- Assistant Professor, Molecular and Cellular Biology
- Assistant Professor, Astronomy
Betul Kacar is an Assistant Professor in the Molecular and Cellular Biology and Astronomy Departments at the University of Arizona. She received her PhD from the Departments of Chemistry and Biochemistry at Emory Medical School, studying the structure–function relationship of monoamine oxidases. She was a NASA Postdoctoral Fellow of the NASA Astrobiology Institute and a Research Group Leader at Harvard University Department of Organismic and Evolutionary Biology before joining Arizona in 2017 where she focused on reconstructing key enzymatic intermediates between biological activity and global geochemical reservoirs throughout the Earth's deep history through molecular evolution, biochemistry and genomics. The overall goal of Betul's research group is to assess the possible environmental impacts of ancient enzymes on global-scale signatures that record biological activity.
Betul Kacar serves as a Co-PI on NASA Astrobiology Institute's Reliving the Past (CAN7) node. She is an Associate-PI with the Earth-Life Science Institute (ELSI) at Tokyo Institute of Technology and one of the founders of the first and only online astrobiology network SAGANet (saganet.org).
astrobiology, molecular biology, evolution
astrobiology, molecular evolution
Introduction to ResearchMCB 795A (Spring 2018)
- Kacar, B., Garmendia, E., Tuncbag, N., Andersson, D. I., & Hughes, D. (2017). Functional Constraints on Replacing an Essential Gene with Its Ancient and Modern Homologs. mBio, 8(4).More infoGenes 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.IMPORTANCE 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 tuf 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 tuf 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 E. coli tuf 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., 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).More infoTwo 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'.