Research Interests: Evolutionary Systems Biology, Genetics And Molecular Biology, Computational Biology, Comparative Genomics.
Dr. Krishna Swamy is an Assistant Professor at the Division of Biological and Life sciences, Ahmedabad University. He has had an exciting multi-disciplinary trajectory during his career. He holds a Masters in Physics from Pune University. He started his research career in biology at Molecular Biophysics Unit, IISc, where he developed algorithms for protein structure and function prediction. He then did his PhD in computational biology at the Institute of Information Science, Academia Sinica, Taiwan in 2012. During his PhD, he developed methods to quantify the influence of cellular factors, such as nucleosomes, on the evolution of transcriptional control sequences. He also studied the confluence between sequence evolution and functional evolution of such non-coding sequences in Yeast, Drosophila, and Primates. He transitioned into an experimental biologist at the Institute of Molecular Biology, Academia Sinica, Taiwan after receiving the prestigious Academia Sinica Distinguished Postdoctoral Fellowship, and worked on deciphering the molecular mechanisms underlying speciation, the evolution of complex traits such as fermentation and stress response and evolution of co-operation.
Our lab is interested in combining theoretical and experimental approaches to uncover the general principles underlying the evolution of novel phenotypes, and how these affect the fitness of the organism across various environments. We approach this problem by performing experimental evolution in microorganisms such as E. coli, S. cerevisiae, and hybrids of S. cerevisiae and other related yeasts in a variety of laboratory environments and mathematical modeling. The goal is to identify the key changes in the genetic program that lead to the organism's adaptation to various stresses, and predict from first principles how such mutations can lead to new phenotypes. We are also interested in developing methods to infer the evolutionary history of the emergence of new phenotypes from genomic and transcriptomic data.
Current Research Projects:
Speciation and Hybrid vigor
"Speciation generates discrete populations, which in turn is essential for maintaining novel adaptations during evolution. Hybrids between different species are usually inviable or sterile. Dobzhansky-Muller incompatibilities represent reciprocal-sign epistasis between inter-specific alleles and are widely accepted as a major driver of postzygotic reproductive isolation. They refer to deleterious genetic interactions between functionally diverged loci during evolution of new species. They are widely accepted to cause hybrid sterility or inviability, the features associated with postzygotic reproductive isolation.The evolution of speciation genes is generally thought to be driven by adaptive evolution. Identifying these genes will provide more information about how speciation occurs. One of the main challenges in speciation genetics is that speciation events can normally not be observed and therefore data from present-day species are confronted statistically with competing hypotheses about the genesis of the variation observed, for example in sequences or gene expression. Another paradoxical issue of hybrids is how they can become established in an environment where the parental species also exist. The parental species are expected to be considerably better adapted in their environment relative to hybrids with intermediate genotypes and phenotypes. Hybrids may however contain new gene combinations that contribute new phenotypic characteristics allowing them to exploit other environmental niches not occupied by the parents.
Our lab uses a few closely related yeast species (the Saccharomyces sensu stricto complex) to address these issues. We use classical genetics and molecular biology to identify and dissect the molecular mechanisms of genetic incompatibility, with the aim to determine the common principles underlying speciation. We expose the hybrids to deleterious experimental conditions over many generations to directly investigate genetic change over time. Evolution experiments also help in determining the evolutionary trajectories of stabilization of hybrids."
Evolutionary dynamics of stress response
Most organisms live in dynamic environments, and have to endure a range of different conditions. Often, the set of biological traits needed for the growth and survival of a species can be condition dependent. Correspondingly, organisms have evolved sensory systems to detect and respond to environmental signals, by modification of the expression of biological traits. However, there are limits to the level of phenotypic plasticity in response to changing environments. Environmental shifts can be sudden without preceding signals or signals might be unreliable preparing the organisms for a non existing environmental stress. We use analytical and individual-based models coupled with evolution experiments to investigate the evolution of simple rules that microbes such as E. coli and yeasts to decide whether or not to switch to a protective state, when faced with unreliable signals. We also aim to understand the relationship between heterozygous environments and composition of microbial populations.
Evolution of conflict and cooperation in microbes
Microbes form dense and diverse communities. They are often viewed to form cooperative networks with species producing nutrients and compounds that promote the survival and reproduction of neighboring cells of the same type. They also secrete toxins that can curtail the expansion of other microbes and help capture ecological niche. We develop ecoevolutionary models to study conflict and cooperation in general with a special focus on a form of cooperation that arises through mutual exploitation that is related to cheating and “Black Queen” evolution. Since, cooperation can reduce the productivity of the community and natural selection tend to limit the potential for productive cooperation, we try understand the why cooperation still exist and what is its role evolution of microbial species.
