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The nematode Halicephalobus mephisto was originally discovered inhabiting a deep terrestrial aquifer 1.3 km underground. H. mephisto can thrive under conditions of abiotic stress including heat and minimal oxygen, where it feeds on a community of both chemolithotrophic and heterotrophic prokaryotes in an unusual ecosystem isolated from the surface biosphere. Here we report the comprehensive genome and transcriptome of this organism, identifying a signature of adaptation: an expanded repertoire of 70 kilodalton heat-shock proteins (Hsp70) and avrRpt2 induced gene 1 (AIG1) proteins. The expanded Hsp70 genes are transcriptionally induced upon growth under heat stress, and we find that positive selection is detectable in several members of this family. We further show that AIG1 may have been acquired by horizontal gene transfer (HGT) from a rhizobial fungus. Over one-third of the genes of H. mephisto are novel, highlighting the divergence of this nematode from other sequenced organisms. This work sheds light on the genomic strategies of adaptation to heat in the first complete subterrestrial eukaryotic genome.

Halicephalobus mephisto was discovered nearly 1.3 kilometers below Earth's surface in the Beatrix Gold Mine of South Africa. When underground, the organism was found to be residing in extreme environmental conditions that could prove to be very strenuous on the organism, such as heated (37 °C), methane-rich, hypoxic water. Genome sequencing of the nematode indicated that there were expansions of the 70 kilodalton heat shock protein (Hsp70) and avrRpt2 -induced genes (AIG1), with both gene families having been previously identified as cellular survival genes. This expansion of both Hsp70 and AIG1 gene families were also found to be convergently expanded in distantly related Mollusks, with expansion specifically present in bivalves. The presence of these convergently expanded gene families within two distantly related animal phylum that both routinely endure environmental stressors such as hypoxia and elevated temperatures can indicate a biosignature response to environmental stress. However, to identify if the unique gene family expansion is truly a biosignature of environmental stress, the survival of the organism must be tested with the inactivation of the expanded gene families. In this work we are exploring the function of these genes, starting with a proposed master regulator gene: ARMET/MANF (Arginine-Rich Mutated in Early State Tumors / Mesencephalic Astrocyte Derived Neurotrophic Factor). RNA interference will allow the inactivation of suspected intermediate regulator proteins such as ARMET, which could then cause a change in either AIG1 or Hsp70 expression and ultimately lead to organismal impairment or death.

Cardiovascular disease (CVD) is the number one cause of death globally, and new therapeutic techniques outside of traditional pharmaceutical and surgical interventions are currently being developed. At the forefront is stem cell-centered therapy, with adipose derived stem cells (ADSCs), an adult stem population, providing significant clinical promise. When introduced into damaged heart tissue, ADSCs promote cardiac regeneration by a variety of mechanisms including differentiation into new cardiomyocytes and secretion of paracrine factors acting on endogenous cardiac cells. We discuss the application of ADSCs, their biochemical capabilities, availability, ease of extraction, clinical trial results, and areas of concern. The multipotent capacity of ADSCs along with their ability to secrete factors promoting cell survival and regeneration, along with their immunosuppressive capacity, make them an extremely promising approach in the field of CVD therapy.

In this study we report a naturally evolved temperature-sensing electrical regulator in the cytochrome c oxidase of the Devil Worm, Halicephalobus mephisto . This extremophile metazoan was isolated 1.3 km underground in a South African goldmine, where it adapted to heat and potentially to hypoxia, making its mitochondrial sequence a likely target of adaptational change. We obtained the full mitochondrial genome sequence of this organism, and show through dN/dS analysis statistically robust evidence of positive selection in H. mephisto cytochrome c oxidase subunits. Seventeen of these positively-selected amino acid substitutions were localized in proximity to the H- and K-pathway proton channels of the complex. Surprisingly, the H. mephisto cytochrome c oxidase proton pump completely shuts down at low temperatures (20°C) leading to approximately a 4.8-fold reduction in the transmembrane proton gradient voltage (ΔΨ m ) compared to optimal temperature (37°C). Direct measurement of oxygen consumption found a corresponding 4.7-fold drop at 20°C compared to 37°C. Correspondingly, the lifecycle of H. mephisto takes four-fold longer at the low temperature compared to higher. This elegant evolutionary adaptation creates a finely-tuned mitochondrial temperature sensor, allowing this ectothermic organism to maximize its reproductive success in varying environmental temperatures. Our study shows that evolutionary innovation may remodel core metabolism to make it more accurately map onto environmental variation., Competing Interests: Competing interests: Authors declare that they have no competing interests.