Person: Kacar, Betul
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Kacar
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Betul
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Kacar, Betul
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Publication Exoplanet Biosignatures: Future Directions(Mary Ann Liebert, Inc., 2018) Walker, Sara I.; Bains, William; Cronin, Leroy; DasSarma, Shiladitya; Danielache, Sebastian; Domagal-Goldman, Shawn; Kacar, Betul; Kiang, Nancy Y.; Lenardic, Adrian; Reinhard, Christopher T.; Moore, William; Schwieterman, Edward W.; Shkolnik, Evgenya L.; Smith, Harrison B.Abstract 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.Publication Functional Constraints on Replacing an Essential Gene with Its Ancient and Modern Homologs(American Society for Microbiology, 2017) Kacar, Betul; Garmendia, Eva; Tuncbag, Nurcan; Andersson, Dan I.; Hughes, DiarmaidABSTRACT 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 tufA gene in the Escherichia coli genome with its extant and ancestral homologs. The extant homologs represented tuf variants from both near and distant homologous organisms. The ancestral homologs represented phylogenetically resurrected tuf sequences dating from 0.7 to 3.6 billion years ago (bya). Our results demonstrate that all of the foreign tuf genes are transferable to the E. coli genome, provided that an additional copy of the EF-Tu gene, tufB, remains present in the E. coli genome. However, when the tufB gene was removed, only the variants obtained from the gammaproteobacterial family (extant and ancestral) supported growth which demonstrates the limited functional interchangeability of E. coli tuf with its homologs. Relative bacterial fitness correlated with the evolutionary distance of the extant tuf homologs inserted into the E. coli genome. This reduced fitness was associated with reduced levels of EF-Tu and reduced rates of protein synthesis. Increasing the expression of tuf 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.Publication Experimental Evolution of Escherichia coli Harboring an Ancient Translation Protein(Springer US, 2017) Kacar, Betul; Ge, Xueliang; Sanyal, Suparna; Gaucher, Eric A.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. Electronic supplementary material The online version of this article (doi:10.1007/s00239-017-9781-0) contains supplementary material, which is available to authorized users.Publication Resurrecting ancestral genes in bacteria to interpret ancient biosignatures(The Royal Society Publishing, 2017) Kacar, Betul; Guy, Lionel; Smith, Eric; Baross, JohnTwo 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’.Publication The Astrobiology Primer v2.0(Mary Ann Liebert, Inc., 2016) Domagal-Goldman, Shawn D.; Wright, Katherine E.; Adamala, Katarzyna; Arina de la Rubia, Leigh; Bond, Jade; Dartnell, Lewis R.; Goldman, Aaron D.; Lynch, Kennda; Naud, Marie-Eve; Paulino-Lima, Ivan G.; Singer, Kelsi; Walter-Antonio, Marina; Abrevaya, Ximena C.; Anderson, Rika; Arney, Giada; Atri, Dimitra; Azúa-Bustos, Armando; Bowman, Jeff S.; Brazelton, William J.; Brennecka, Gregory A.; Carns, Regina; Chopra, Aditya; Colangelo-Lillis, Jesse; Crockett, Christopher J.; DeMarines, Julia; Frank, Elizabeth A.; Frantz, Carie; de la Fuente, Eduardo; Galante, Douglas; Glass, Jennifer; Gleeson, Damhnait; Glein, Christopher R.; Goldblatt, Colin; Horak, Rachel; Horodyskyj, Lev; Kacar, Betul; Kereszturi, Akos; Knowles, Emily; Mayeur, Paul; McGlynn, Shawn; Miguel, Yamila; Montgomery, Michelle; Neish, Catherine; Noack, Lena; Rugheimer, Sarah; Stüeken, Eva E.; Tamez-Hidalgo, Paulina; Imari Walker, Sara; Wong, Teresa