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Faculty & Staff

Start and Promotion Dates

  • Assistant Professor: 2021

Education

PhD: Emory University, Department of Chemistry
Postdoctoral research: NASA Astrobiology Institute and Harvard University

Areas of Study

Origins of life, astrobiology, early life and evolution, systems and synthetic biology, molecular paleobiology

Research Overview

The Kaçar Lab investigates the origins of life, the biology of early Earth and how understanding life’s emergence and early mechanisms may assist finding life beyond Earth. We are home to a NASA Astrobiology Center MUSE DISCOVERY to investigate the dynamics between environment, evolution and life. Our integrative approach enables the study of biomolecule-scale macroevolutionary trends that span billions of years of history and is a fundamentally new methodology with which to study the origins and early evolution of life. The overall goal of our work is to assess the possible environmental impacts of ancient enzymes on global-scale signatures that record biological activity. Our work has been recognized by various media outlets, such as the UN Women, UNICEF, Library of Congress, European Union Delegation on Education, NOVA Science, BBC, NPR Science Friday, MIT Technology Review, Vice News, Wired, PBS, CNN and others. 

 

For more please visit the following links:

 

Lab Personnel

Picture of Cuevas Zuviria
Bruno Cuevas Zuviria
Postdoc
cuevaszuviri@wisc.edu
Picture of Fer
Evrim Fer
Grad Student
fer@wisc.edu
Picture of Garcia
Amanda Garcia
Assistant Scientist
akgarcia3@wisc.edu
Picture of McGrath
Kaitlyn McGrath
Honorary Associate
kmcgrath5@wisc.edu

Research Papers

  • De Tarafder A, Parajuli NP, Majumdar S, Kaçar B, Sanyal S (2021) Kinetic Analysis Suggests Evolution of Ribosome Specificity in Modern Elongation Factor-Tus from "Generalist" Ancestors. Molecular biology and evolution 38((8)):3436-3444 PMC8321524 · Pubmed · DOI

    No abstract available.

  • Garcia AK, Cavanaugh CM, Kacar B (2021) The curious consistency of carbon biosignatures over billions of years of Earth-life coevolution. The ISME journal 15((8)):2183-2194 PMC8319343 · Pubmed · DOI

    No abstract available.

  • Carruthers BM, Garcia AK, Rivier A, Kacar B (2021) Automated Laboratory Growth Assessment and Maintenance of Azotobacter vinelandii. Current protocols 1((3)):e57 · Pubmed · DOI

    No abstract available.

  • Kaçar, B., Anbar, A. D., Garcia, A. K., Seefeldt, L. C., & Konhauser, K. O. (2021) Between a Rock and a Living Place: Natural Selection of Elements and the Search for Life in the Universe Bulletin of the AAS 53((4)): · DOI

    The suite of life’s essential chemical elements on Earth constitutes only one possible evolutionary outcome. A greater understanding of factors governing the natural selection of elements in Earth’s past will create a predictive capacity for detecting and assessing life’s existence on worlds where alternate evolutionary paths may have been taken.

  • Mainzer, A., Abell, P., Bannister, M. T., Barbee, B., Barnes, J., III, J. F. B., … Wright, E. L. (2021) The Future of Planetary Defense in the Era of Advanced Surveys Bulletin of the AAS 53((4)): · DOI

    Impacts due to near-Earth objects constitute a potentially preventable natural hazard. The first priority of planetary defense should be to complete a survey of objects large enough to cause severe regional damage, and to adequately fund characterization, modeling, and mitigation testing to address these rare but potentially catastrophic events.

  • Hand, K., Phillips, C. B., Chyba, C. F., Toner, B., Katija, K., Orphan, V., … Roussel, A. (2021) On the Past, Present, and Future Role of Biology in NASA’s Exploration of our Solar System Bulletin of the AAS 53((4)): · DOI

    Here we provide a brief perspective on the role of biology in NASA’s planetary science goals, and its spacecraft missions, past, present, and future. We argue that while biology — via astrobiology — generates much interest and excitement for NASA, biology is vastly under-represented as a science within NASA Planetary Science Division missions.

  • Engelhart, A., Blank, J. G., Carr, C., Cleaves, H. J., & Lynch, K. (2021) Astrobiology on habitable worlds: The case for considering prebiotic chemistry in mission design Bulletin of the AAS 53((4)): · DOI

    Laboratory-based studies of prebiotic chemistry — processes by which potential chemical precursors to life are produced — have provided insights into processes by which life could have emerged on early Earth. In this white paper, we describe how these insights provide actionable information that can inform the design of space exploration missions.

  • Goldman AD, Kacar B (2021) Cofactors are Remnants of Life's Origin and Early Evolution. Journal of molecular evolution 89((3)):127-133 PMC7982383 · Pubmed · DOI

    No abstract available.

