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International Research Training Group 1384 Enzymes and multienzyme complexes acting on nucleic acids Kolloquium der International Research Training Group GRK 1384 und der Gießener Biochemischen Institute Seminar on Wednesday the 30th of Nov. 2011 at 4 pm Speaker: Dr. Katja Nowick (TFome and Trancriptome Evolution, Universität Leipzig) Title: The role of transcription factors in human evolution Chair: Dr. Manja Marz (Institut für Pharmazeutische Chemie, Philipps-Universität Marburg) Venue: IMT, "Kleiner Hörsaal", Emil‐Mannkopff‐Str. 2, Marburg Guests are welcome. Coordination: Dr. Anja Drescher, Institut für Biochemie, FB 08, Heinrich-Buff-Ring 58, D-35392 Gießen, Tel. 0641-9935412, www.uni-giessen.de/biochem/grk1384 Abstract The role of transcription factors in human evolution Humans differ from other primates by a number of traits, for example their upright gait, their larger brain, and their cognitive abilities. What is the molecular basis for these phenotypic differences? Since differences in gene regulation are likely to play a major role in determining species differences, we focused on the evolution of transcription factor (TF) genes. We identified major changes in the repertoire of Krüppel-type zinc finger genes, the largest mammalian TF family, between primates, including lineage specific genes, pseudogenes, and sequence differences in the DNA-binding domain. We also discovered TFs with expression level differences between humans and chimpanzees, among which primate-specific TFs in the brain display the most pronounced differences. Interestingly, our computational network analysis further revealed that orthologous and paralogous TFs quickly diverge in their coexpression network partners, suggesting that they acquire new interaction partners and target genes. We speculate that such functional changes in TF genes are responsible for driving the evolution of human-specific traits. Coordination: Dr. Anja Drescher, Institut für Biochemie, FB 08, Heinrich-Buff-Ring 58, D-35392 Gießen, Tel. 0641-9935412, www.uni-giessen.de/biochem/grk1384 Curriculum Vitae Katja Nowick Current position: Research group leader „TFome and Transcriptome Evolution” University Leipzig D-04107 Leipzig, Germany Email: [email protected] Phone: 0341-9716684 Research fields: Molecular primate evolution Evolution of transcription factors and transcriptomes Comparative gene regulatory network analysis Functional characterization of genes in human and chimpanzee cell lines Membership: Since 2005 Society for Molecular Biology and Evolution (SMBE) Awarded research grants: 2011 Person exchange program ”Acções Integradas Luso-Alemãs” DAAD and the Portuguese FCT and CRUP “Genomic distribution of sequence and gene expression differences between mammalian species: the importance of chromosomal rearrangements in speciation” 2010 Advanced PostDoc fellowship for a junior research group Volkswagen foundation “Evolutionary and functional characterization of primate transcription factors (“TFome”)” Academic awards: 2007 ICAM travel award to attend the “Programming for Biology” course at the Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA 2006 Outstanding Abstract at Biosciences Directorate Symposium, Lawrence Livermore National Laboratory, Livermore, USA 2005 Best Poster Prize for Graduate Students at Annual Meeting of the Society for Molecular Biology and Evolutionary (SMBE), Auckland, New Zealand Research Experience: 2010 Max-Planck-Institute for Molecular Genetics, Berlin, Germany Determination of RUNX1 binding site by SELEX-Seq Analysis of haplotype-resolved human genomes 2008 – 2009 Institute for Genomic Biology, University of Illinois at UrbanaChampaign, IL, USA Evolutionary and functional characterization of Krüppel-type zinc finger genes Transcriptome variation among human individuals PI: