparative genomics provides insights into lineage-specific structural variation during cat evolution. Nature Genetics 55:1953-1963.
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 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.
Supplemental Data:
Nature_Genetics_Reporting_Summary.pdf
Supplementary_Data_pending.pdf
300
Sorensen^, Harris^, Zhang^ and Raveendran^ et al. 2023
Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons. Science 380:eabn8153 [primate genomes special issue].
Full Citation:
Sorensen, E. F., R. A. Harris, L. Zhang, M. Raveendran, L. F. K. Kuderna, J. A. Walker, J. M. Storer, M. Kuhlwilm, C. Fontsere, L, Seshadri, C. M. Bergey, A. S. Burrell, J. Bergmann, J. E. Phillips-Conroy, F. Shiferaw, K. L. Chiou, I. S. Chuma, J. D. Keyyu, J. Fischer, M.-C. Gingras, S. Salvi, H. Doddapaneni, M. H. Schierup, M. A. Batzer, C. J. Jolly, S. Knauf, D. Zinner, K. K.-H. Farh, T. Marques-Bonet, K. Munch, C. Roos, and J. Rogers 2023
Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons. Science 380:eabn8153 [primate genomes special issue].
Abstract:
Baboons (genus Papio) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high-coverage whole-genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and interspecies gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes.
Supplemental Data:
FigS1_L1_Structure_K2toK10plot.docx
FigS1_L1_Structure_K2toK10plot.pdf
Papio_L1_Structure_K2toK10_20_Dec_2021.xlsx
2015
278
The 1000 Genomes Project Consortium 2015
A global reference for human genetic variation. Nature 526:68-74.
Full Citation:
The 1000 Genomes Project Consortium. 2015
A global reference for human genetic variation. Nature 526:68-74.
Abstract:
The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combina- tion of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes .99% of SNP variants with a frequency of .1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
Supplemental Data:
None.
277
Sudmant^, Rausch^, Gardner^, R. E. Handsaker^, Abyzov^, Huddleston^, Zhang^, and Ye^ et al. 2015
An integrated map of structural variation in 2,504 human genomes. Nature 526:75-81.
Full Citation:
Sudmant^, P. H., T. Rausch^, E. J. Gardner^, R. E. Handsaker^, A. Abyzov^, J. Huddleston^, Y. Zhang^, K. Ye^, G. Jun, M. H.-Y. Fritz, M. K. Konkel, A. Malhotra, A. M. Stuetz, X. Shi, F. P. Casale, J. Chen, F. Hormozdiari, G. Dayama, K. Chen, M. Malig, M. J. P. Chaisson, K. Walter, S. Meiers, S. Kashin, E. Garrison, C. Alkan, D. Antaki, T. Bae, P. Chines, Z. Chong, L. Clarke, E. Dal, L. Ding, S. Emery, X. Fan, M. Gujral, F. Kahveci, J. M. Kidd, H. Y. K. Lam, S. McCarthy, P. Flicek, R. A. Gibbs, G. Marth, A. Menelaou, X. J. Mu, D. M. Muzny, B. Nelson, A. Noor, N. F. Parrish, A. Quitadamo, B. Raeder, E. Schadt, A. Schlattl, A. Shabalin, A. Untergasser, E.-W. Lameijer, J. A. Walker, M. Wang, F. Yu, C. Zhang, J. Zhang, X. Zheng-Bradley, W. Zhou, T. Zichner, J. Sebat, M. A. Batzer, S. A. McCarroll, The 1000 Genomes Project Consortium, R. E. Mills, M. B. Gerstein, A. Bashir, O. Stegle, S. E. Devine, C. Lee, E. E. Eichler, and J. O. Korbel. 2015
An integrated map of structural variation in 2,504 human genomes. Nature 526:75-81.
Abstract:
Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.
Supplemental Data:
Supplementary Data.xlsx
2014
273
Carbone et al. 2014
Gibbon genome and the fast karyotype evolution of small apes. Nature 513:195-201.
