There are several strategies employed to protect DNA from damage. The spacing between introns is one such structural technique.
Numerous proteins keep a close watch on genomic stability. The class of enzymes known as helicases is exemplary. Helicases are vital to all organisms. Their main role is unpackaging nucleic strands for employment. They also help ensure integrity for their objects of attention.
Not all genomic threats come from without. Some lurk within.
“Transposable genetic elements (TEs) comprise a vast array of DNA sequences, all having the ability to move to new sites in genomes either directly by a cut-and-paste mechanism (transposons) or indirectly through an RNA intermediate (retrotransposons).” ~ Nina Fedoroff
A transposon is a DNA sequence which can change its position within a genome; informally called a “jumping gene.” Transposable elements (TE) were discovered by American cytogeneticist Barbara McClintock in the early 1940s while studying maize.
“Several major types of TE are recognizable in the genomes of a wide range of organisms; these differ in their transposition mechanisms.” ~ English evolutionary biologists Deborah Charlesworth & Brian Charlesworth
In prokaryotes, transposons are essential in cataloging viral encounters, thereupon creating their adaptive immune system (pais) library. Transposons also comprise a large fraction of most eukaryotes’ genomes, as transposition often results in TE duplication. 67% of the human genome comprises transposable elements.
Most TEs are found in intergenic DNA or (to a lesser extent) in introns. In some regions of the genome, TEs can be very densely packed, with jmulitple elements inserted within one another. ~ Deborah Charlesworth & Brian Charlesworth
Transposons are generally considered junk DNA. They have also been characterized as “selfish.” Such blithe dismissal belies biological reality. Depending upon context and instigation, transposons may be beneficial or a bane.
Transposon insertions can have beneficial effects for their respective host organisms. ~ Thomas Eulgem
Transposons help cells adapt to stress and serve as cellular defense against viruses. Insects can quickly become resistant to pesticides thanks to transposons.
Transposable elements can drive evolution by creating genetic and epigenetic variation. ~ Japanese plant cytologist Tokuji Tsuchiya & American plant cytologist Thomas Eulgem
Conversely, these genetic gypsies can disable genes where they impose themselves, even triggering cancer, and contributing to neurodegenerative disorders such as schizophrenia and Alzheimer’s.
Transposons do not just jump. Instead, they usually leave a copy behind at their original location.
If the copy and paste were left unchecked, TEs could explode the genome. But the process is regulated.
After a certain number of copies are made, transposase – the enzyme that catalyzes jumping – reaches a critical threshold, and transposition ceases.
Transposons are not rogue genetic elements. Instead, they are often part of an intricate complex of epigenetic functioning. Transposons associate in families, and the jumps they make transpire through that affiliation. In plants, transposons play a role reprogramming the germline.
The activity of transposons does not only depend on themselves, but also on factors which the host cells produce. ~ Serbian geneticist Ana Marija Jakšic
In a specific adaptation which repeatedly occurred, fish adapted to freshwater from saltwater via transposons.
“A single adaptive genetic innovation repeatedly allowed marine fish to colonize and diversify in freshwater. Transposons were responsible.” ~ American biologist Jesse Weber et al
Transposons orchestrate the genetic expressions responsible for the prolonged pregnancy of placental mammals. This dramatic evolutionary divergence from marsupials transpired ~90 million years ago.
The evolution of pregnancy was associated with a large-scale rewiring of the gene regulatory network. Transposable elements are potent agents of gene regulatory network evolution. ~ American evolutionary biologist Vincent Lynch et al
Though the specifics are not well understood, transposons appear to have played a major role in evolution via cross-species jumps.
“Jumping genes introduce themselves into other genomes.” ~ Australian geneticist David Adelson
Discovered in 2001, piwi-interacting RNA (piRNA) constitutes a huge group of RNA regulatory molecules that keep transposons in check. In humans, piRNA variety may number into the millions. piRNA operate in conjunction with piwi proteins (piwip).
On their own, piwi proteins work to bind or cleave RNA. Piwips are present in both plants and animals.
piRNA-piwi protein complexes (piRNA+piwip) act as a genomic molecular defense system, analogous to an organism’s immune system. Like an adaptive immune system, piRNA+piwip can tell friend from foe, mobilize a response to a jumping gene, and adapt to new TEs. These genomic guardians have a memory of past threats and actions taken, stored epigenetically.
piRNA police track their quarry: they genomically jump just like TEs.
When a transposon migrates, it stands a chance of landing in a piRNA+piwip cluster. When that happens, the TE is captured. piRNA+piwip can recognize a transposon by it never being expressed.
Once entrapped, complementary DNA sequences are produced to thwart the genetic interloper elsewhere, thus gaining protection from that particular TE. In distinguishing between self and uninvited, piRNA+piwip become transposon specific.
piRNA+piwip are prolific. Their variety in mammals may number in the millions.
piRNA are not all-powerful. While they do tackle TEs on their own, piRNA+piwip often enlist help from other RNA management specialists. Genomic protection is a team endeavor.
Some piRNA+piwip do not have transposon targets. Instead, these molecules facilitate cellular learning.
Retrotransposons are a subclass of transposon. They amplify themselves using RNA intermediates, including mRNA. Using RNA intermediates allows rapid copying.
Retrotransposons are ubiquitous in eukaryotes and are particularly abundant in plants, where they may comprise a majority of nuclear DNA. At least 42% of the human genome comprises retrotransposons.
About half of the human genome consists of highly repetitive DNA, what was once considered “junk.” These repetitions are essential to repress retrotransposons and thereby protect the genomic integrity of stem cells.
Methylation is the primary silencing mechanism for retrotransposons in somatic cells. In contrast, stem cell expression is not suppressed by methylation. Chromatin repetitions safeguard stem cells.
We suspect that these viruses are forced to make a choice: either to keep their ‘viral’ essence and spread between animals and species, or to commit to one genome and then spread massively within it. ~ English zoologist Robert Belshaw
Another type of transposon is endogenous retroviruses (ERVs). ERVs are endogenous viral elements that closely resemble retroviruses. Some evolved from retroviruses.
ERVs are a unique combination of pathogen and selfish genetic element. ERVs may replicate either as a transposable element or a virus.
Some ERVs proliferate by infecting germline cells, as typical retroviruses do. Others lack the gene required for virions to enter cells. These behave like retrotransposons.
ERV lineage in eukaryotic organisms is primordial. In evolutionary time, they played an active role in shaping genomes.
ERVs are abundant in jawed vertebrates. ERVs occupy 8–10% of the human genome.
ERVs independently evolved into retrotransposons multiple times. This explains their surfeit in mammal genomes.
The majority of vertebrate ERVs are so ancient as to be inactivated by mutation. Hence, many are merely genetic artifacts in their host.