Possible Applications of Latest Biological and Medical Trends in Anthropology

Abstract

This brief note highlights the possible, remarkable role that epigenetic and proteomics on the one hand and neurogastroenterology on the other hand, may play in paleoanthropological and paleopathological research.

Epigenetics, Epiproteomics and Paleoanthropology

Epigenetics is the study of heritable phenotypic changes, which arise without changes of genomic sequence, but mainly through environmental influences, which give rise to a variability in the gene expression. The chief molecular mechanisms with which epigenetic phenomena take place, are in the context of reversible covalent chromatin modifications, amongst which are DNA methylations, histone acetylation’s and miRNA (that regulates just gene expression) modifications. Furthermore, epigenetic mutations (above all, DNA methylations), most of which are reversible, have also a greater rate than genetic ones, due to the major sensibility on environmental conditions by the former which stress gene expression [1-4].

Epigenetic transformations account for the differences between primates and humans, which share commonly about 99% of DNA, and has also contributed to domestication of animals. Epigenetic data have shown that above all methylations processes have contributed to phenotypic variations during human evolution, having acted more on gene expression rather than on protein sequences. Nevertheless, if one limits to consider only these outcomes, some incongruities may stand out by the comparison between some primates (like orangutans) and humans. Furthermore, there also exist gene sequences of primates and humans, lying at the protein level, having epigenetic diversities [3-5].

As epigenetics plays a very crucial role in the phenotypic manifestations from the genotype, it is obvious that protein formation – which is more dynamical than gene phenomenologyis closely related to epigenetic mutations. Likewise to genomics, the study of expression, interaction and communication (or information exchange) of all proteins contained into a cell, is said to be proteomics. Moreover, the analogical parallel to the pattern of epigenetics gives rise to the so-called epiproteomics meant as the study of the effects, as consequences, of the influences of environment (posttranslational modifications, in short PTMs) in the protein formation from proteotype (analogous to genotype), which may be heritable as epigenetic marks for those related genomic traits epigenetically influenceable. In particular, we recall that proteins are fundamental for the working of memories, some of which operate just in a similar manner to viral mechanisms [6] as well as they may modify RNA. Early fetal brain development is a highly complex and tightly regulated process. Consequently, small alterations can lead to severe phenotypes such as cortical malformations, epilepsy and intellectual disability. Further, structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid [7,8].

So, to sum up, epigenetics refers to a “heritable” phenomena in which the phenotypic changes are independent of DNA sequence, while epiproteomics is the Post-Translational Modifications (PTMs) that involve histone acetylations, SUMOylations, phosphorylations and ubiquitinations. In turn, the PTMs might regulate various biological processes by means of the modulation of chromosomal structures or regulating the binding of chromatin [9]. Histone methylation is a dynamic process with a key role in development and differentiation. Aberrant levels of histone methylation are likely to play a causal role in tumorigenesis. The outcomes of methylation on histones are highly context dependent and can be associated with different gene expression status. Histone methylation is then intimately associated with transcriptional regulation by influencing chromatin architecture, recruiting transcriptional factors, interacting with initiation and elongation factors, hence affecting RNA processing [10]. The epiproteomics studies therefore all the Post-Translational Modifications (PTMs) regarding the proteins of a cell or organism [11].

However, proteins are amongst the major promoters and regulators of biological processes; their identity and function are defined by the unique sequence of amino acids, which structure them, and may elicit multiple functions on the basis of their interaction with other proteins. Therefore, it is of central interest in biology to determine the interactions and cooperation of proteins (whose set is said to be proteome) as a function of cell state. Thus, protein-protein interactions (whose net is said to be interactome) play an essential role in many biological processes in livings systems; current research indicates too that alterations in the interactome network are relevant for many human diseases including neurodegeneration. Most human diseases involve changes in the composition or functions of proteins in one form or another: for instance, as has already been said, structural and functional brain alterations are also reflected in the protein composition of cerebrospinal fluid.

Proteome stronger depends on environmental influences, is time-dependent and more cell-specific than genome. It is important and useful to define a protein expression pattern as the main outcome of the phenotype, varying by Post-Transcriptional Modifications (PTMs). Functional and expressive proteomics tries to study structure and functions of expressed proteins of a cell or tissue. Proteins are however much more liable to environmental conditions and variations than gene sequences. Furthermore, it is very important to determine, where is possible, protein families, their formation and phylogenetic evolution which seems to play a stronger role than that of genome code, in giving rise families and super-families of proteins [12-14].

