Faculty & Staff

  • Image of Kalin Vetsigian

    Kalin Vetsigian

    Assistant Professor of Bacteriology

    Wisconsin Institute for Discovery
    Systems Biology Theme, Room 3116
    Office: (608) 316-4670
    Lab: (608) 316-4319
    kalin@discovery.wisc.edu

Start and Promotion Dates

  • Assistant Professor: 2011

Education

BS 2000 MIT
PhD 2005 University of Illinois at Urbana-Champaign
Postdoctoral Research: Harvard Medical School

Research Overview

Nothing in biology makes sense except in light of evolution. At the same time, little in evolution makes sense outside the community context. Due to phenotypic interactions and genetic exchange, both selection and mutation pressures on organisms depend on what other organisms are around. To improve our understanding of the collective aspects of evolution, the lab studies the dynamics of microbial interactions in natural and synthetic microbial communities. We are primarily focused on bacteria from the genus Streptomyces because they are prolific producers of secondary metabolites, which mediate interactions, and because the genetic determinants of these interactions are hierarchically modular and subject to horizontal gene transfer. We develop protocols for quantifying the community dynamics at the phenotypic and genetic levels, and seek simplified theoretical models that reproduce aspects of the experimentally measured dynamics.

Research Papers

  • Kotil SE, Vetsigian K (2018) Emergence of evolutionarily stable communities through eco-evolutionary tunnelling. Nat Ecol Evol 2(10):1644-1653 10.1038/s41559-018-0655-7 · Pubmed

    Ecological and evolutionary dynamics of communities are inexorably intertwined. The ecological state determines the fate of newly arising mutants, and mutations that increase in frequency can reshape the ecological dynamics. Evolutionary game theory and its extensions within adaptive dynamics have been the mathematical frameworks for understanding this interplay, leading to notions such as evolutionarily stable states (ESS) in which no mutations are favoured, and evolutionary branching points near which the population diversifies. A central assumption behind these theoretical treatments has been that mutations are rare so that the ecological dynamics has time to equilibrate after every mutation. A fundamental question is whether qualitatively new phenomena can arise when mutations are frequent. Here, we describe an adaptive diversification process that robustly leads to complex ESS, despite the fact that such communities are unreachable through a step-by-step evolutionary process. Rather, the system as a whole tunnels between collective states over a short timescale. The tunnelling rate is a sharply increasing function of the rate at which mutations arise in the population. This makes the emergence of ESS communities virtually impossible in small populations, but generic in large ones. Moreover, communities emerging through this process can spatially spread as single replication units that outcompete other communities. Overall, this work provides a qualitatively new mechanism for adaptive diversification and shows that complex structures can generically evolve even when no step-by-step evolutionary path exists.

  • Xu Y, Vetsigian K (2017) Phenotypic variability and community interactions of germinating Streptomyces spores. Sci Rep 7(1):699 (PMC5429633) 10.1038/s41598-017-00792-7 · Pubmed

    A case can be made for stochastic germination and interactions among germinating spores as beneficial germination strategies in uncertain environments. However, there is little data on how widespread, species-specific or diverse such phenomena are. Focusing on Streptomycetes, a platform was developed for quantification of germination and early growth within communities of spores. We found that the germination process is stochastic at three levels: spores vary in their germination times, mycelium networks grow at different rates, and a fraction of germlings stall their growth shortly after germination. Furthermore, by monitoring how these stochastic properties are affected by spore density and chemicals released from spores, germination interactions were quantified for four species. Stochastically germinating spores were frequently promoted or inhibited by compounds released by spores from the same or different species, and all species had distinct interaction profiles. The spatial distribution patterns were important with clusters of spores behaving differently than individual spores. Aged spores exhibited higher dormancy but could efficiently geminate in the presence of chemicals released during germination. All interactions were specific to germination and only weakly affected growth rates. This work suggests that stochastic germination is commonly affected by the community context and species have adapted diverse germination strategies.

