Mobile elements: Hidden architects of the genome

In 1951, Nobel prize winner Barbara McClintock discovered the first mobile elements in maize. During the 1950s, McClintock built upon her work and reported her findings to the wider scientific community. At this time, little was known about these mobile genetic elements and so many researchers dismissed and ignored them until the late 1960s-70s when they were discovered again, but this time in bacteria and yeast. A large part of the scientific community regarded regions of the genome populated by repetitive sequences (inclusive of mobile elements) as “junk DNA”. The evolutionary importance of such elements has only been recognised since the beginning of the 21st century. Research since this time has grown with the purpose of understanding their role in the evolution of the genome and by extension the evolution of species across all domains of life. These mobile elements have propagated themselves over a vast molecular map that comprises the family tree connecting all life on Earth; from plants, fungi, bacteria, to mammals including humans. Although these elements do not code for what are deemed the most important regions of DNA; used to generate proteins for constituting and maintaining an organism, they constitute a large proportion of the genomes of certain plant and mammalian species. In humans, 1.5% of DNA is comprised of a proposed 20,000 -25,000 protein-coding sequences. Nearly 26% is comprised of non-coding DNA and the remaining 45% composed of transposable elements. Professor Ohshima focuses his research on elucidating the evolutionary journey of these mobile elements, relationships between mobile element families, their mechanisms of intra and inter genome movements and future uses in academic and medical research.

Jumping Genes
Mobile elements or transposons are so named because of their ability to move. They are pieces of genetic sequence that can move about the genetic landscape and target for themselves a new location. There are two classes of mobile genetic elements; determined by the way they move from one genetic location to another. Class I elements use a ribonucleic acid (RNA) intermediate to transpose from one location to another. RNA is an important molecule found in cells that acts as a mediator of cellular communication from DNA to protein production. Without RNA, important proteins cannot be produced that are vital for cellular and at large, whole organism functioning. Class I elements include long terminal repeat (LTR) retrotransposons, endogenous retroviruses, long interspersed elements (LINEs), short interspersed elements (SINEs) and non-autonomous elements known as processed pseudogenes (PPs). Class II elements move or transpose directly from one area of DNA to another without the need of an RNA intermediate. Elements that move in this fashion include DNA transposons and miniature inverted-repeat transposable elements. These elements by what is described as a simple “cut and paste” method. Active class II elements encode an enzyme called transposase which allows the element to move or “jump” to the new site. For both class I and class II elements, upon integration into a new genomic site, duplications of sequence at these target sites can occur. The length of these target site duplications (TSDs) are often characteristic of a particular mobile element.

Mobile elements have propagated themselves over a vast molecular map that comprises the family tree connecting all life on Earth.

Reading between the LINEs
In humans, LINEs and SINEs comprise over 30% of the genome; a large amount compared with other transposable elements. Both SINEs and LINEs use a copy and paste method to insert themselves into another area of the genome. SINEs are non-autonomous and are characterised by a certain type of RNA sequence. One of the most famous SINEs called the Alu element is derived from 7SL RNA in the human genome. In other species of plants and animals, SINEs are known to consist of “head” (originating from tRNA), body and “tail” (LINE origin). During the process of protein synthesis, tRNA is responsible for delivering building blocks called amino acids to a complex molecular machine called ribosome in order to build a sequence of amino acids that then forms a protein in the cell. The tRNA-derived SINE head DNA drives the production of full-length SINE “replicas” (RNA). This means that the SINE element can be subject to multiple rounds of transposition. Professor Ohshima highlights the finding that SINEs possess common genetic sequences of homology with LINEs present at their “tail” end in plants and animals. In one study, Professor Ohshima found that the last 100 nucleotide bases of tobacco TS SINE to be nearly identical with a LINE found in the genome of the same Solanaceae plant. LINE-encoded protein is known to specifically recognise the sequence near the tail end of the LINE RNA to start “copy and paste”, the homology between SINEs and LINEs suggests that each SINE element recruits the enzymatic machinery for transposition from the corresponding LINE through this common tail. Professor Ohshima and colleagues also discovered other LINE/SINE pairs within the turtle (chelonian) and salmonid genomes sharing homologous tail sequences.

Parasites or mutualistic symbionts?
Professor Ohshima and his research team have previously characterised a type of SINE called CHR-1 SINEs present in cetaceans, ruminants and hippopotamuses. One member of this SINE integrated into a coding region of bovine messenger RNA (mRNA). This mRNA/SINE chimera is translated into a protein product that plays a critical role in signal transduction involving control of neurotransmitter release.

In humans, LINEs and SINEs comprise over 30% of the genome; a large amount compared with other transposable elements.

In other studies, Professor Ohshima and colleagues discovered a simultaneous burst of a type of SINE (Alu element) and PP formation in the genome of ancestral primates at approximately 40-50 million years ago. The finding suggests that the explosion of mobile elements at this time along with a change in the structure of the genome may have contributed to the radiation of higher primates. In a recent study by Ms Nishiyama and Professor Ohshima, they discovered definitively that Au SINEs in the genomes of flowering plants shared TSDs located in LINEs of a particular group or clade called RTE.

In recent studies, RTE-clade LINEs have been found to undergo frequent horizontal transfer (HT). This is in opposition to a common understanding of the “vertical” transfer of these gypsies of the genome from one generation to the next within a particular species lineage. This HT involves the movement of genetic information along with a caravansary of mobile genetic elements between different species. Ms Nishiyama and Professor Ohshima propose that a unique motif sequence within the tail end of RTE-clade LINEs allows them to target a similar motif sequence within new host genomes. This may allow them to travel between genomes of different species. Professor Ohshima and his team of researchers are leading the way in elucidating the mechanisms underlying mobile element movement within and between species. Knowledge of the mechanisms of mobile element movement will advance research in gene editing for medical treatment and provide a new insight into the evolution of species through symbiosis between host and mobile element genomes.

References

• Ohshima, K. (2013). ‘RNA-Mediated Gene Duplication and Retroposons: Retrogenes, LINEs, SINEs, and Sequence Specificity’. International Journal of Evolutionary Biology, 2013: 1-16. https://doi.org/10.1155/2013/424726.
• Ohshima K, Okada N. (2005). ‘SINEs and LINEs: symbionts of eukaryotic genomes with a common tail’. Cytogenet Genome Res, 110: 475-490.
• Kazazian jr, H.H. (2004). ‘Mobile Elements: Drivers of Genome Evolution’. SCIENCE, 303: 1626-1632.
• Nishiyama E, Ohshima K. (2018). ‘Cross-Kingdom Commonality of a Novel Insertion Signature of RTE-Related Short Retroposons’. Genome Biol Evol, 10, 6: 1471-1483. doi: 10.1093/gbe/evy098.

Mobile elements: Hidden architects of the Genome