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The thanatotranscriptome denotes all ribonucleic acid, RNA transcripts produced from the portions of the
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
still active or awakened in the internal organs of a body following its
death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
. It is relevant to the study of the
biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
,
microbiology Microbiology () is the scientific study of microorganisms, those being unicellular (single cell), multicellular (cell colony), or acellular (lacking cells). Microbiology encompasses numerous sub-disciplines including virology, bacteriology, prot ...
, and
biophysics Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations. ...
of
thanatology Thanatology is the scientific study of death and the losses brought about as a result. It investigates the mechanisms and forensic aspects of death, such as bodily changes that accompany death and the postmortem period, as well as wider psychol ...
, in particular within
forensic science Forensic science, also known as criminalistics, is the application of science to criminal and civil laws, mainly—on the criminal side—during criminal investigation, as governed by the legal standards of admissible evidence and criminal ...
. Some genes may continue to be expressed in
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s for up to 48 hours after death, producing new
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
. Certain genes that are generally inhibited since the end of fetal development may be expressed again at this time.


Scientific history

Clues to the existence of a post-mortem transcriptome existed at least since the beginning of the 21st century, but the word ''thanatotranscriptome'' (from (''thanatos-,'' Greek for "death") seems to have been first used in the
scientific literature : ''For a broader class of literature, see Academic publishing.'' Scientific literature comprises scholarly publications that report original empirical and theoretical work in the natural and social sciences. Within an academic field, scient ...
by Javan et al. in 2015, following the introduction of the concept of the human thanatomicrobiome in 2014 at the 66th Annual Meeting of the American Academy of Forensic Sciences in Seattle, Washington. In 2016, researchers at the
University of Washington The University of Washington (UW, simply Washington, or informally U-Dub) is a public research university in Seattle, Washington. Founded in 1861, Washington is one of the oldest universities on the West Coast; it was established in Seattle a ...
confirmed that up to 2 days (48 hours) after the death of mice and zebrafish, many genes still functioned. Changes in the quantities of
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
in the bodies of the dead animals proved that hundreds of genes with very different functions awoke just after death. The researchers detected 548 genes that awoke after death in
zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...
and 515 in
laboratory mice The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory mice are usually of the species ''Mus musculus''. They are the most commonly used ...
. Among these were genes involved in
development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped * Photograph ...
of the organism, including genes that are normally activated only ''
in utero ''In Utero'' is the third and final studio album by American rock band Nirvana. It was released on September 21, 1993, by DGC Records. After breaking into the mainstream with their second album, ''Nevermind'' (1991), Nirvana hired Steve Albini t ...
'' or ''
in ovo IN, In or in may refer to: Places * India (country code IN) * Indiana, United States (postal code IN) * Ingolstadt, Germany (license plate code IN) * In, Russia, a town in the Jewish Autonomous Oblast Businesses and organizations * Inde ...
'' (in the egg) during fetal development. The thanatomicrobiome is characterized by a diverse assortment of microorganisms located in internal organs (brain, heart, liver, and spleen) and blood samples collected after a human dies. It is defined as the microbial community of internal body sites, created by a successional process whereby trillions of microorganisms populate, proliferate, and/or die within the dead body, resulting in temporal modifications in the community composition over time.


Thanatotranscriptomic analysis

Characterization and quantification of the transcriptome in a given "dead" tissue can identify
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
tic assets, which can be used to determine the regulatory mechanisms and set networks of
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
. The techniques commonly used for simultaneously measuring the concentration of a large number of different types of mRNA include
microarrays A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon t ...
and high-throughput sequencing via
RNA-Seq RNA-Seq (named as an abbreviation of RNA sequencing) is a sequencing technique which uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample at a given moment, analyzing the continuously changing c ...
. Analysis from a
serology Serology is the scientific study of Serum (blood), serum and other body fluids. In practice, the term usually refers to the medical diagnosis, diagnostic identification of Antibody, antibodies in the serum. Such antibodies are typically formed in r ...
postmortem can characterize the
transcriptome The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The t ...
of a particular tissue cell type, or compare the transcriptomes between various experimental conditions. Such analysis can be complementary to the analysis of thanatomicrobiome to better understand the process of transformation of the necromass in the hours and days following death.


Applications

Future applications of this information could include: * Constructing a more accurate and nuanced definition of the phenomenon of "
death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
". * Helping
forensic pathologists Forensic science, also known as criminalistics, is the application of science to criminal and civil laws, mainly—on the criminal side—during criminal investigation, as governed by the legal standards of admissible evidence and criminal p ...
(or biologists or veterinarians) establish a more precise time of death (for example, in an eco-health investigation, when the practitioner needs information on the time or cause of poisoning, without a case of
zoonosis A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
). With a better understanding of the steps of this phenomenon in the
human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
thanatomicrobiome, a coroner could, via a ''"postmortem serology",'' establish with greater precision the time since death (by the hour, or even by the minute), which can be useful for investigations to reconstruct the conditions of death. * Illuminating the phenomena of
cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as dis ...
,
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
, and in particular the phenomenon of
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
(including
myocardial Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...
ischemia) and the process of
healing With physical trauma or disease suffered by an organism, healing involves the repairing of damaged tissue(s), organs and the biological system as a whole and resumption of (normal) functioning. Medicine includes the process by which the cells i ...
and resilience, perhaps even for the purpose of facilitating them. The post-mortem gene revival means that, for up to 48 hours following death, enough energy remains in the cells to activate some cellular machinery. At least some of these genes appear to be those involved in physiological healing, or "auto-resuscitation". Previous studies have shown that in people who have died by trauma, heart attack, or suffocation, various genes including those involved in cardiac muscle contraction and wound healing were active more than 12 hours after death. Similar genetic evidence has been found in dental pulp. Some authors in 2015 introduced the concept of ''"thanatotranscriptome
apoptotic Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...
".'' * Understanding
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. It has been found that genes involved in
carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...
are among those reactivated soon after death, with a peak of activity about 24 hours post-mortem. A better understanding of this activity could shed light on the phenomenon of carcinogenesis and potentially lead to new tools to combat it. * Improving the quality of organ transplants. The fact that cancer-related genes are activated following death can shed light on the timing of organ transplantation to reduce the incidence of cancer in transplant recipients.
Liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
transplant recipients have been shown to be more prone to cancers after treatment than would be statistically normal. This phenomenon has been attributed to their post-operative diet, or to the immunosuppressive drugs administered to prevent their body from rejecting the transplant. One hypothesis (yet to be verified) is that post-mortem cancer genes activated in the liver of the
donor A donor in general is a person, organization or government which donates something voluntarily. The term is usually used to represent a form of pure altruism, but is sometimes used when the payment for a service is recognized by all parties as rep ...
may also play a role. * Testing the hypothesis that after death, a rapid decrease of "suppressor gene" activity (which normally inhibit the activation of other genes, including those no longer needed after the fetal stage) would allow dormant genes wake up, at least for a short period of time.


See also

*
Molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
*
Bioinformatics Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...
*
Genevestigator Genevestigator is an application consisting of a gene expression database and tools to analyse the data. It exists in two versions, biomedical and plant, depending on the species of the underlying microarray and RNAseq data. It was started in Janu ...


References

{{Genomics Cell biology Genomics Biophysics Biochemistry Microbiology Death