Full Citation:
Carbone, L., R. A. Harris, S. Gnerre, K. R. Veeramah, B. Lorente-Galdos, J. Huddleston, T. J. Meyer, J. Herrero, C. Roos, B. Aken, F. Anaclerio, N. Archidiacono, C. Baker, D. Barrell, M. A. Batzer, K. Beal, A. Blancher, C. L. Bohrson, M. Brameier, M. S. Campbell, O. Capozzi, C. Casola, G. Chiatante, A. Cree, A. Damert, P. J. de Jong, L. Dumas, M. Fern, ez-Callejo, P. Flicek, N. V. Fuchs, I. Gut, M. Gut, M. W. Hahn, J. Hernández-Rodríguez, L. W. Hillier, R. Hubley, B. Ianc, Z. Izsvák, N. G. Jablonski, L. M. Johnstone, A. Karimpour-Fard, M. K. Konkel, D. Kostka, N. H. Lazar, S. L. Lee, L. R. Lewis, Y. Liu, D. P. Locke, S. Mallick, F. L. Mendez, M. Muffato, L. V. Nazareth, K. A. Nevonen, M. O'Bleness, C. Ochis, D. T. Odom, K. S. Pollard, J. Quilez, D. Reich, M. Rocchi, G. G. Schumann, S. Searle, J. M. Sikela, G. Skollar, A. Smit, K. Sonmez, B. ten Hallers, E. Terhune, G. W. C. Thomas, B. Ullmer, M. Ventura, J. A. Walker, J. D. Wall, L. Walter, M. C. Ward, S. J. Wheelan, C. W. Whelan, S. White, L. J. Wilhelm, A. E. Woerner, M. Yandell, B. Zhu, M. F. Hammer, T. Marques-Bonet, E. E. Eichler, L. Fulton, C. Fronick, D. M. Muzny, W. C. Warren, K. C. Worley, J. Rogers, R. K. Wilson, and R. A. Gibbs. 2014
Gibbon genome and the fast karyotype evolution of small apes. Nature 513:195-201.
Abstract:
Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys and great apes. Here we present the assembly and analysis of a northern white-cheeked gibbon (Nomascus leucogenys) genome. We describe the propensity for a gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We further show that the gibbon genera (Nomascus, Hylobates, Hoolock and Symphalangus) experienced a near-instantaneous radiation ~ 5 million years ago, coincident with major geographical changes in southeast Asia that caused cycles of habitat compression and expansion. Finally, we identify signatures of positive selection in genes important for forelimb development (TBX5) and connective tissues (COL1A1) that may have been involved in the adaptation of gibbons to their arboreal habitat.
Supplemental Data:
Extended Data Figure 1.tif
Extended Data Figure 2.tif
Extended Data Figure 3.tif
Extended Data Figure 4.tif
Extended Data Figure 5.tif
Extended Data Figure 6.tif
Extended Data Table 1.tif
Nature Supplementary Information.pdf
Nature Supplemental Data 1.xlsx
Nature Supplemental Data 2.xlsx
Nature Supplemental Data 3.pdf
Nature Supplemental Data 4.xlsx
Nature Supplemental Data 5.xlsx
Nature Supplemental Data 6.pptx
Nature Supplemental Data 7.xlsx
Nature Supplemental Data 8.xlsx
Nature Supplemental Data 9.pdf
2012
259
Carbone et al. 2012
Centromere remodeling in Hoolock leuconedys (Hylobatidae) uncovers a new transposable element unique to the gibbons. Genome Biology and Evolution 4:648-658.
Full Citation:
Carbone, L., R. A. Harris, A. R. Mootnick, A. Milosavljevic, D. I. K. Martin, M. Rocchi, O. Capozzi, N. Archidiacono, M. K. Konkel, J. A. Walker, M. A. Batzer, and P. J. de Jong. 2012
Centromere remodeling in Hoolock leuconedys (Hylobatidae) uncovers a new transposable element unique to the gibbons. Genome Biology and Evolution 4:648-658.