  • Baum DA, Vetsigian K (2016) Erratum to: An Experimental Framework for Generating Evolvable Chemical Systems in the Laboratory. Orig Life Evol Biosph 47(4):555 10.1007/s11084-016-9529-7 · Pubmed

    No abstract available.

  • Baum DA, Vetsigian K (2016) An Experimental Framework for Generating Evolvable Chemical Systems in the Laboratory. Orig Life Evol Biosph 47(4):481-497 (PMC5705744) 10.1007/s11084-016-9526-x · Pubmed

    Most experimental work on the origin of life has focused on either characterizing the chemical synthesis of particular biochemicals and their precursors or on designing simple chemical systems that manifest life-like properties such as self-propagation or adaptive evolution. Here we propose a new class of experiments, analogous to artificial ecosystem selection, where we select for spontaneously forming self-propagating chemical assemblages in the lab and then seek evidence of a response to that selection as a key indicator that life-like chemical systems have arisen. Since surfaces and surface metabolism likely played an important role in the origin of life, a key experimental challenge is to find conditions that foster nucleation and spread of chemical consortia on surfaces. We propose high-throughput screening of a diverse set of conditions in order to identify combinations of "food," energy sources, and mineral surfaces that foster the emergence of surface-associated chemical consortia that are capable of adaptive evolution. Identification of such systems would greatly advance our understanding of the emergence of self-propagating entities and the onset of adaptive evolution during the origin of life.

  • Wright ES, Vetsigian KH (2016) Quality filtering of Illumina index reads mitigates sample cross-talk. BMC Genomics 17(1):876 (PMC5097354) · Pubmed

    Multiplexing multiple samples during Illumina sequencing is a common practice and is rapidly growing in importance as the throughput of the platform increases. Misassignments during de-multiplexing, where sequences are associated with the wrong sample, are an overlooked error mode on the Illumina sequencing platform. This results in a low rate of cross-talk among multiplexed samples and can cause detrimental effects in studies requiring the detection of rare variants or when multiplexing a large number of samples. We observed rates of cross-talk averaging 0.24 % when multiplexing 14 different samples with unique i5 and i7 index sequences. This cross-talk rate corresponded to 254,632 misassigned reads on a single lane of the Illumina HiSeq 2500. Notably, all types of misassignment occur at similar rates: incorrect i5, incorrect i7, and incorrect sequence reads. We demonstrate that misassignments can be nearly eliminated by quality filtering of index reads while preserving about 90 % of the original sequences. Cross-talk among multiplexed samples is a significant error mode on the Illumina platform, especially if samples are only separated by a single unique index. Quality filtering of index sequences offers an effective solution to minimizing cross-talk among samples. Furthermore, we propose a straightforward method for verifying the extent of cross-talk between samples and optimizing quality score thresholds that does not require additional control samples and can even be performed post hoc on previous runs.

  • Wright ES, Vetsigian KH (2016) Inhibitory interactions promote frequent bistability among competing bacteria. Nat Commun 7:11274 (PMC4844671) · Pubmed

    It is largely unknown how the process of microbial community assembly is affected by the order of species arrival, initial species abundances and interactions between species. A minimal way of capturing competitive abilities in a frequency-dependent manner is with an invasibility network specifying whether a species at low abundance can increase in frequency in an environment dominated by another species. Here, using a panel of prolific small-molecule producers and a habitat with feast-and-famine cycles, we show that the most abundant strain can often exclude other strains--resulting in bistability between pairs of strains. Instead of a single winner, the empirically determined invasibility network is ruled by multiple strains that cannot invade each other, and does not contain loops of cyclic dominance. Antibiotic inhibition contributes to bistability by helping producers resist invasions while at high abundance and by reducing producers' ability to invade when at low abundance.