The genome structure of coevolution
*: Co-first author, #: Corresponding author
Swamy KB#, Zhou N, Experimental evolution: its principles and applications in developing stress-tolerant yeasts. Applied Microbiology and Biotechnology, 103(5), 2067-2077, 10.1007/s00253-019-09616-2
Zhou N, Bottagisi S, Katz M, Schacherer J, Friedrich A, Gojkovic Z, Swamy KB, Knecht W, Compagno C, Piškur J. FEMS yeast research. Yeast–bacteria competition induced new metabolic traits through large-scale genomic rearrangements in Lachancea kluyveri. FEMS Yeast Research, Volume 17, Issue 6, https://doi.org/10.1093/femsyr/fox060
Zhou N*#, Swamy KB*#, Leu JY, McDonald MJ, Galafassi S, Compango C, Piskur J. PLOS ONE. Coevolution with bacteria drives the evolution of aerobic fermentation in Lachancea kluyveri, Page no.1-19, doi:10.1371/journal.pone.0173318
Lu YJ, Swamy KB, Leu JY. PLOS Genetics. Experimental Evolution Reveals Interplay between Sch9 and Polyploid Stability in Yeast, Page no 1-26, doi.org/10.1371/journal.pgen.1006409
Majumder P, Chu YJ , Chatterjee B, Swamy,KB, Shen CKJ. Acta Neuropathologica. Co-regulation of mRNA translation by TDP-43 and Fragile X Syndrome protein FMRP, Page no. 1-15, doi:10.1007/s00401-016-1603-8)
Tsai SY, Chang YL, Swamy KB, Chiang RL, Huang DH. Epigenetics & Chromatin. GAGA factor, a positive regulator of global gene expression, modulates transcriptional pausing and organization of upstream nucleosomes, Page no. 1-20, DOI 10.1186/s13072-016-0082-4
MCDonald MJ, Chou CH, SwamyKB, Huang HD, Leu JY. BMC Evolutionary Biology. The evolutionary dynamics of tRNA-gene copy number and codon-use in E. coli. Page no. 1-10 doi: 10.1186/s12862-015-0441-y
Gopinath RK, Yu ST, Swamy KB, Yu JS, Shuyler, SC, Leu, JY. Genome Biology and Evolution. The Hsp90-Dependent Proteome Is Conserved and Enriched for Hub Proteins with High Levels of Protein–Protein Connectivity. Page no. 2851-2865, doi:10.1093/gbe/evu226
Swamy KB, Lin CH, Yen MR, Wang CY, Wang D. BMC Genomics. Examining the condition-specific antisense transcription in S. cerevisiae and S. paradoxus, Page no;1-12, doi:10.1186/1471-2164-15-521
Chiang S*, Swamy KB*, Hsu TW, Tsai ZTY, Lu, HHS, Wang, D, Tsai HK. Gene. Analysis of the association between transcription factor binding site variants and distinct accompanying regulatory motifs in yeast, Page no:237-245, doi.org/10.1016/j.gene.2011.08.028
Swamy KB, Chu WY, Wang CY, Tsai HK, Wang D. BMC Evolutionary Biology. Evidence of association between Nucleosome Occupancy and the Evolution of Transcription Factor Binding Sites in Yeast, page no. 1-10, DOI: 10.1186/1471-2148-11-150
Swamy KB, Cho CY, ChiangS, Tsai ZTY, TsaiHK. Nucleic Acids Research. Impact of DNA-binding position variants on yeast gene expression. Page no. 6991-7001, doi:10.1093/nar/gkp743
Mizutani H, Saraboji K, Malathy SSM, Ponnuswamy MN, Kumarevel T, Swamy KB, Simanshu DK, Murthy MR, Kunishima N. Acta CrystallogarD. Systematic study on crystal-contact engineering of diphthine synthase- influence of mutations at crystal-packing regions on X-ray diffraction quality.
Winter 2019: BPS102 Biophysics (With Dr Ashutosh Kumar and Dr Neha Jain)
Monsoon 2019: CSE106 Basic Programming in Python
FDP102 Environment and Climate Change Studio of the Foundation programme
PhD students and postdocs:
We currently do not have funding to support additional postdocs or PhD students. However, if you are interested in the lab and want to pursue independent funding, please contact Krishna with your CV and brief description of your interest in the lab.
We usually have 1 or 2 masters students who work in the lab. If you are interested in doing research with us, contact Krishna and explain why you want to join the lab.