Abstract:
Gibbons (Hylobatidae) shared a common ancestor with the other hominoids only 15-18 million years ago. Nevertheless, gibbons show very distinctive features that include heavily rearranged chromosomes. Previous observations indicate that this phenomenon may be linked to the attenuated epigenetic repression of transposable elements (TEs) in gibbon species. Here we describe the massive expansion of a repeat in almost all the centromeres of the eastern hoolock gibbon (Hoolock leuconedys). We discovered that this repeat is a new composite TE originating from the combination of portions of three other elements (L1ME5, AluSz6, and SVA_A) and thus named it LAVA. We determined that this repeat is found in all the gibbons but does not occur in other hominoids. Detailed investigation of 46 different LAVA elements revealed that the majority of them have target site duplications (TSDs) and a poly-A tail, suggesting that they have been retrotransposing in the gibbon genome. Although we did not find a direct correlation between the emergence of LAVA elements and human-gibbon synteny breakpoints, this new composite transposable element is another mark of the great plasticity of the gibbon genome. Moreover, the centromeric expansion of LAVA insertions in the hoolock closely resembles the massive centromeric expansion of the KERV-1 retroelement reported for wallaby (marsupial) interspecific hybrids. The similarity between the two phenomena is consistent with the hypothesis that evolution of the gibbons is characterized by defects in epigenetic repression of TEs, perhaps triggered by interspecific hybridization.
Supplemental Data:
Supplementary Figure 1.jpg
Supplementary Figure 2.jpg
Supplementary Figure 3.pptx
Supplementary Figure 4.jpg
Supplementary File - LAVA Consensus Sequence.docx
Supplementary Tables S1 and S2, Supplementary Table S3 Legend, and Supplementary Figure Legends.docx
Supplementary Table S3.pdf
2011
245
Locke et al. 2011
Comparative and demographic analysis of orang-utan genomes. Nature 469:529-533.
Full Citation:
Locke, D. P., L. W. Hillier, W. C. Warren, K. C. Worley, L. V. Nazareth, D. M. Muzny, S.-P. Yang, Z. Wang, A. T. Chinwalla, P. Minx, M. Mitreva, L. Cook, K. D. Delehaunty, C. Fronick, H. Schmidt, L. A. Fulton, R. S. Fulton, J. O. Nelson, V. Magrini, C. Pohl, T. A. Graves, C. Markovic, A. Cree, H. H. Dinh, J. Hume, C. L. Kovar, G. R. Fowler, G. Lunter, S. Meader, A. Heger, C. P. Ponting, T. Marques-Bonet, C. Alkan, L. Chen, Z. Cheng, J. M. Kidd, E. E. Eichler, S. White, S. Searle, A. J. Vilella, Y. Chen, P. Flicek, J. Ma, B. Raney, B. Suh, R. Burhans, J. Herrero, D. Haussler, R. Faria, O. Fernando, F. Darré, D. Farré, E. Gazave, M. Oliva, A. Navarro, R. Roberto, O. Capozzi, N. Archidiacono, G. Della Valle, S. Purgato, M. Rocchi, M. K. Konkel, J. A. Walker, B. Ullmer, M. A. Batzer, A. F. A. Smit, R. Hubley, C. Casola, D. R. Schrider, M. W. Hahn, V. Quesada, X. S. Puente, G. R. Ordoñez, C. López-Otín, T. Vinar, B. Brejova, A. Ratan, R. S. Harris, W. Miller, C. Kosiol, H. A. Lawson, V. Taliwal, A. L. Martins, A. Siepel, A. RoyChoudhury, X. Ma, J. Degenhardt, C. D. Bustamante, R. N. Gutenkunst, T. Mailund, J. Y. Dutheil, A. Hobolth, M. H. Schierup, O. A. Ryder, Y. Yoshinaga, P. J. de Jong, G. M. Weinstock, J. Rogers, E. R. Mardis, R. A. Gibbs, and R. K. Wilson. 2011
Comparative and demographic analysis of orang-utan genomes. Nature 469:529-533.
Abstract:
'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 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, 400,000 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.
Supplemental Data:
Retrotransposon Loci Primers and Conditions.xls
Nature Supplemental Information.pdf
Nature Supplemental Data 1.xls
Nature Supplemental Data 2.xls
Nature Supplemental Data 3.xls
Nature Supplemental Data 4.xls
Nature Supplemental Data 5.xls
Nature Supplemental Data 6.xls
Nature Supplemental Data 7.xls
2010
241
The 1000 Genomes Project Consortium 2010
A map of human genome variation from population scale sequencing. Nature 467:1061-1073.
Full Citation:
The 1000 Genomes Project Consortium. 2010
A map of human genome variation from population scale sequencing. Nature 467:1061-1073.
Abstract:
The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 1028 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.
