Foreign Elements And Aberrant Molecules In Biology
Foreign means 'of or belonging to another' and etymologically derives from foris (lat. for 'outside'). This implies that there has to be an inside too and in biology, at first glance, this inside seems easily defined. The inside has to be within the cell or within the genome. But many exogenous elements, such as bacterial or viral pathogens, are found in great numbers within the cell(s) of host organisms and are nevertheless not considered as endogenous or “own”. Similarly, vast amounts of eukaryotic genomes are colonized by transposons, a class of genetic elements with diverse capabilities to move and proliferate within host genomes. These colonizing elements are also widely recognized as foreign genetic elements. Hence, both initial definitions cannot catch the two main classes of foreign elements of biology. In case of transposons, the situation is inevitably more complex as they are themselves components of their hosts genomes. As such they can drive their evolution. Nevertheless, transposable elements (TE), in some instances, are indisputably foreign elements. One of those instances is horizontal transfer between host organisms, a phenomenon that is increasingly recognized as a common driver of evolutionary change and is often connected to a host-pathogen relation between donor and acceptor of the transferred element.
Another way to define foreign genetic elements is by their ability to damage their host. Again, this appears very evident when observing bacterial or viral pathogens, but is a more complex matter when considering transposable elements. On one hand, their action can result in evolutionary advantageous changes of their host genomes, via alterations of gene functions, large scale genome rearrangements, but also as a source of novel coding or regulatory sequence material. Transposons have introduced many remarkable examples of genetic diversity by through molecular domestication. These include many agriculturally important traits, such as the diversity in vine grape coloring or the cold-inducible expression of a gene that drives the anthocyanin biosynthesis in blood oranges.
Coding sequences of TEs have also been co-opted and the most prominent example is found in the appearance of the adaptive immune system of vertebrates. The recombination activating enzymes that catalyze DNA rearrangements in antibody coding sequences are derived from ancient DNA transposons and enable the almost infinite repertoire of specific immune cells. On the other hand, transposable elements carry a vast destructive potential to their host and were, amongst other detrimental effects, linked to a multitude of human diseases. For these reasons they underlie purifying selection. Consequently, all clades of life have evolved epigenetic mechanisms to control the expression and expansion of TEs. These epigenetic marks are potent regulators of the transcriptional landscape and are capable to contain the bulk of TEs. In addition, there is a second layer of control at the post transcriptional level to maintain cellular integrity. It is predominantly exerted through protein folding quality control and RNA quality control (RQC), which can be summarized as the cellular quality control machinery. While protein folding quality control appears to have little effect on the regulation of exogenous elements, RQC has an enormous capability to differentiate self from non-self. It was recently even proposed that the emergence of epigenetic control and RQC were necessities for the rise of transposons within eukaryotic genomes. This epigenetic control has proven to be very successful not only in TE defense, but also in establishing developmental systems that rely on both memory and the ability to restore. Balancing erasure and preservation of epigenetic memory systems therefore harbors a great potential. Quality control mechanisms discriminate between correct and aberrant molecules in biological systems to ensure intact functioning of cellular processes and in doing so, prevent detrimental effects evoked on regular functions within the cell. Aberrant is defined as diverging from the common form and quality control is often considered to eliminate from the molecules emerging from mistakes in cellular processes. As biological systems are very variable, the molecular processes within a cell can change depending on the conditions and environment. Hence, how can the cell distinguish the currently normal and necessary products from aberrant molecules? To understand this within the context of RQC we need to first consider RNA as a molecule.
RNAs can be divided in two major classes. Non-coding RNAs generally serve a structural, catalytic or regulatory function. The vast majority of non-coding RNAs are found as structural backbone of the ribosome, which catalyzes the addition of amino acids to polypeptide chains based on the coding sequences of messenger RNA (mRNA). These coding mRNAs comprise the second class and they share some well-defined characteristics. The extremities of mRNA are marked on the 5’ end by a cap structure and on the 3’ end by a variably long poly(A)-tail. Because these are key features of mRNA, lack thereof is associated with fast sorting and degradation of such mRNA in a process called RQC. Besides those fundamental features, many other characteristics of mRNA are recognized in addition by RQC. However, there is a fine line between what is recognized as aberrant or normal and organisms face great challenges to establish this balance. One example of such balancing is the interplay between RQC and RNA silencing. RNA silencing is a regulatory machinery that relies on specific small RNA to regulate gene expression and has key involvements in developmental regulations. It was also shown to act as very potent immune system against viral pathogens in some clades of life, most notably in plant species.
