Mark Holder

Associate Professor
Associate Curator
Primary office:
Haworth Hall, room 6031


Dr. Holder develops statistical and computational approaches for estimating genealogical relationships.

My research revolves around statistical phylogenetics and its applications to evolutionary biology. In particular, I focus on Bayesian techniques for inferring phylogenies. I have contributed to development of Markov chain Monte Carlo methods used to implement Bayesian tree inference, but my primary interest is in the evolutionary models and prior assumptions that underlie these methods. Improvements to models allow us to estimate trees more accurately and assess the error in our estimates. More importantly, the development of richer models lets us use the comparative approach to a wide range of biological problems.

Current Activities/Research Program

Currently, I am working on a collaborative effort to improve the techniques available for multiple sequence alignment. My research group, along with collaborators at the University of Texas, University of Nebraska, University of Georgia, and Penn State University, will focus aligning sequences for the purposes of phylogenetic analysis. In particular, we will try to extend the realm of data set sizes for which it is feasible to use methods that simultaneously align sequences while searching for trees that best explain the data. The focus of the work here at KU will be on fast ways to approximate the maximum likelihood estimate of a phylogeny and history of insertions and deletions.

In the next phase of my research program, I will be building on the emerging field of context-dependent evolutionary models. Most phylogenetic models of sequence evolution make the unrealistic assumption that different sites evolve completely independently of each other. Building on recent Markov chain Monte Carlo techniques (Jensen and Pedersen, Advances in Applied Probability, 32, 2000), researchers have begun to explore models that consider constraints on the entire sequence. For example, the requirement that a protein must fold into a particular three-dimensional structure in order to function, constraints the amino acids that are allowed in a sequence. A mutation in one site may change the state-space of residues allowed at its neighbor (or an interacting site in the folded configuration). Initial efforts to construct phylogenetic models to explicitly accommodate the influence of protein tertiary structure (for examples see Robinson et al., Molecular Biology and Evolution, 20, 2003; Rodrigue et al., Gene, 347,2005; but also see Thorne et al., Molecular Biology and Evolution, 24, 2007). My work will focus on modeling the constraints on protein evolution more accurately. I am also interested in applying this class of context-dependent model to the analysis of morphological character evolution.

Selected Publications

  • Redelings, B.R. and Holder, M.T. (2019).  Taxonomic Supertree construction with incertae sedis taxa. In: T. J. Warnow (ed). Bioinformatics and Phylogenetics. Springer Books.
  • Redelings, B. D., & Holder, M. T. (2017). A supertree pipeline for summarizing phylogenetic and taxonomic information for millions of species. PeerJ.
  • McTavish, E. J., Steel, M., and Holder, M. T. (2015). Twisted trees and inconsistency of tree estimation when gaps are treated as missing data – The impact of model misspecification in distance corrections. Molecular Phylogenetics and Evolution, 93, 289 - 295. doi: ISSN: 1055-7903
  • McTavish, E. J. B., Hinchliff, C., Allman, J., Brown, J., Cranston, K., Holder, M. T., Rees, J., and Smith, S. A. (2015). Phylesystem: a git-based data store for community curated phylogenetic estimates. Bioinformatics 31(17): 2794-2800.  doi:10.1093/bioinformatics/btv27
  • Lewis, P. O., Holder, M. T., and Swofford, D. 2015. Phycas: Software for Bayesian Phylogenetic Analysis. Systematic Biology 64(3): 525-531. doi:10.1093/sysbio/syu132
  • Holder, M. T., Lewis, P. O., Swofford, D. L., and Bryant, D. 2014. Variable tree topology stepping stone marginal likelihood estimation. In Bayesian phylogenetics: methods, algorithms, and applications. ISBN: 9781466500792.
  • Oaks, J. R., J. A. Sukumaran, J. A. Esselstyn, C. W. Linkem, C. D. Siler, M. T. Holder, and R. M. Brown. 2013. "Evidence for climate-driven diversification? A caution for interpreting ABC inferences of simultaneous historical events." Evolution. 67. 991–1010.
  • Liberles, D. A. et al. 2012. "The interface of protein structure, protein biophysics, and molecular evolution" Protein Science. 21(6). 769-785.
  • Liu, K., T. J. Warnow, M. T. Holder, S. Nelesen, J. Yu, A. Stamatakis, and C. R. Linder. 2012. "SATé-II: Very fast and accurate simultaneous estimation of multiple sequence alignments and phylogenetic trees" Systematic Biology. 61(1). 90-106.
  • Peterson, A. T. and M. T. Holder. 2012. "Phylogenetic assessment of filoviruses: How many lineages of Marburgvirus?" Ecology and Evolution. 2. 1826-1833.
  • Vos, R. A. et al. 2012. "NeXML: Rich, extensible, and verifiable representation of comparative data and metadata" Systematic Biology. 61(4). 675-689.
  • Ayres, D. L. et al. 2012. "BEAGLE: An application programming interface and high-performance computing library for statistical phylogenetics" Systematic Biology. 61(1). 170-173.
  • Koch, J. M. and M. T. Holder. 2012. "An algorithm for calculating the probability of classes of data patterns on a genealogy" PLOS Currents Tree of Life.
  • Heath, T. A., M. T. Holder, and J. P. Huelsenbeck. 2012. "A Dirichlet process prior for estimating lineage-specific substitution rates" Molecular Biology and Evolution. 29(3). 939-955.
  • Lakner, C., M. T. Holder, N. Goldman, and G. J. P. N. Naylor. 2011. "What’s in a likelihood? Simple models of protein evolution and the contribution of structurally viable reconstructions to the likelihood" Systematic Biology. 60(2). 161-174.
  • Edgcomb, V. et al. 2011. "Protistan microbial observatory in the Cariaco Basin, Caribbean. I. species richness and endemicity" ISME Journal. 5(8). 1344-1356.
  • Sukumaran, J. A. and M. T. Holder. 2011. "Ginkgo: spatially-explicit simulator of complex phylogeographic histories" Molecular Ecology Resources. 11(2). 364-369.
  • Holder, M. T. and M. Steel. 2011. "Estimating phylogenetic trees from pairwise likelihoods and posterior probabilities of substitution counts" Journal of Theoretical Biology. 280(1). 159-166.
  • Evans, N. M., M. T. Holder, M. S. Barbeitos, B. Okamura, and P. Cartwright. 2010. "The phylogenetic position of Myxozoa: Exploring conflicting signals in phylogenomic and ribosomal data sets" Molecular Biology and Evolution. 27(12). 2733-2746.
  • Peterson, A. T., S. Knapp, R. P. Guralnick, J. M. Soberón, and M. T. Holder. 2010. "The big questions for biodiversity informatics" Systematics and Biodiversity. 8(2). 159-168.
  • Holder, M. T., P. O. Lewis, and D. L. Swofford. 2010. "The Akaike information criterion will not choose the no common mechanism model" Systematic Biology. 59(4). 477–485.
  • Allman, E. S., M. T. Holder, and J. A. Rhodes. 2010. "Estimating trees from filtered data: Identifiability of models for morphological phylogenetics" Journal of Theoretical Biology. 263(1). 108-119.
  • Sukumaran, J. A. and M. T. Holder. 2010. "DendroPy: A Python library for phylogenetic computing" Bioinformatics. 26(12). 1569-1571.
  • Holder, M. T., J. A. Sukumaran, and R. M. Brown. 2010. "Bayesian Approaches to Phylogenetic Analysis" Bayesian Modeling in Bioinformatics. edited by Dey, D. K., S. Ghosh, and B. K. Mallick. 1-39.







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