Integrating evolutionarily conserved mechanism of response to radiation for exploring novel Caenorhabditis elegans radiation-responsive genes for estimation of radiation dose associated with spaceflight

Abstract

During space exploration, space radiation is widely recognized as an inescapable perilous stressor, owing to its capacity to induce genomic DNA damage and escalate the likelihood of detrimental health outcomes. Rapid and reliable estimation of space radiation dose holds paramount significance in accurately assessing the health risks associated with spaceflight. However, the identification of space radiation-responsive genes, with their potential to serve as early indicators for diagnosing radiation dose associated with spaceflight, continues to pose a significant challenge. In this study, based on the evolutionarily conserved mechanism of radiation response, an in silico analysis method of homologous comparison was performed to identify the Caenorhabditis elegans orthologues of human radiation-responsive genes with possible roles in the major processes of response to radiation, and thereby to explore the potential C. elegans radiation-responsive genes for evaluating the levels of space radiation exposure. The results showed that there were 60 known C. elegans radiation-responsive genes and 211 C. elegans orthologues of human radiation-responsive genes implicated in the major processes of response to radiation. Through an investigation of all available transcriptomic datasets obtained from space-flown C. elegans, it was observed that the expression levels of the majority of these putative C. elegans radiation-responsive genes identified in this study were notably changed across various spaceflight conditions. Furthermore, this study indicated that within the identified genes, 19 known C. elegans radiation-responsive genes and 40 newly identified C. elegans orthologues of human radiation-responsive genes exhibited a remarkable positive correlation with the duration of spaceflight. Moreover, a noteworthy presence of substantial multi-collinearity among the majority of these identified genes was observed. This observation lends support to the possibility of treating each identified gene as an independent indicator of radiation dose in space. Ultimately, a subset of 15 potential radiation-responsive genes was identified, presenting the most promising indicators for estimation of radiation dose associated with spaceflight in C. elegans.

Keywords: Caenorhabditis elegans; Homologous comparison; In silico analysis; Radiation dose estimation; Radiation-responsive gene; Space radiation.