  • Adam ZR, Fahrenbach AC, Jacobson SM, Kacar B, Zubarev DY (2021) Radiolysis generates a complex organosynthetic chemical network. Scientific reports 11((1)):1743 PMC7813863 · Pubmed · DOI

    No abstract available.

  • Kacar B, Garcia AK, Anbar AD (2020) Evolutionary History of Bioessential Elements Can Guide the Search for Life in the Universe. Chembiochem : a European journal of chemical biology 22((1)):114-119 · Pubmed · DOI

    No abstract available.

  • Venkataram S, Monasky R, Sikaroodi SH, Kryazhimskiy S, Kacar B (2020) Evolutionary stalling and a limit on the power of natural selection to improve a cellular module. Proceedings of the National Academy of Sciences of the United States of America 117((31)):18582-18590 PMC7414050 · Pubmed · DOI

    No abstract available.

  • Garcia AK, McShea H, Kolaczkowski B, Kaçar B (2020) Reconstructing the evolutionary history of nitrogenases: Evidence for ancestral molybdenum-cofactor utilization. Geobiology 18((3)):394-411 PMC7216921 · Pubmed · DOI

    No abstract available.

  • Liberles DA, Chang B, Geiler-Samerotte K, Goldman A, Hey J, Kaçar B, Meyer M, Murphy W, Posada D, Storfer A (2020) Emerging Frontiers in the Study of Molecular Evolution. Journal of molecular evolution 88((3)):211-226 PMC7386396 · Pubmed · DOI

    No abstract available.

  • Garcia AK, Kaçar B (2019) How to resurrect ancestral proteins as proxies for ancient biogeochemistry. Free radical biology & medicine 140:260-269 · Pubmed · DOI

    Throughout the history of life, enzymes have served as the primary molecular mediators of biogeochemical cycles by catalyzing the metabolic pathways that interact with geochemical substrates. The byproducts of enzymatic activities have been preserved as chemical and isotopic signatures in the geologic record. However, interpretations of these signatures are limited by the assumption that such enzymes have remained functionally conserved over billions of years of molecular evolution. By reconstructing ancient genetic sequences in conjunction with laboratory enzyme resurrection, preserved biogeochemical signatures can instead be related to experimentally constrained, ancestral enzymatic properties. We may thereby investigate instances within molecular evolutionary trajectories potentially tied to significant biogeochemical transitions evidenced in the geologic record. Here, we survey recent enzyme resurrection studies to provide a reasoned assessment of areas of success and common pitfalls relevant to ancient biogeochemical applications. We conclude by considering the Great Oxidation Event, which provides a constructive example of a significant biogeochemical transition that warrants investigation with ancestral enzyme resurrection. This event also serves to highlight the pitfalls of facile interpretation of paleophenotype models and data, as applied to two examples of enzymes that likely both influenced and were influenced by the rise of atmospheric oxygen - RuBisCO and nitrogenase.

  • Walker SI, Bains W, Cronin L, DasSarma S, Danielache S, Domagal-Goldman S, Kacar B, Kiang NY, Lenardic A, Reinhard CT, Moore W, Schwieterman EW, Shkolnik EL, Smith HB (2018) Exoplanet Biosignatures: Future Directions. Astrobiology 18((6)):779-824 PMC6016573 · Pubmed · DOI

    We introduce a Bayesian method for guiding future directions for detection of life on exoplanets. We describe empirical and theoretical work necessary to place constraints on the relevant likelihoods, including those emerging from better understanding stellar environment, planetary climate and geophysics, geochemical cycling, the universalities of physics and chemistry, the contingencies of evolutionary history, the properties of life as an emergent complex system, and the mechanisms driving the emergence of life. We provide examples for how the Bayesian formalism could guide future search strategies, including determining observations to prioritize or deciding between targeted searches or larger lower resolution surveys to generate ensemble statistics and address how a Bayesian methodology could constrain the prior probability of life with or without a positive detection. Key Words: Exoplanets-Biosignatures-Life detection-Bayesian analysis. Astrobiology 18, 779-824.