Supplemental Data:
None.
2009
218
Srikanta et al. 2009
An alternative pathway for Alu retrotransposition suggests a role in DNA double-strand break repair. Genomics 93:205-212.
Full Citation:
2009
An alternative pathway for Alu retrotransposition suggests a role in DNA double-strand break repair. Genomics 93:205-212.
Abstract:
The Alu family is a highly successful group of non-LTR retrotransposons ubiquitously found in primate genomes. Similar to the L1 retrotransposon family, Alu elements integrate primarily through an endonuclease-dependent mechanism termed target site-primed reverse transcription (TPRT). Recent studies have suggested that, in addition to TPRT, L1 elements occasionally utilize an alternative endonucleaseindependent pathway for genomic integration. To determine whether an analogous mechanism exists for Alu elements, we have analyzed three publicly available primate genomes (human, chimpanzee and rhesus macaque) for endonuclease-independent recently integrated or lineage specific Alu insertions. We recovered twenty-three examples of such insertions and show that these insertions are recognizably different from classical TPRT-mediated Alu element integration. We suggest a role for this process in DNA double-strand break repair and present evidence to suggest its association with intra-chromosomal translocations, in-vitro RNA recombination (IVRR), and synthesis-dependent strand annealing (SDSA).
Supplemental Data:
Supplemental Primers.xls
Supplemental Sequences.rar
2008
209
Warren et al. 2008
Genome analysis of the platypus reveals unique signatures of evolution. Nature 452:175-183.
Full Citation:
Warren, W. C., L. W. Hillier, J. A. Marshall Graves, E. Birney, C. P. Ponting, F. Grützner, K. Belov, W. Miller, L. Clarke, A. T. Chinwalla, S.-P. Yang, A. Heger, D. Locke, P. Miethke, P. D. Waters, F. Veyrunes, L. Fulton, B. Fulton, T. Graves, J. Wallis, X. S. Puente, C. López-Otín, G. R. Ordóñez, E. E. Eichler, L. Chen, Z. Cheng, J. E. Deakin, A. Alsop, K. Thompson, P. Kirby, A. T. Papenfuss, M. J. Wakefield, T. Olender, D. Lancet, G. A. Huttley, A. F. A. Smit, A. Pask, P. Temple-Smith, M. A. Batzer, J. A. Walker, M. K. Konkel, R. S. Harris, C. M. Whittington, E. S. W. Wong, N. Gemmell, E. Buschiazzo, I. V. Jentzsch, A. Merkel, J. Schmitz, A. Zemann, G. Churakov, J. O. Kriegs, J. Brosius, E. Murchison, R. Sachidan, am, C. Smith, A. Stark, P. Kheradpour, G. Hannon, E. Tsend-Ayush, D. McMillan, R. Attenborough, W. Rens, M. Ferguson-Smith, C. M. Lefèvre, J. A. Sharp, K. R. Nicholas, D. A. Ray, M. Kube, R. Reinhard, T. H. Pringle, J. Taylor, R. C. Jones, B. Nixon, J.-L. Dacheux, H. Niwa, Y. Sekita, X. Huang, P. Flicek, C. Webber, R. Hardison, J. Nelson, K. Hallsworth-Pepin, K. Delehaunty, C. Markovic. P. Minx, Y. Feng, C. Kremitzki, M. Mitreva, J. Glasscock, T. Whylie, P. Wohldmann, P. Thiru, M. Nahn, C. Pol, S. M. Smith, S. Hou, M. Nefedov, P. J. de Jong, M. B. Renfree, E. R. Mardis, and R. K. Wilson. 2008
Genome analysis of the platypus reveals unique signatures of evolution. Nature 452:175-183.
Abstract:
We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venomsimilar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.
Supplemental Data:
Discover Magazine, 100 Top Science Stories of 2008.pdf
Table R1: Loci, PCR Primers, Positions.xls
Table R2: Polymorphic Genotypes.xls
Table R3: Population Allele Frequencies.xls
Table R4: Insertion Polymorphisms.xls
Supplementary Information.pdf
Supplementary Tables.pdf
Supplementary Figures.pdf
Supplementary Data: Primers.xls
Supplementary Data: Accession Codes.pdf
Supplementary Data: Sample ID List.xlsx
2007
195
Mikkelsen et al. 2007
Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. Nature 447:167-178.