Prof. Lisa Stubbs Coordination: Dr. Anja Drescher, Institut für Biochemie, FB 08, Heinrich-Buff-Ring 58, D-35392 Gießen, Tel. 0641-9935412, www.uni-giessen.de/biochem/grk1384 2006 – 2008 Lawrence Livermore National Laboratory, Livermore, CA, USA Evolution of expression differences and gene regulatory networks in primates PI: Dr. Lisa Stubbs 2001 – 2005 Max-Planck-Institute for Evolutionary Anthropology, Leipzig, Germany Functional analysis of FOXP2 in human cell lines Comparison of human and chimpanzee transcriptomes PI: Prof. Svante Pääbo Expression profiling during mouse brain development and identification of candidate genes important for neurogenesis and brain development PI: Prof. Wieland Huttner, Dr. Lilla Farkas 2000 – 2001 Dept. of Neuroimmunological Cell Biology, Interdisciplinary Center for Clinical Research, Leipzig, Germany Research assistant Study of rat primary neurons as model to investigate Alzheimer’s disease PI: Prof. Gerald Münch 1999 – 2000 Dept. of Neurobiology, University Leipzig, Leipzig, Germany Research assistant, diploma thesis Study of auditory discrimination abilities important for understanding speech in healthy human individuals PI: Prof. Rudolf Rübsamen Coordination: Dr. Anja Drescher, Institut für Biochemie, FB 08, Heinrich-Buff-Ring 58, D-35392 Gießen, Tel. 0641-9935412, www.uni-giessen.de/biochem/grk1384 Publications Nowick, K., Warnatz, H-J., Braun, H., Haas, S., Roider, S. Erdmann, V.A., Yaspo, M-L., Lehrach, H., Glökler, J. Comparative SELEX-Seq: In vitro selection of transcription factor binding sites using genomic and synthetic DNA libraries in combination with next generation sequencing. Genome Biology in review Nowick, K., Fields, C., Gernat, T., Caetano-Anolles, D., Kholina, N., Stubbs, L. (2011) Gain, loss and divergence in primate zinc-finger genes: a rich resource for evolution of gene regulatory differences between species, PLoS One 6: e21553 Suk, EK., McEwen, G.K., Duitama, J., Nowick, K., Schulz, S., Palczewski, S., Schreiber, S., Holloway, D., McLaughlin S., Peckham, H., Lee, C., Huebsch, T., and Hoehe, M.R. (2011) A comprehensively molecular haplotype-resolved genome of a European individual. Genome Research, Epub 2011/08/05 Nowick, K., Hamilton, A.T., Zhang, H., Tran-Gyamfi, M., and Stubbs, L. (2010) Rapid sequence and expression divergence suggests selection for novel function in primate-specific KRAB-ZNF transcription factors, Molecular Biology and Evolution Nowick, K. and Stubbs, L. Lineage-specific Transcription Factors and the Evolution of Gene Regulatory Networks, Briefings in Functional Genomics and Proteomics Nowick, K., Gernat, T., Almaas, E. and Stubbs, L. (2009) Differences in human and chimpanzee gene expression patterns define an evolving network of transcription factors in brain, Proc Natl Acad Sci USA Nowick, K., Huntley, S., and Stubbs, L. (2009) Rapid expansion and divergence suggest a central and distinct role for KRAB-ZNF genes in vertebrate evolution. In Yoshida, K. (ed), Focus on Zinc Finger Protein Research. Research Signpost, 13-29. Farkas, L.M., Haffner, C., Giger, T., Khaitovich, P., Nowick, K., Birchmeier, C., Paabo, S. and Huttner, W.B. (2008) Insulinoma-associated 1 has a panneurogenic role and promotes the generation and expansion of basal progenitors in the developing mouse neocortex, Neuron, 60, 40-55. Stroud, J.C., Wu, Y., Bates, D.L., Han, A., Nowick, K., Paabo, S., Tong, H. and Chen, L. (2006) Structure of the forkhead domain of FOXP2 bound to DNA, Structure, 14, 159-166. Khaitovich, P., Hellmann, I., Enard, W., Nowick, K., Leinweber, M., Franz, H., Weiss, G., Lachmann, M. and Paabo, S. (2005) Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees, Science, 309, 1850-1854. Coordination: Dr. Anja Drescher, Institut für Biochemie, FB 08, Heinrich-Buff-Ring 58, D-35392 Gießen, Tel. 0641-9935412, www.uni-giessen.de/biochem/grk1384