RESEARCH

Comparative Genomics

Placental mammals display a staggering breadth of morphological, karyotypic, and genomic diversity, rivaling or surpassing any other living vertebrate clade. This variation represents the culmination of one hundred million years of diversification and parallel adaptation to tumultuous changes in Earth’s environments, including catastrophic events like the Cretaceous-Paleogene (KPg) bolide impact. Comparative genomic approaches can leverage this diversity to understand the genomic basis of extraordinary mammalian adaptations, inform conservation management plans and glean novel insights of benefit to medical research.

Recent Publications

  1. Dindot, S.V., Christian, S., Murphy W.J., Berent, A., Panagoulias, J., Shlafer, A., Ballard, J., Radeva, K., Robinson, R., Myers, L., Jepp, T., Shaheen, H., Hillman, P., Kongati, K., Hillhouse, A., Bredemeyer, K.R., Black, L., Douville, J., and the FIRE Consortium. Development of an ASO therapy for Angelman syndrome by targeting a conserved region at the start of the UBE3A-AS transcript. Science Translational Medicine [Accepted] bioRxiv https://doi.org/10.1101/2021.07.27.453820
  2. Harris, A.J., Foley, N.M., Williams, T., and W.J. Murphy. 2022. TreeHouseExplorer (THEx): A novel genome browser for phylogenomics. Molecular Biology and Evolution  doi: 10.1093/molbev/msac130.
  3. Brashear, W.A., Bredemeyer, K.R., and W. J. Murphy. 2021. Genomic architecture constrained placental mammal X chromosome evolution. Genome Research 31: 1353-1365.
  4. Genereux D.P., Serres, A., Armstrong, J., Johnson, J., Marinescu, V.D., Murén, E., deJuan, D., Bejerano, G., Casewell, N.R., Chemnick, L.G., Damas, J., Di Palma, F., Diekhans, M., Fiddes, I.T., Garber, M., Goodman, L., Haerty, W., Houck, M.L., Hubley, R.L., Kivioja, T., Kuderna, L., Lander, E.S., Marques-Bonet, T., Meadows, J.R.S., Murphy, W.J., Nash, W., Noh, H.J., Nweeia, M., Pfenning, A.R., Pollard, K., Ray, D., Shapiro, B., Smit, A., Springer, M.S., Steiner, C.S., Swofford, R., Taipale, J., Teeling, E.C., Turner-Maier, J., Alfoldi, J., Birren, B., Ryder, O.A., Lewin, H.A., Paten, B., Lindblad-Toh, K., and Karlsson, E.K. (Zoonomia Consortium) 2020. A comparative genomics multitool for scientific discovery and conservation. Nature 587: 240-245.
  5. Beichman, A.C., Koepfli, K.-P., Li G., Murphy, W., Dobrynin, P., Kilver, S., Tinker, T., Schenck, C., Schenck, E., Johnson, J., Karlsson, E., Estes, J., Lohmueller, K., and R.K. Wayne. 2019. Aquatic adaptation and depleted diversity: a deep dive into the genomes of the sea otter (Enhydra lutris) and giant otter (Pteronura brasiliensis). Molecular Biology and Evolution. 36: 2631-2655.

Classics

  1. Janečka, J. E., Miller, W., Pringle, T. H., Wiens, F., Zitzmann, A., Helgen, K. M., Springer, M. S., and W. J. Murphy.  2007. Molecular and genomic data identify the closest living relative of primates. Science 318: 792-794.
  2. Murphy, W. J., Larkin, D., Everts van-der Wind, A., Bourque, G., Tesler, G., Auvil, L., Beever, J. E., Chowdhary, B. P., Galibert, F., Gatzke, L., Hitte, C., Meyers, S. N., Ostrander, E. A., Pape, G., Parker, H. G., Raudsepp, T., Rogatcheva, M. B., Schook, L. B., Skow, L. C., Welge, M., Womack, J. E., O’Brien, S. J., Pevzner, P. A., H. A. Lewin. 2005. Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps. Science 309: 613-617.
  3. Murphy, W. J., Pevzner, P. and S. J. O’Brien.  2004. Mammalian phylogenomics comes of age. Trends in Genetics 20: 631-639.

Felid Biomedical and Evolutionary Genomics

A major focus in the lab is developing and applying genomic resources for the cat family to connect genotype to phenotype, and reveal the evolutionary consequences of historical and contemporary hybridization between species.