Full Citation:
Mikkelsen, T. S., M. J. Wakefield, B. Aken, C. T. Amemiya, J. L. Chang, S. Duke, M. Garber, A. J. Gentles, L. Goodstadt, A. Heger, J. Jurka, M. Kamal, E. Mauceli, S. M. J. Searle, T. Sharpe, M. L. Baker, M. A. Batzer, P. V. Benos, K. Belov, M. Clamp, A. Cook, J. Cuff, R. Das, L. Davidow, J. E. Deakin, M. J. Fazzari, J. L. Glass, M. Grabherr, J. M. Greally, W. Gu, T. A. Hore, G. A. Huttley, R. L. Jirtle, E. Koina, J. T. Lee, S. Mahony, M. A. Marra, R. D. Miller, R. D. Nicholls, M. Oda, A. T. Papenfuss, Z. E. Parra, D. D. Pollock, D. A. Ray, J. E. Schein, T. P. Speed, K. Thompson, J. L. VandeBerg, C. M. Wade, J. A. Walker, P. D. Waters, C. Webber, J. R. Weidman, X. Xie, M. C. Zody, Broad Institute Genome Sequencing Platform, Broad Institute Whole Genome Assembly Team, J. A. Marshall Graves, C. P. Ponting, M. Breen, P. B. Samollow, E. S. Lander, and K. Lindblad-Toh. 2007
Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. Nature 447:167-178.
Abstract:
We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As thefirst metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization andevolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theoriesabout genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequencecomposition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison ofopossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding andnon-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specificdifferences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. Incontrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergenceof Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted bytransposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
Supplemental Data:
Supplemental Data.pdf
194
Han et al. 2007
Mobile DNA in Old World monkeys: a glimpse through the rhesus macaque genome. Science 316:238-240.
Full Citation:
Han, K., M. K. Konkel, J. Xing, H. Wang, J. Lee, T. J. Meyer, C. T. Huang, E. Sandifer, K. Hebert, E. W. Barnes, R. Hubley, W. Miller, A. F. Smit, B. Ullmer, and M. A. Batzer. 2007
Mobile DNA in Old World monkeys: a glimpse through the rhesus macaque genome. Science 316:238-240.
Abstract:
The completion of the draft sequence of the rhesus macaque genome allowed us to study thegenomic composition and evolution of transposable elements in this representative of the OldWorld monkey lineage, a group of diverse primates closely related to humans. The L1 family oflong interspersed elements appears to have evolved as a single lineage, and Alu elements haveevolved into four currently active lineages. We also found evidence of elevated horizontaltransmissions of retroviruses and the absence of DNA transposon activity in the Old World monkeylineage. In addition, ~100 precursors of composite SVA (short interspersed element, variablenumber of tandem repeat, and Alu) elements were identified, with the majority being shared by thecommon ancestor of humans and rhesus macaques. Mobile elements compose roughly 50% ofprimate genomes, and our findings illustrate their diversity and strong influence on genomeevolution between closely related species.
Supplemental Data:
Supplemental Data.pdf
Supplemental data files.zip
Potentially Retrotansposition-Competent Macaque L1 Elements.docx
193
Gibbs et al. 2007
Evolutionary and biomedical insights from the rhesus macaque genome. Science 316:222-234.