  • Kacar B, Guy L, Smith E, Baross J (2017) Resurrecting ancestral genes in bacteria to interpret ancient biosignatures. Philosophical transactions. Series A, Mathematical, physical, and engineering sciences 375((2109)): PMC5686408 · Pubmed · DOI

    Two datasets, the geologic record and the genetic content of extant organisms, provide complementary insights into the history of how key molecular components have shaped or driven global environmental and macroevolutionary trends. Changes in global physico-chemical modes over time are thought to be a consistent feature of this relationship between Earth and life, as life is thought to have been optimizing protein functions for the entirety of its approximately 3.8 billion years of history on the Earth. Organismal survival depends on how well critical genetic and metabolic components can adapt to their environments, reflecting an ability to optimize efficiently to changing conditions. The geologic record provides an array of biologically independent indicators of macroscale atmospheric and oceanic composition, but provides little in the way of the exact behaviour of the molecular components that influenced the compositions of these reservoirs. By reconstructing sequences of proteins that might have been present in ancient organisms, we can downselect to a subset of possible sequences that may have been optimized to these ancient environmental conditions. How can one use modern life to reconstruct ancestral behaviours? Configurations of ancient sequences can be inferred from the diversity of extant sequences, and then resurrected in the laboratory to ascertain their biochemical attributes. One way to augment sequence-based, single-gene methods to obtain a richer and more reliable picture of the deep past, is to resurrect inferred ancestral protein sequences in living organisms, where their phenotypes can be exposed in a complex molecular-systems context, and then to link consequences of those phenotypes to biosignatures that were preserved in the independent historical repository of the geological record. As a first step beyond single-molecule reconstruction to the study of functional molecular systems, we present here the ancestral sequence reconstruction of the beta-carbonic anhydrase protein. We assess how carbonic anhydrase proteins meet our selection criteria for reconstructing ancient biosignatures in the laboratory, which we term palaeophenotype reconstruction.This article is part of the themed issue 'Reconceptualizing the origins of life'.

  • Kacar B, Garmendia E, Tuncbag N, Andersson DI, Hughes D (2017) Functional Constraints on Replacing an Essential Gene with Its Ancient and Modern Homologs. mBio 8((4)): PMC5574714 · Pubmed · DOI

    Genes encoding proteins that carry out essential informational tasks in the cell, in particular where multiple interaction partners are involved, are less likely to be transferable to a foreign organism. Here, we investigated the constraints on transfer of a gene encoding a highly conserved informational protein, translation elongation factor Tu (EF-Tu), by systematically replacing the endogenous gene in the genome with its extant and ancestral homologs. The extant homologs represented variants from both near and distant homologous organisms. The ancestral homologs represented phylogenetically resurrected sequences dating from 0.7 to 3.6 billion years ago (bya). Our results demonstrate that all of the foreign genes are transferable to the genome, provided that an additional copy of the EF-Tu gene, , remains present in the genome. However, when the gene was removed, only the variants obtained from the gammaproteobacterial family (extant and ancestral) supported growth which demonstrates the limited functional interchangeability of with its homologs. Relative bacterial fitness correlated with the evolutionary distance of the extant homologs inserted into the genome. This reduced fitness was associated with reduced levels of EF-Tu and reduced rates of protein synthesis. Increasing the expression of partially ameliorated these fitness costs. In summary, our analysis suggests that the functional conservation of protein activity, the amount of protein expressed, and its network connectivity act to constrain the successful transfer of this essential gene into foreign bacteria. Horizontal gene transfer (HGT) is a fundamental driving force in bacterial evolution. However, whether essential genes can be acquired by HGT and whether they can be acquired from distant organisms are very poorly understood. By systematically replacing with ancestral homologs and homologs from distantly related organisms, we investigated the constraints on HGT of a highly conserved gene with multiple interaction partners. The ancestral homologs represented phylogenetically resurrected sequences dating from 0.7 to 3.6 bya. Only variants obtained from the gammaproteobacterial family (extant and ancestral) supported growth, demonstrating the limited functional interchangeability of with its homologs. Our analysis suggests that the functional conservation of protein activity, the amount of protein expressed, and its network connectivity act to constrain the successful transfer of this essential gene into foreign bacteria.

  • Kacar B, Hanson-Smith V, Adam ZR, Boekelheide N (2017) Constraining the timing of the Great Oxidation Event within the Rubisco phylogenetic tree. Geobiology 15((5)):628-640 PMC5575542 · Pubmed · DOI

