Systems genomics analysis centered on epigenetic inheritance supports development of a unified theory of biology

Abstract

New discoveries are increasingly demanding integration of epigenetics, molecular biology, genomic networks and physiology with evolution. This article provides a proof of concept for evolutionary transgenerational systems biology, proposed recently in the context of epigenetic inheritance in mammals. Gene set enrichment analysis of available genome-level mammalian data presented here seem consistent with the concept that: (1) heritable information about environmental effects in somatic cells is communicated to the germline by circulating microRNAs (miRNAs) or other RNAs released in physiological fluids; (2) epigenetic factors including miRNA-like small RNAs, DNA methylation and histone modifications are propagated across generations via gene networks; and (3) inherited epigenetic variations in the form of methylated cytosines are fixed in the population as thymines over the evolutionary time course. The analysis supports integration of physiology and epigenetics with inheritance and evolution. This may catalyze efforts to develop a unified theory of biology.

Flubendiamide induces transgenerational compound eye alterations in Drosophila melanogaster

“…Three hypotheses might be forwarded for transgenerational transmission of the altered phenotype in Flubendiamide treated fruit flies, 1) it might be due to the effect of the chemical on reproductive organs of P-generation flies, as reported by Yiamouyiannis ( 1983 ), Huang et al ( 1995 ) at different treatment occasions, or 2) it may be autosomal / extra-chromosomal / mitochondrial / cellular inheritance as discussed by Xing et al ( 2007 ) in case of trans-generational transfer of tumor factors in D. melanogaster, or 3) epigenetic factors like microRNAs (miRNAs), DNA methylation, and histone modification might play a distinct role in genetic inheritance and evolution, as suggested by Sharma ( 2015 ).…”

Transcriptomic data reanalysis allows for a contribution of embryonic transcriptional change-induced gene expression reprogramming in transgenerational epigenetic inheritance

“…Besides tRFs, these studies, as also others reporting recently epigenetic inheritance through the male line [ 5–7 ], also found altered levels of various small noncoding RNAs including let-7 miRNAs in sperm. Interestingly, a role of miRNAs, specifically let-7 species, in epigenetic inheritance was predicted previously on the basis of a bioinformatic analysis [ 8 ] that tested the concept [ 9–11 ] that small RNAs transfer heritable information from soma to germline and mediate transmission of environmental effects across generations through gene networks. Emerging evidence [ 1 , 4–7 ] seems consistent with this model.…”

Exosome Carrier Effects; Resistance to Digestion in Phagolysosomes May Assist Transfers to Targeted Cells; II Transfers of miRNAs Are Better Analyzed via Systems Approach as They Do Not Fit Conventional Reductionist Stoichiometric Concepts

“…Systems biology would hold that exosome transfers of miRNA functions are composed of inseparable complex interacting components that we posit are significantly guided by exosome carrier effects. Such an analysis involves the inter-disciplinary study of complex interactions within a such a diverse biologic system, using a new holistic approach to identify processes and not merely just the participating components [ 140 , 141 , 142 , 143 ]. A significant dynamic kinetic influence on all the above arguments concerning carrier effects on the exosome mediated transfers of miRNAs is that the involved exosomes likely bind to the target cell surface over time and then can similarly act dynamically in the intracellular processes [ 52 ].…”