Molecular mechanisms of adaptation to high hydrostatic pressure

Abstract

The effect of pressure on the thermodynamic stability of biological macromolecules is directly related to the molecules’ change in volume upon denaturation. This suggest that if a macromolecule such as a protein, upon transition from its native state to its unfolded state, experiences a volume change then it is susceptible to the effects of pressure; however, pressure effects can be stabilizing or destabilizing and the sign of the volume change determines which effect will be imparted onto the molecule. If the sign of the volume change is negative (meaning that the native state has a larger volume than the unfolded state) then high pressure will denature the molecule. However, if the sign is positive (meaning that the native state has a smaller volume than the unfolded state) then the molecule will be stabilized by high pressure. This phenomenon can also be applied any two-state biological process such as oligomerization, ligand-binding, complex formation, and even enzymatic reactions, which experience a change in volume upon transition. In the case of these quaternary interactions, if the associated complex has a larger volume than the sum of the volume of the dissociated components, then high pressure will destabilize the complex; however, if the opposite is true (the complex has a smaller volume than the sum of its components) then high pressure will stabilize complex formation. Based on this thermodynamic description of the effect of pressure on biological macromolecules, we set out to understand if piezophilic organisms, when compared to non-piezophilic organisms, may have altered the volumetric properties of their macromolecules and macromolecular complexes in order to withstand the denaturing effects of high hydrostatic pressure.

Single celled organisms represent the dominant form of life on earth. As such, the vast majority of them live under increased hydrostatic pressure. Examples of high-pressure environments include the oceans, below the ocean floor, terrestrial subsurface, caves, and aquifers, to name a few. Recent sampling and sequencing efforts have revealed the incredible biodiversity that inhabits these environments and have even led to the discovery of novel species. Because the vast majority of them have not been cultured, bioinformatics methods have been key in assembling and attributing function to the sequenced genomes. While these studies have elucidated some information on life in extremophilic environments, they are limited in scope as they rely on multiple sequence analyses and homology modelling in order to derive their information. In the studies presented here, we have used both computational and experimental techniques to build upon the knowledge by exploring the thermodynamic mechanisms that may be at play in adaptation to high hydrostatic pressure. Understanding the thermodynamic parameters that govern the stability and activity of organisms and their macromolecules will be key to understanding how organisms have evolved to inhabit extreme environments.