It is therefore relevant and fruitful to consider epigenetics and, above all, epiproteomics as applied to paleoanthropology to study human evolution, and vice versa. Indeed, proteomics should be taken into account besides and jointly to epigenetics, in that there exist proteins which are not predictable on the basis of genome sequences only, as well as it is able to consider also that key intercellular signalling closely related with gene expression and cell phenotype. In conclusion, epigenetics and epiproteomics should give valuable insights to paleoanthropological research.

Neurogastroenterology and Paleoanthropology

Gastrointestinal tract is thickly interconnected with brain (braingut connection) through a dense net of nervous fibers such to make it one of the most innervated system of human body. This justifies the name of enteric nervous system (in short, ENS) given to it, also nicknamed ‘‘second brain’’. So, a new medical ambit is born, i.e., the neurogastroenterology [15]. Before the discovery of such a remarkable and crucial link, it is usually thought that a main one-direction way hold between Central Nervous System (CNS) and gut, in the sense ‘‘brain turned gut’’, but not vice versa. Instead, the modern medical and physiological research has pointed out the existence of an interconnection way also in the contrary sense as much important as the first one. Current findings show that bowels illnesses entail as well mood changes and disorders. Neurogastroenterology just focuses on ENS-CNS axis [16]. The latest researches also suggest that digestive system activity may influence even cognition, a valuable correlation this last which was already descried by Freudian psychoanalysis in the psychosexual development of human being, where just anal phase plays a key role in thought processes and in the symbolic function rising for human being. So, neurogastroenterology may provide valuable insights and technical support to Freudian psychoanalysis from a ontophylogenetic perspective, if such an interdisciplinary study to psychoanalysis is performed in cooperation with paleoanthropology and paleopathology insofar soft tissues may be enrolled as paleoanthropological finds; in turn, neurogastroenterology may get new perspectives from a better knowledge of the ENS-CNS connections from an evolutive or phylogenetic standpoint.

References

1. Moore DS. The Developing Genome. An Introduction to Behavioural Epigenetics. Oxford University Press, Oxford, UK. 2015.
2. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nature Reviews Drug Discovery. 2012; 11: 384-400.
3. Dupont C, Armant DR, Brenner CA. Epigenetics: definition, mechanisms and clinical perspectives. Seminars in Reproductive Medicine. 2009; 27: 351-57.
4. Hernando-Herraez I, Prado-Martinez J, Gang P, Fernandez-Callejo M, Heyn H, Hvilsom C, et al. Dynamics of DNA Methylation in Recent Human and Great Ape Evolution. PlosGenetics. 2013.
5. Dickins TE, Rahman Q. The extended evolutionary synthesis and the role of soft inheritance in evolution. Proceedings of the Royal Society, B. Biological Sciences. 2012.
6. Pastuzyn ED, Day CE, Kearns RB, Kyrke-Smith M, Taibi AV, McCormick J, et al. The neuronal gene Arc encodes a repurposed retrotransposon gag protein that mediates intercellular RNA transfer. Cell. 2018; 172: 275-288.
7. Liebler DC. Introduction to Proteomics. Tools for the New Biology. Humana Press, Inc. Totowa, NJ. 2001.
8. Twyman RM. Principles of Proteomics. 2^nd Edition, Garland Science (Taylor & Francis Group), LLC, New York. USA. 2014.
9. Song H, Liu D, Dong S, Zeng L, Wu Z, Zhao P, et al. Epitranscriptomics and epiproteomics in cancer drug resistance: therapeutic implications. Signal Transduction and Targeted Therapy. 2020; 5: 193.
10. Zhao Z, Shilatifard A. Epigenetic modifications of histones in cancer. Genome Biology. 2019; 20: 245.
11. Kaur S, Baldi B, Vuong J, O’Donoghue S. Visualization and Analysis of Epiproteome Dynamics. Journal of Molecular Biology. 2019; 431: 1519-1539.
12. Dorit RL, Gilbert W. The limited universe of exons. Current Opinion in Structural Biology. 1991; 1: 973-977.
13. Dorit RL, Schoenbach L, Gilbert W. Exon shuffling and the underlying motifs of protein evolution. Journal of Cellular Biochemistry. 1991.
14. Tyers M, Mann M. From genomics to proteomics. Nature. 2003; 422: 193- 197.
15. Wood JD, Alpers DH, Andrews PLR. Fundamentals of neurogastroenterology. Gut. 1999; 45: II6-II16.
16. Rao SSC, Lee YY, Ghoshal UC. Clinical and Basic Neurogastroenterology and Motility. Academic Press/Elsevier Inc. London. UK. 2020.