Conserved regulation of gluconeogenesis in Haloarchaea

Hypersaline-adapted archaea, or haloarchaea, survive in extreme and fluctuating environments, where daily and seasonal changes in near-saturated salinity, oxygen, and nutrients require rapid regulation of essential cellular processes. Within this group are organisms that can oxidize sugar and organisms that utilize other compounds such as amino acids, gluconate, or pyruvate for aerobic growth. Given the similar environmental pressures experienced by these organisms, how did these two metabolic strategies evolve, and how are they regulated? 

We approached this question by looking at the transcriptional regulation of a conserved protein, TrmB. Sugar-binding TrmB proteins are found in nearly all sequenced haloarchaea, and TrmB is known to upregulate the expression of gluconeogenic genes when sugar is absent in Hbt. salinarum. However. Hbt. salinarum does not rely on glucose to power its metabolism, and we were interested in identifying how the targets of TrmB homologs may have changed in haloarchaeal species that do consume sugars for energy. 

The TrmB regulatory control point of gluconeogenesis has shifted between Hca. hispanica and Hbt. salinarum. 

General Stress Response in Archaea

The environmental stress response (ESR) is a global transcriptional program originally identified in yeast. It is characterized by a rapid and transient transcriptional response composed of large, oppositely regulated gene clusters. Genes induced during the ESR encode core components of stress tolerance, macromolecular repair, and maintenance of homeostasis. We used the largest collection of expression experiments available for an archaeal species, Hbt. salinarum, to explore the existence of a coordinated global transcriptional program in response to stress. We found that Hbt. salinarum exhibits a genome-wide ESR-like response to stress: across ~1500 transcriptome profiles including a variety of conditions, two major clusters emerge. Hbt. salinarum genes induced in response to stress are enriched for the same functions as genes induces in S. cerevisiae ESR. Furthermore, both models display similar recovery dynamics to stress of increasing intensity. 

By recognizing a transcriptional stress response in archaea, we create a framework to begin comparing transcriptomes, with the goal of identifying conserved features of the ESR across archaeal species and across domains of life.  These types of experiments are not limited to genetically tractable archaea. As costs continue to fall for high-throughput sequencing, large-scale comparative studies across related species can be an attractive alternative to genetic manipulations. 

Selected Publications