Full Citation:
Gibbs, R. A., J. Rogers, M. G. Katze, R. Bumgarner, G. M. Weinstock, E. R. Mardis, K. A. Remington, R. L. Strausberg, J. C. Venter, R. K. Wilson, M. A. Batzer, C. D. Bustamante, E. E. Eichler, M. W. Hahn, R. C. Hardison, K. D. Makova, W. Miller, A. Milosavljevic, R. E. Palermo, A. Siepel, J. M. Sikela, T. Attaway, S. Bells, K. E. Bernard, C. J. Buhay, M. N. Ch, rabose, M. Dao, C. Davis, K. D. Delehaunty, Y. Ding, H. H. Dinh, S. Dugan-Rocha, L. A. Fulton, R. A. Gabisi, T. T. Garner, J. Godfrey, A. C. Hawes, J. Hern, ez, S. Hines, M. Holder, J. Hume, S. N. Jhangiani, V. Joshi, Z. M. Khan, E. F. Kirkness, A. Cree, R. G. Fowler, S. Lee, L. R. Lewis, Z. Li, Y. S. Liu, S. M. Moore, D. Muzny, L. V. Nazareth, D. N. Ngo, G. O. Okwuonu, G. Pai, D. Parker, H. A. Paul, C. Pfannkoch, C. S. Pohl, Y. H. Rogers, S. J. Ruiz, A. Sabo, J. Santibanez, B. W. Schneider, S. M. Smith, E. Sodergren, A. F. Svatek, T. R. Utterback, S. Vattathil, W. Warren, C. S. White, A. T. Chinwalla, Y. Feng, A. L. Halpern, L. W. Hillier, X. Huang, P. Minx, J. O. Nelson, K. H. Pepin, X. Qin, G. G. Sutton, E. Venter, B. P. Walenz, J. W. Wallis, K. C. Worley, S. P. Yang, S. M. Jones, M. A. Marra, M. Rocchi, J. E. Schein, R. Baertsch, L. Clarke, M. Csürös, J. Glasscock, R. A. Harris, P. Havlak, A. R. Jackson, H. Jiang, Y. Liu, D. N. Messina, Y. Shen, H. X. Song, T. Wylie, L. Zhang, E. Birney, K. Han, M. K. Konkel, J. Lee, A. F. Smit, B. Ullmer, H. Wang, J. Xing, R. Burhans, Z. Cheng, J. E. Karro, J. Ma, B. Raney, X. She, M. J. Cox, J. P. Demuth, L. J. Dumas, S. G. Han, J. Hopkins, A. Karimpour-Fard, Y. H. Kim, J. R. Pollack, T. Vinar, C. Addo-Quaye, J. Degenhardt, A. Denby, M. J. Hubisz, A. Indap, C. Kosiol, B. T. Lahn, H. A. Lawson, A. Marklein, R. Nielsen, E. J. Vallender, A. G. Clark, B. Ferguson, R. D. Hern, ez, K. Hirani, H. Kehrer-Sawatzki, J. Kolb, S. Patil, L. L. Pu, Y. Ren, D. G. Smith, D. A. Wheeler, I. Schenck, E. V. Ball, R. Chen, D. N. Cooper, B. Giardine, F. Hsu, W. J. Kent, A. Lesk, D. L. Nelson, W. E. O'Brien, K. Prüfer, P. D. Stenson, J. C. Wallace, H. Ke, X. M. Liu, P. Wang, A. P. Xiang, F. Yang, G. P. Barber, D. Haussler, D. Karolchik, A. D. Kern, R. M. Kuhn, K. E. Smith, and A. S. Zwieg. 2007
Evolutionary and biomedical insights from the rhesus macaque genome. Science 316:222-234.
Abstract:
The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from theancestors of Homo sapiens about 25 million years ago. Because they are genetically andphysiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate inbasic and applied biomedical research. We determined the genome sequence of an Indian-originMacaca mulatta female and compared the data with chimpanzees and humans to reveal thestructure of ancestral primate genomes and to identify evidence for positive selection and lineagespecificexpansions and contractions of gene families. A comparison of sequences from individualanimals was used to investigate their underlying genetic diversity. The complete description of themacaque genome blueprint enhances the utility of this animal model for biomedical research andimproves our understanding of the basic biology of the species.
Supplemental Data:
Supplemental Data.pdf
Polymorphic LINE Primer Conditions.xls
Polymorphic Alu Primer Conditions.xls
Polymorphic Alu Allele Frequencies.xls
2006
177
Xing et al. 2006
Emergence of primate genes by retrotransposon-mediated sequence transduction. Proceedings of the National Academy of Sciences, USA 103:17608-17613.
Full Citation:
Xing, J., H. Wang, V. P. Belancio, R. Cordaux, P. L. Deininger, and M. A. Batzer. 2006
Emergence of primate genes by retrotransposon-mediated sequence transduction. Proceedings of the National Academy of Sciences, USA 103:17608-17613.