  • Wright ES, Vetsigian KH (2016) DesignSignatures: a tool for designing primers that yields amplicons with distinct signatures. Bioinformatics 32(10):1565-7 · Pubmed

    For numerous experimental applications, PCR primers must be designed to efficiently amplify a set of homologous DNA sequences while giving rise to amplicons with maximally diverse signatures. We developed DesignSignatures to automate the process of designing primers for high-resolution melting (HRM), fragment length polymorphism (FLP) and sequencing experiments. The program also finds the best restriction enzyme to further diversify HRM or FLP signatures. This enables efficient comparison across many experimental designs in order to maximize signature diversity. DesignSignatures is accessible as a web tool at www.DECIPHER.cee.wisc.edu, or as part of the DECIPHER open source software package for R available from BioConductor. kalin@discovery.wisc.edu Supplementary data are available at Bioinformatics online.

  • Kelsic ED, Zhao J, Vetsigian K, Kishony R (2015) Counteraction of antibiotic production and degradation stabilizes microbial communities. Nature 521(7553):516-9 (PMC4551410) · Pubmed

    A major challenge in theoretical ecology is understanding how natural microbial communities support species diversity, and in particular how antibiotic-producing, -sensitive and -resistant species coexist. While cyclic ‘rock–paper–scissors’ interactions can stabilize communities in spatial environments, coexistence in unstructured environments remains unexplained. Here, using simulations and analytical models, we show that the opposing actions of antibiotic production and degradation enable coexistence even in well-mixed environments. Coexistence depends on three-way interactions in which an antibiotic-degrading species attenuates the inhibitory interactions between two other species. These interactions enable coexistence that is robust to substantial differences in inherent species growth rates and to invasion by ‘cheating’ species that cease to produce or degrade antibiotics. At least two antibiotics are required for stability, with greater numbers of antibiotics enabling more complex communities and diverse dynamic behaviours ranging from stable fixed points to limit cycles and chaos. Together, these results show how multi-species antibiotic interactions can generate ecological stability in both spatially structured and mixed microbial communities, suggesting strategies for engineering synthetic ecosystems and highlighting the importance of toxin production and degradation for microbial biodiversity.

  • Chait R, Vetsigian K, Kishony R (2011) What counters antibiotic resistance in nature? Nat. Chem. Biol. 8(1):2-5 · Pubmed

    No abstract available.

  • Vetsigian K, Jajoo R, Kishony R (2011) Structure and evolution of streptomyces interaction networks in soil and in silico. PLoS Biol. 9(10):e1001184 (PMC3201933) · Pubmed

    No abstract available.

  • Tuller T, Carmi A, Vestsigian K, Navon S, Dorfan Y, Zaborske J, Pan T, Dahan O, Furman I, Pilpel Y (2010) An evolutionarily conserved mechanism for controlling the efficiency of protein translation. Cell 141(2):227-9 · Pubmed

    No abstract available.

  • Vetsigian K, Goldenfeld N (2009) Genome rhetoric and the emergence of compositional bias. Proc. Natl. Acad. Sci. U.S.A. 106(1):215-20 (PMC2629207) · Pubmed

    No abstract available.

  • DeLuna A, Vetsigian K, Shoresh N, Hegreness M, Colón-González M, Chao S, Kishony R (2008) Exposing the fitness contribution of duplicated genes. Nat. Genet. 40(5):676-81 · Pubmed

    No abstract available.

  • Bollenbach T, Vetsigian K, Kishony R (2007) Evolution and multilevel optimization of the genetic code. Genome Res. 17(4):401-4 · Pubmed

    No abstract available.

  • Vetsigian K, Woese C, Goldenfeld N (2006) Collective evolution and the genetic code. Proc. Natl. Acad. Sci. U.S.A. 103(28):10696-701 (PMC1502294) · Pubmed

    No abstract available.

  • Vetsigian K, Goldenfeld N (2005) Global divergence of microbial genome sequences mediated by propagating fronts. Proc. Natl. Acad. Sci. U.S.A. 102(20):7332-7 (PMC1129147) · Pubmed

    No abstract available.

  • Vetsigian K, Goldenfeld N (2003) Computationally efficient phase-field models with interface kinetics. Phys Rev E Stat Nonlin Soft Matter Phys 68(6 Pt 1):060601 · Pubmed

    No abstract available.