Biochemistry and Molecular Biology
Penn State Science
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Stephan Schuster

Stephan Schuster

Main Content

  • Professor of Biochemistry and Molecular Biology
108 Althouse Laboratory
University Park, PA 16802

Research Interests

Genome evolution in host-adapted bacteria

Research Summary

Genome evolution in host-adapted bacteria


The availability of a large number of microbial genomes from a broad range of organisms has shaped our current understanding of the dynamics of genome structure from pathogenic and non-pathogenic bacteria. Such, it has been suggested that close adaptation towards a host in a symbiotic or pathogenic relationship results in small, minimalist genomes, which are required for survival in a host. Our group studies the genomes from related host-adapted and potentially free-living bacteria in order to gain insight into the molecular mechanisms that has driven the speciation process from free-living last common ancestors to the obligatory pathogenic species that we see today.

Epsilon-Proteobacteria show a highly variable genome structure
Our current understanding of bacterial pathogenicity mechanisms is largely based on the knowledge of the genomic inventory that is being shared by the most serious bacterial agents. Since many of these pathogenic organisms are strictly host-adapted, their genomes have undergone a degrading process leading to small, minimalist genomes. This process of deleting genetic information has resulted in orphaned cellular processes that can only be understood in their ancestral context. Such, to extend our knowledge on the origin and the emergence of a pathogen, it is essential to analyze the genomic inventory of living relatives with non-degraded genomes that have largely maintained the gene pool of a last common ancestor. Wolinella succinogenes, a rather unknown rumen dweller, is such an organism. Phylogenetically interspersed between Helicobacter pylori and Campylobacter jejuni, it constitutes an out-group to both pathogens, which have been demonstrated to cause serious illnesses in humans, such as gastric cancer or the Guillain-Barré -Syndrome. In our analysis, we show that the genome of W. succinogenes is 30% larger than those of H. pylori and C. jejuni. Since pseudo-genes were found to be rare in W. succinogenes, we believe its genome resides in a non-degrading state. A wealth of genetic information is found in addition to its relatives, which is highly reminiscent of free-living bacteria. This is particularly evident for genes that share a high degree of homology with cyanobacterial genes, such as a cluster of nif genes, as well as extended signaling networks. Surprisingly, the non-pathogenic W. succinogenes also contains complete sets of genes, which are homologous to known virulence factors and are clustered on genomic islands on the chromosome.

By a differential approach we now can identify genes that are unique in each of the three organisms and may confer host specificity to each of the organisms. Many of these species-specific genes co-localize with virulence genes on the chromosome and are therefore potential candidates for functional analysis.

By studying those genes that are being shared by all three organisms, we can identify essential molecular mechanisms used by symbiotic, commensal or pathogenic bacteria to maintain themselves in a vertebrate host environment.

The predatory bacterium Bdellovibrio keeps its genes to itself.
In a further approach we are testing whether results from the epsilon-proteobacterial system can be applied to other bacteria, which are not host-adapted to mammals, but rather more prey on other bacteria. The organism in question is called Bdellovibrio, which would translate into a "curved leech", a delta-Proteobacterium. In its lifecycle it depends on other Gram-negative bacteria for nutriment and building material. Bdellovibrio therefore invades its bacterial prey and devours it from inside, while initiating its own growth. Proteins, lipids and nucleotides of the host thereby serve as a substratum for the predator’s own growth and eventually the generation of several progeny.

Despite its life cycle being a parasitic one, Bdellovibrio has a twice as large genome compared to the one from pathogenic epsilon-Proteobacteria. A further striking difference is found in the almost complete absence of horizontal gene transfer (HGT) between the predator and the prey, which could mechanistically easily occur since the predator had direct access to the prey’s genetic information. Comparison of strains of Bdellovibrio, which are exclusively predatory or axenically growing, shows an unexpected stability of these genomes (e.g. lack of recombination).