Abstract:
Gene duplication is one of the most important mechanisms for creating new genes and generating genomic novelty. Retrotransposon-mediated sequence transduction (i.e., the process by which a retrotransposon carries flanking sequence during its mobilization) has been proposed as a gene duplication mechanism. L1 exon shuffling potential has been reported in cell culture assays, and two potential L1-mediated exon shuffling events have been identified in the genome. SVA is the youngest retrotransposon family in primates and is capable of 3' flanking sequence transduction during retrotransposition. In this study, we examined all of the full-length SVA elements in the human genome to assess the frequency and impact of SVA-mediated 3' sequence transduction. Our results showed that approximately 53 kb of genomic sequences have been duplicated by 143 different SVA-mediated transduction events. In particular, we identified one group of SVA elements that duplicated the entire AMAC gene three times in the human genome through SVA-mediated transduction events, which happened before the divergence of humans and African great apes. In addition to the original AMAC gene, the three transduced AMAC copies contain intact ORFs in the human genome, and at least two are actively transcribed in different human tissues. The duplication of entire genes and the creation of previously undescribed gene families through retrotransposon-mediated sequence transduction represent an important mechanism by which mobile elements impact their host genomes.
Supplemental Data:
Supplemental Data.rar
174
Cordaux et al. 2006
Birth of a chimeric primate gene by capture of the transposase gene from a mobile element. Proceedings of the National Academy of Sciences, USA 103:8101-8106.
Full Citation:
Cordaux, R., S. Udit, M. A. Batzer, and C. Feschotte. 2006
Birth of a chimeric primate gene by capture of the transposase gene from a mobile element. Proceedings of the National Academy of Sciences, USA 103:8101-8106.
Abstract:
The emergence of new genes and functions is of central importance to the evolution of species. The contribution of various types of duplications to genetic innovation has been extensively investigated. Less understood is the creation of new genes by recycling of coding material from selfish mobile genetic elements. To investigate this process, we reconstructed the evolutionary history of SETMAR, a new primate chimeric gene resulting from fusion of a histone methyltransferase gene to the transposase gene of a mobile element. We show that the transposase gene was recruited as part of SETMAR 40-58 million years ago, after the insertion of an Hsmar1 transposon downstream of a preexisting SET gene, followed by the de novo exonization of previously noncoding sequence and the creation of a new intron. The original structure of the fusion gene is conserved in all anthropoid lineages, but only the N-terminal half of the transposase is evolving under strong purifying selection. In vitro assays show that this region contains a DNA-binding domain that has preserved its ancestral binding specificity for a 19-bp motif located within the terminal-inverted repeats of Hsmar1 transposons and their derivatives. The presence of these transposons in the human genome constitutes a potential reservoir of ~ 1,500 perfect or nearly perfect SETMAR-binding sites. Our results not only provide insight into the conditions required for a successful gene fusion, but they also suggest a mechanism by which the circuitry underlying complex regulatory networks may be rapidly established.
Supplemental Data:
Supplemental Table 1.pdf
Supplemental Table 2.pdf
Supplemental Table 3.pdf
Supplemental Table 4.pdf
Supplemental Figure 4.pdf
Supplemental Figure 5.pdf
Supplemental Figure 6.pdf
Supplemental Figure 7.pdf
This week in PNAS.pdf
Commentary.pdf
164
Cordaux and Batzer 2006
Teaching an old dog new tricks: SINEs of canine genomic diversity. Proceedings of the National Academy of Sciences, USA 103:1157-1158 [commentary].
Full Citation:
Cordaux R., and M. A. Batzer. 2006
Teaching an old dog new tricks: SINEs of canine genomic diversity. Proceedings of the National Academy of Sciences, USA 103:1157-1158 [commentary].
Abstract:
None available
Supplemental Data:
None.
2005
163
Wang^, Xing^ and Grover^ et al. 2005
SVA elements: a hominid specific retroposon family. Journal of Molecular Biology 354:994-1007.
Full Citation:
Wang^, H., J. Xing^, D. Grover^, D. J. Hedges, K. Han, J. A. Walker, and M. A. Batzer. 2005
SVA elements: a hominid specific retroposon family. Journal of Molecular Biology 354:994-1007.