Recent Publications

  1. Myers, A.N., Lawhon, S.D., Diesel, A.B., Liu, W., Rodrigues Hoffmann, A., 99Lives Genome Consortium, and W.J. Murphy. 2022. An ancient haplotype containing antimicrobial peptide genes is associated with severe fungal skin disease in Persian cats. PLoS Genetics 18(2): e1010062.
  2. Bredemeyer, K.R., Seabury, C.M., Stickney, M.J., McCarrey, J.R., vonHoldt, B.M., and W.J. Murphy. 2021. Rapid macrosatellite evolution promotes X-linked hybrid male sterility in a feline interspecies cross. Molecular Biology and Evolution 38: 5588-5609.
  3. Bredemeyer, K.R., Harris, A.J., Li, G., Zhao, L., Foley, N.M., Roelke-Parker, M.E., O’Brien, S.J., Lyons, L.A., Warren, W.C., and W.J. Murphy. 2021. Ultracontinuous single haplotype genome assemblies for the domestic cat (Felis catus) and Asian leopard cat (Prionailurus bengalensis). Journal of Heredity 112: 165-173.
  4. Buckley, R.M., Davis, B.W., Brashear, W.A., Farias, F.H.G., Kuroki, K., Graves, T., Hillier, L.W., Kremitzki, M., Li, G., Middleton, R., Minx, P., Tomlison, C., Lyons, L.A., Murphy, W.J., Warren, W.C. 2020. A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism. PLOS Genetics 16(10): e1008926.
  5. Bugno-Poniewierska, M., Kij, B., Witarski, W., Wojtaszek M., Radko, A., Podbielska, A., Izabela, S., and W.J. Murphy. 2020. Fertile male tortoiseshell cat with true chimerism 38,XY/38,XY. Reproduction in Domestic Animals 55: 1139-1144.

Classics

  1. Montague, M., Li, G., Gandolfi, B., Khan, R., Aken, B.L., Searle, S.M.J., Minx, P., Hillier, L., Kolboldt, D.C., Davis, B.W., Driscoll, C.A., Barr, C., Blackstone, K., Quilez, J., Lorente-Galdos, B., Marques-Bonet, T., Alkan, C., Thomas G.W.C., Hahn, M.W., Menotti-Raymond, M., O’Brien, S.J., Wilson, R.K., Lyons, L.A., Murphy, W.J., and W. C. Warren. 2014. Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication. Proceedings of the National Academy of Sciences USA 111: 17230-17235.
  2. Davis, B. W., Raudsepp, T., Pearks Wilkerson, A. J., Agarwala, R., Schäffer, A. A., Houck, M., Chowdhary, B. P., and W.J. Murphy. 2009. A high-resolution cat radiation hybrid and integrated FISH mapping resource for phylogenomic studies across Felidae. Genomics 93: 299-304.
  3. Murphy, W.J., Sun, S., Chen, Z.-Q., Yuhki, N., Hirschmann, D. A., Menotti-Raymond, M., and S. J. O’Brien.  2000.  A radiation hybrid map of the cat genome: implications for comparative mapping. Genome Research 10: 691-702.

Phylogenetics, Phylogeography and Conservation Genomics

We use phylogenetic approaches to understand when and how mammals diversified, and to aid in the delimitation of species and conservation units for management.

Recent Publications

  1. Foley, N.M., Mason, V.C., Harris, A.J., Bredemeyer, K.R., Damas, J., Lewin, H.A., Eizirik, E., Gatesy, J., Karlsson E., Lindblad-Toh, K., Zoonomia Consortium, Springer, M.S., and W.J. Murphy. A genomic timescale for placental mammal evolution. Science [In press] Preprint on bioRxiv 10.1101/2022.08.10.503388
  2. Trindade, F.J., Rodrigues, M.R., Figueiró, H.V., Li, G., Murphy, W.J., and E. Eizirik. 2021. Genome-wide SNP data help disentangle a complex felid radiation and support recognition of an additional species of wild cat. Molecular Biology and Evolution 38: 4987-4991.
  3. Murphy, W.J., Foley, N.M., Bredemeyer, K.R., Gatesy, J., and M.S. Springer. 2021. Phylogenomics and the genetic architecture of the placental mammal radiation. Annual Review of Animal Biosciences 9: 29-53.
  4. Li, G., Figueiró, H.X., Eizirik, E., and W.J. Murphy. 2019. Recombination-aware phylogenomics reveals the structured genomic landscape of hybridizing cat species. Molecular Biology and Evolution. 36: 2111-2126.
  5. Mason, V.C., Helgen, K.M., and W.J. Murphy. 2019. Comparative phylogeography of forest-dependent mammals reveals paleo-forest corridors throughout Sundaland. Journal of Heredity  110: 158-172.

Classics

  1. Meredith, R. W., Janečka, J.E, Gatesy, J., Ryder, O. A., Fisher, C.A., Teeling, E.C., Goodbla, A., Eizirik, E., Simão, T. L. L., Stadler, T., Rabosky, D. L., Honeycutt, R. L., Flynn, J. J., Ingram, C. M., Steiner, C., Williams, T. L., Robinson, T. J., Burk-Herrick, A., Westerman, M., Ayoub, N. A., Springer, M. S., and W. J. Murphy. 2011. Impacts of the Cretaceous Terrestrial Revolution and KPg Extinction on mammal diversification. Science 334: 521-525.
  2. Teeling, E. C., Springer, M. S., Madsen, O., Bates, P., O’Brien, S. J., and W. J. Murphy. 2005. A molecular phylogeny for bats illuminates biogeography and the fossil record. Science 307: 580-584.
  3. Murphy, W. J., Eizirik, E., Johnson, W. J., Zhang, Y. P., Ryder, O. A., and S. J. O’Brien.  2001.  Molecular phylogenetics and the origins of placental mammals. Nature 409: 614-618.