Selected Publications

  • Calling SNPs without a reference sequence. (2010) A. Ratan , Y. Zhang , V.M. Hayes , S.C. Schuster and W. Miller  BMC Bioinformatics. March 15;11:130.
  • Interpretation of custom designed Illumina genotype cluster plots for targeted association studies and next-generation sequence validation. (2010) E.A. Tindall, D.C. Petersen DC, S. Nikolaysen, W. Miller, S.C. Schuster and V.M. Hayes BMC Res Notes. Feb 22;3(1):39.
  • Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear. (2010) C. Lindqvist*, S.C. Schuster*, Y. Sun, S.L. Talbot, J. Qi, A. Ratan, L.P. Tomsho, L.R. McKasson, E. Zey, J. Aars, W. Miller, Ó. Ingólfsson, L. Bachmann and Ø. Wiig (*equal contribution)  Proceedings of the National Academy of Sciences of the United States of America, March 16;107(11):5053-7.
  • Complete Khoisan and Bantu Genomes from Southern Africa. (2010) S.C. Schuster, W. Miller , A. Ratan, L.P. Tomsho, B. Giardine, L.R. Kasson, R.S. Harris, D.C. Petersen, F. Zhao, J. Qi, C. Alkan, J.M. Kidd, Y. Sun, D.I. Drautz, P. Bouffard, D.M. Muzny, J.G. Reid, L.V. Nazareth, Q. Wang, R. Burhans, C. Riemer, N.E. Wittekindt, P. Moorjani, E.A. Tindall, C.G. Danko, W.S. Teo, A.M. Buboltz, Z. Zhang, Q. Ma, A. Oosthuysen, A.W. Steenkamp, H. Oostuisen, P. Venter, J. Gajewski, Y. Zhang, B.F. Pugh, K.D. Makova, A. Nekrutenko, E.R. Mardis, N. Patterson, T.H. Pringle, F. Chiaromonte, J.C. Mullikin, E.E. Eichler, R.C. Hardison, R.A. Gibbs, T.T. Harkins, V.M. Hayes Nature, Feb 18;463(7283):943-947.
  • Genes acquired by horizontal transfer are potentially involved in the evolution of phytopathogenicity in Moniliophthora perniciosa and Moniliophthora roreri, two of the major pathogens of cacao. (2010) R.A. Tiburcio, G.G. Lacerda Costa, M.F. Carazzolle, J.M. Costa Mondego, S.C. Schuster, J.E. Carlson, M.J. Guiltinan, B.A. Bailey, P. Mieckowski, L.W. Meinhardt and G.A. Guimarães Pereira Journal of Molecular Evolution. Jan;70(1):85-97.
  • Optimization methods for selecting founder individuals for captive breeding or reintroduction of endangered species. (2009) Miller W, Wright SJ, Zhang Y, Schuster SC, Hayes VM. Pac Symp Biocomput. 2010:43-53.
  • Erythroid GATA1 function revealed by genome-wide analysis of transcription factor occupancy, histone modifications and mRNA expression. (2009) Y. Cheng, W. Wu, S.A. Kumar, D. Yu, Wulan Deng, T. Tripic, D.C. King, K.B. Chen, D.I.Drautz, S.C. Schuster, W. Miller, F. Chiaromonte, Y. Zhang, G.A. Blobel, M.J. Weiss, R.C. Hardison Genome Research. Dec;19(12):2172-84.
  • Genome 10K: A Proposition to Obtain Whole Genome Sequence for 10,000 Vertebrate Species. (2009) Genome 10K Community of Scientists (G10KCOS) and Authors Coordinators: D. Haussler, S.J. O'Brien, O.A. Ryder, Co-Authors: F.K. Barker, M. Clamp, A.J. Crawford, R. Hanner, O. Hubert Hanotte, W. Johnson, J. McGuire, W. Miller, R.W. Murphy, W.J. Murphy, F.H. Sheldon, B. Sinervo, B. Venkatesh, E.O. Wiley, F.W. Allendorf, S. Baker, G. Bernardi, S. Brenner, J. Cracraft, M. Diekhans, S. Edwards, J. Estes, P. Gaubert, A. Graphodatsky, J.A. Marshall Graves, E.D. Green, P. Hebert, K.M. Helgen, B. Kessing, D.M. Kingsley, H.A. Lewin, G. Luikart, Paolo Martelli, N. Nguyen, G. Orti, B.L. Pike, D.M. Rawson, S.C. Schuster, H.N. Seuánez, H.B. Shaffer, M.S. Springer, J.M. Stuart, E. Teeling, R.C. Vrijenhoek, R.D. Ward, R. Wayne, T.M. Williams, N.D. Wolfe, Y.P. Zhang Journal of Heredity. 100(6):659-674
