Tracing the dynamics of gene transcripts after organismal death

Abstract

In life, genetic and epigenetic networks precisely coordinate the expression of genes—but in death, it is not known if gene expression diminishes gradually or abruptly stops or if specific genes and pathways are involved. We studied this by identifying mRNA transcripts that apparently increase in relative abundance after death, assessing their functions, and comparing their abundance profiles through postmortem time in two species, mouse and zebrafish. We found mRNA transcript profiles of 1063 genes became significantly more abundant after death of healthy adult animals in a time series spanning up to 96 h postmortem. Ordination plots revealed non-random patterns in the profiles by time. While most of these transcript levels increased within 0.5 h postmortem, some increased only at 24 and 48 h postmortem. Functional characterization of the most abundant transcripts revealed the following categories: stress, immunity, inflammation, apoptosis, transport, development, epigenetic regulation and cancer. The data suggest a step-wise shutdown occurs in organismal death that is manifested by the apparent increase of certain transcripts with various abundance maxima and durations.

Gene expression in the twilight of death

“…Interestingly, there were qualitative and quantitative differences in degradation profiles and the gene transcripts between the two mouse organs (liver and brain) [2]. Specifically, mRNA increased in the first hour and then gradually decreased in the mouse brain, while mRNA gradually decreased with postmortem time in the mouse liver (see Fig.…”

“…Thousands of postmortem gene transcription profiles from 44 zebrafish (Danio rerio) and 20 house mice (Mus musculus) [2] were produced using the Gene Meter approach. Approximately 99% of gene transcripts decreased in abundance within 30 min of organismal death and continued to decrease with postmortem time.…”

“…Although a rare occurrence ($2%), cancer can originate from pre-existing tumors in the donor organ [44]. Tpr, Csnk2a1]) transcripts in the twilight of death in both organisms (zebrafish and mouse) [2]. Tnfrsf9, Ell] and oncogenic [e.g.…”

“…To frame our essay, we introduce two definitions, organismal death, and "twilight of death"; present the ethical, legal, and medical implications; discuss the methodology used in our recent studies [2,3]; and overview the most important findings we discovered. Only in recent human history has the exact time of a person's death been considered.…”

Complexity of defining death: organismal death does not mean the cessation of all biological life

“…Organismal death occurs well before all of the organism’s parts irreversibly cease vital activity and decompose into inorganic matter. Biological life in some form can and usually does continue after organismal death at least for a time, with recent evidence indicating that animal cell networks continue to perform complex functions like stress response, immune response and inflammation response up to several days postmortem 1. With external support, many cells and tissues can continue to perform their functions ex vivo for long periods of time or even indefinitely 2.…”