    Ribulose 1,5-bisphosphate (RuBP) carboxylase/oxygenase (RuBisCO, or Rubisco) catalyzes a key reaction by which inorganic carbon is converted into organic carbon in the metabolism of many aerobic and anaerobic organisms. Across the broader Rubisco protein family, homologs exhibit diverse biochemical characteristics and metabolic functions, but the evolutionary origins of this diversity are unclear. Evidence of the timing of Rubisco family emergence and diversification of its different forms has been obscured by a meager paleontological record of early Earth biota, their subcellular physiology and metabolic components. Here, we use computational models to reconstruct a Rubisco family phylogenetic tree, ancestral amino acid sequences at branching points on the tree, and protein structures for several key ancestors. Analysis of historic substitutions with respect to their structural locations shows that there were distinct periods of amino acid substitution enrichment above background levels near and within its oxygen-sensitive active site and subunit interfaces over the divergence between Form III (associated with anoxia) and Form I (associated with oxia) groups in its evolutionary history. One possible interpretation is that these periods of substitutional enrichment are coincident with oxidative stress exerted by the rise of oxygenic photosynthesis in the Precambrian era. Our interpretation implies that the periods of Rubisco substitutional enrichment inferred near the transition from anaerobic Form III to aerobic Form I ancestral sequences predate the acquisition of Rubisco by fully derived cyanobacterial (i.e., dual photosystem-bearing, oxygen-evolving) clades. The partitioning of extant lineages at high clade levels within our Rubisco phylogeny indicates that horizontal transfer of Rubisco is a relatively infrequent event. Therefore, it is possible that the mutational enrichment periods between the Form III and Form I common ancestral sequences correspond to the adaptation of key oxygen-sensitive components of Rubisco prior to, or coincident with, the Great Oxidation Event.

  • Kacar B, Ge X, Sanyal S, Gaucher EA (2017) Experimental Evolution of Escherichia coli Harboring an Ancient Translation Protein. Journal of molecular evolution 84((2-3)):69-84 PMC5371648 · Pubmed · DOI

    The ability to design synthetic genes and engineer biological systems at the genome scale opens new means by which to characterize phenotypic states and the responses of biological systems to perturbations. One emerging method involves inserting artificial genes into bacterial genomes and examining how the genome and its new genes adapt to each other. Here we report the development and implementation of a modified approach to this method, in which phylogenetically inferred genes are inserted into a microbial genome, and laboratory evolution is then used to examine the adaptive potential of the resulting hybrid genome. Specifically, we engineered an approximately 700-million-year-old inferred ancestral variant of tufB, an essential gene encoding elongation factor Tu, and inserted it in a modern Escherichia coli genome in place of the native tufB gene. While the ancient homolog was not lethal to the cell, it did cause a twofold decrease in organismal fitness, mainly due to reduced protein dosage. We subsequently evolved replicate hybrid bacterial populations for 2000 generations in the laboratory and examined the adaptive response via fitness assays, whole genome sequencing, proteomics, and biochemical assays. Hybrid lineages exhibit a general adaptive strategy in which the fitness cost of the ancient gene was ameliorated in part by upregulation of protein production. Our results suggest that an ancient-modern recombinant method may pave the way for the synthesis of organisms that exhibit ancient phenotypes, and that laboratory evolution of these organisms may prove useful in elucidating insights into historical adaptive processes.

  • Domagal-Goldman SD, Wright KE, Adamala K, Arina de la Rubia L, Bond J, Dartnell LR, Goldman AD, Lynch K, Naud ME, Paulino-Lima IG, Singer K, Walther-Antonio M, Abrevaya XC, Anderson R, Arney G, Atri D, Azúa-Bustos A, Bowman JS, Brazelton WJ, Brennecka GA, Carns R, Chopra A, Colangelo-Lillis J, Crockett CJ, DeMarines J, Frank EA, Frantz C, de la Fuente E, Galante D, Glass J, Gleeson D, Glein CR, Goldblatt C, Horak R, Horodyskyj L, Kaçar B, Kereszturi A, Knowles E, Mayeur P, McGlynn S, Miguel Y, Montgomery M, Neish C, Noack L, Rugheimer S, Stüeken EE, Tamez-Hidalgo P, Imari Walker S, Wong T (2016) The Astrobiology Primer v2.0. Astrobiology 16((8)):561-653 PMC5008114 · Pubmed · DOI

    No abstract available.

  • Kaçar B, Gaucher EA (2013) Experimental evolution of protein-protein interaction networks. The Biochemical journal 453((3)):311-9 PMC3727214 · Pubmed · DOI

    The modern synthesis of evolutionary theory and genetics has enabled us to discover underlying molecular mechanisms of organismal evolution. We know that in order to maximize an organism's fitness in a particular environment, individual interactions among components of protein and nucleic acid networks need to be optimized by natural selection, or sometimes through random processes, as the organism responds to changes and/or challenges in the environment. Despite the significant role of molecular networks in determining an organism's adaptation to its environment, we still do not know how such inter- and intra-molecular interactions within networks change over time and contribute to an organism's evolvability while maintaining overall network functions. One way to address this challenge is to identify connections between molecular networks and their host organisms, to manipulate these connections, and then attempt to understand how such perturbations influence molecular dynamics of the network and thus influence evolutionary paths and organismal fitness. In the present review, we discuss how integrating evolutionary history with experimental systems that combine tools drawn from molecular evolution, synthetic biology and biochemistry allow us to identify the underlying mechanisms of organismal evolution, particularly from the perspective of protein interaction networks.