Abstract:
SVA is a composite repetitive element named after its main components, SINE, VNTR and Alu. We have identified 2762 SVA elements from thehuman genome draft sequence. Genomic distribution analysis indicates that the SVA elements are enriched in GCC-rich regions but have nopreferences for inter- or intragenic regions. A phylogenetic analysis of the elements resulted in the recovery of six subfamilies that were namedSVA_A to SVA_F. The composition, age and genomic distribution of the subfamilies have been examined. Subfamily age estimates based uponnucleotide divergence indicate that the expansion of four SVA subfamilies (SVA_A, SVA_B, SVA_C and SVA_D) began before the divergence ofhuman, chimpanzee and gorilla, while subfamilies SVA_E and SVA_F are restricted to the human lineage. A survey of human genomic diversityassociated with SVA_E and SVA_F subfamily members showed insertion polymorphism frequencies of 37.5% and 27.6%, respectively. In addition,we examined the amplification dynamics of SVA elements throughout the primate order and traced their origin back to the beginnings of hominidprimate evolution, approximately 18 to 25 million years ago. This makes SVA elements the youngest family of retroposons in the primate order.
Supplemental Data:
Cover Legend.doc
Supplemental Table 1.xls
Supplemental Table 2.xls
Supplemental Alignment.txt
Supplemental Figure 1.tif
SVA elements present in 5 Kb upstream region of human genes.txt
151
Han^ and Xing^ et al. 2005
Under the genomic radar: the stealth model of Alu amplification. Genome Research 15:655-664.
Full Citation:
Han^, K., J. Xing^, H. Wang, D. J. Hedges, R. K. Garber, R. Cordaux, and M. A. Batzer. 2005
Under the genomic radar: the stealth model of Alu amplification. Genome Research 15:655-664.
Abstract:
Alu elements are the most successful SINEs (Short INterspersed Elements) in primate genomes and have reached morethan 1,000,000 copies in the human genome. The amplification of most Alu elements is thought to occur through alimited number of hyperactive "master" genes that produce a high number of copies during long evolutionaryperiods of time. However, the existence of long-lived, low-activity Alu lineages in the human genome suggests a morecomplex propagation mechanism. Using both computational and wet-bench approaches, we reconstructed theevolutionary history of the AluYb lineage, one of the most active Alu lineages in the human genome. We show thatthe major AluYb lineage expansion in humans is a species-specific event, as nonhuman primates possess only ahandful of AluYb elements. However, the oldest existing AluYb element resided in an orthologous position in allhominoid primate genomes examined, demonstrating that the AluYb lineage originated 18-25 million years ago. Thus,the history of the AluYb lineage is characterized by ~20 million years of retrotranspositional quiescence preceding amajor expansion in the human genome within the past few million years. We suggest that the evolutionary success ofthe Alu family may be driven at least in part by "stealth-driver" elements that maintain low retrotranspositionalactivity over extended periods of time and occasionally produce short-lived hyperactive copies responsible for theformation and remarkable expansion of Alu elements within the genome.
Supplemental Data:
Cover Legend.doc
Supplemental data.zip
2002
105
Roy-Engel^ and Carroll^ et al. 2002
Non-traditional Alu evolution and primate genomic diversity. Journal of Molecular Biology 316:1033-1040.
Full Citation:
Roy-Engel^, A. M., M. L. Carroll^, M. El-Sawy, A.-H. Salem, R. K. Garber, S. V. Nguyen, P. L. Deininger, and M. A. Batzer. 2002
Non-traditional Alu evolution and primate genomic diversity. Journal of Molecular Biology 316:1033-1040.
Abstract:
Alu elements belonging to the previously identified "young" subfamilies are thought to have inserted in the human genome after the divergence of humans from non-human primates and therefore should not be present in non-human primate genomes. Polymerase chain reaction (PCR) based screening of over 500 Alu insertion loci resulted in the recovery of a few "young" Alu elements that also resided at orthologous positions in non-human primate genomes. Sequence analysis demonstrated these "young" Alu insertions represented gene conversion events of pre-existing ancient Alu elements or independent parallel insertions of older Alu elements in the same genomic region. The level of gene conversion between Alu elements suggests that it may have a significant influence on the single nucleotide diversity within the genome. All the instances of multiple independent Alu insertions within the same small genomic regions were recovered from the owl monkey genome, indicating a higher Alu amplification rate in owl monkeys relative to many other primates. This study suggests that the majority of Alu insertions in primate genomes are the products of unique evolutionary events.
Supplemental Data:
None.