  • Characterization of meiotic crossovers and gene conversion by whole-genome sequencing in Saccharomyces cerevisiae. (2009) J. Qi, A. Wijeratne, L.P. Tomsho, Y. Hu, S.C. Schuster and H. Ma BMC Genomics. Oct 15;10(1):475.
  • inGAP, an integrated next-gen genome analysis pipeline. (2009) J. Qi, F. Zhao, A. Buboltz, S.C. Schuster Bioinformatics. Jan 1;26(1):127-9.
  • Insights into the molecular basis of the microaerophily of three Campylobacterales: a comparative study. (2009) N.O. Kaakoush, C. Baar, L. Mackichan, P. Schmidt, E.M. Fox, S.C. Schuster, G.L. Mendz Antonie Van Leeuwenhoek. Nov;96(4):545-57.
  • Comparison of next generation sequencing technologies for transcriptome characterization. (2009) P.K. Wall, J. Leebens-Mack, A. Chanderbali, A. Barakat, E. Wolcott, H. Liang, L. Landherr, L.P Tomsho, Y. Hu, J.E. Carlson, H. Ma, S.C. Schuster, D.E. Soltis, P.S. Soltis, N. Altman and C.W. dePamphilis BMC Genomics. Aug 1;10:347
  • Tracking the past: Interspersed repeats in an extinct afrotherian mammal, Mammuthus primigenius. (2009) F. Zhao, J. Qi and S.C. Schuster Genome Research. Aug;19(8):1384-92.
  • Comparison of the complete genome sequences of Bifidobacterium animalis subsp. lactis DSM 10140 and Bl-04. (2009) R. Barrangou, E.P. Briczinski, L.L. Traeger, J.R. Loquasto, M. Richards, P. Horvath, A.C. Coûté-Monvoisin, G. Leyer, S.R. Rendulic, J.L. Steele, J.R. Broadbent, T. Oberg, E.G. Dudley, S.C. Schuster, D.A. Romero, R.F. Roberts Journal of Bacteriology. Jul;191(13), 4144-4151.
  • Analysis of Complete Mitochondrial Genomes from Extinct and Extant Rhinoceroses Reveals lack of phylogenetic resolution. (2009) E. Willerslev, M.T.P. Gilbert, J. Binladen, S. Ho, P.F. Campos, A. Ratan, L.P. Tomsho, R.R. da Fonseca, A. Sher, M. Nowak-Kemp, T. L. Roth, W. Miller and S.C. Schuster BMC Evolutionary Biology. May 11;9:95
  • Methods for comparative metagenomics. (2009) D.H. Huson, D.C. Richter, S. Mitra, A.F. Auch, S.C. Schuster BMC Bioinformatics. Jan 30;10 Suppl 1:S12.
  • The mitochondrial genome sequence of the Tasmanian tiger. (2009) W. Miller, D.I. Drautz, J.E. Janecka, A.M. Lesk, A. Ratan, L.P. Tomsho, M. Packard, Y. Zhang, L.R. McClellan, J. Qi, F. Zhao, M.T.P. Gilbert, L. Dalén, J.L. Arsuaga, P.G.P. Ericson, D.H. Huson, K.M. Helgen, W. Murphy, A. Götherström, S.C. Schuster Genome Research. Feb;19(2), 213-220.
  • Identification of microsatellites from an extinct moa species using high throughput (GS FLX) sequence data. (2009) M. Allentoft, S.C. Schuster, R. Holdaway, M. Hale, E. McLay, C. Oskam, M.T.P. Gilbert, P. Spencer, E. Willerslev and M. Bunce Biotechniques, 46(3):195-200.
  • Genome analysis of the meat starter culture Staphylococcus carnosus TM300. (2009) R. Rosenstein, C. Nerz, L. Biswas, A. Resch , G. Raddatz , S.C. Schuster and F. Götz Appl Environ Microbiol. Feb;75(3), 811-822.
  • Sequencing the Nuclear Genome of the Extinct Woolly Mammoth. (2008) W. Miller, D. Drautz, A. Ratan, B. Pusey, J. Qi, A.M. Lesk, L. Tomsho, M. Packard, F. Zhao, A. Sher, A. Tikhonov, B. Raney, N. Patterson, K. Lindblad-Toh, E.S. Lander, J.R. Knight, G.P. Irzyk, K.M. Fredrikson, T.T. Harkins, S. Sheridan, T. Pringle and S.C. Schuster Nature. Nov 20;456(7220), 387-390.