Amazing new article in cell Reviews the functions of transposable elements (TEs), and reports a “paradigm shift” against the view that TEs are “junk DNA”. The article “Transposable element DNA and RNA: drivers of gene expression, development, and disease”, begins by noting that TEs “comprise approximately half of mammalian genomes and have shaped genome architecture, chromatin organization, and transcriptional landscapes.” A widely cited statistic (see here or herefor example) says that TEs represent about “45% of the human genome.”
Direct challenge to unwanted DNA
And at the end of the new summary cell The paper directly challenges the view that TEs represent repetitive junk DNA:
TEs can function as alternative promoters, exons, splicing regulators, and tertiary terminal modifiers. They can also act as enhancers, drive three-dimensional (3D) genome organization, and give rise to long non-coding RNAs (lncRNAs) that serve as platforms for transcriptional and chromatin regulators. Mechanistically, TE repression involves DNA methylation, histone modification, phase-separated condensins, RNA modifications, RNA degradation, and nuclear partitioning, yet this repression can be selectively elevated during development or stress to expand regulatory potential. TEs thus contribute to cell type identity, developmental transitions, and responses to environmental stimuli, while their dysregulation is associated with human disorders including neurodegeneration, cancer, and autoimmune diseases. TEs also hold translational promise as biomarkers and tools for gene and cell engineering. In sum, the prevalent integration of TEs as small genes, structural scaffolds, and regulatory elements is redefining our view of the genome: instead of a gene-centric landscape littered with repetitive “junk,” mammalian DNA is a TE-rich ecosystem in which TEs drive gene regulatory networks and their evolution.
Figure 4 of the paper provides a nice diagram listing the multiple functions of TEs. These include:
- Influence on chromatin structure
- Regulation of gene expression
- Acting as silencers for genes
- Act as gene enhancers
- Act as linkage regulators
- It acts as an exon
- Act as alternative promoters
like Another sheet “Most repeats in the human genome are derived from TEs,” he notes, meaning that the functions of TEs have direct effects on the functions of vast amounts of repetitive DNA.
The standard evolutionary view
Of course the paper takes the standard evolutionary view that TEs are formal genetic elements that reproduce randomly and are not meant to exist for any purpose. But it does acknowledge data showing that businesses have “broad and site-specific organizational roles.” Consider this amazing clip:
While initially called “genetic junk,” many TEs have been used (modified) by their hosts and have thus emerged as a force shaping genome structure and gene regulation.
[…]
The story of TEs represents one of the biggest paradigm shifts in modern biology. Once selfish genetic parasites or junk DNA, TEs are now understood as dynamic and essential components of the genome.
[…]
These ideas do not position TEs as passive travelers, but rather as versatile regulatory units, operating at multiple levels of gene regulation. They provide novel chromatin loop stabilizers through CTCF binding, generate enhancer RNAs that stabilize transcriptional networks, donate splice sites that diversify protein isoforms, and give rise to lncRNAs that potentially serve as scaffolds for chromatin modification complexes. In this light, TEs emerge as multidimensional engineers of genomic plasticity, enabling rapid adaptation and innovation across evolutionary and cellular timescales.
The new right outlook
This is a wonderful language coming from cellis often considered the world’s third most important journal for biology (after… nature and sciences). Once again, the study notes that we have witnessed “one of the biggest paradigm shifts in modern biology” away from the view that TEs are “genomic parasites or junk DNA” or that the genome is a “gene-centric landscape dotted with repetitive ‘junk’.” Instead, the new correct view is that “mammalian DNA is a TE-rich ecosystem in which TEs power gene regulatory networks,” and TEs are “essential components of the genome.” Business firms have “broad and location-specific organizational roles.”
Does anyone want to continue to maintain that core elements, and the vast amounts of repetitive DNA they represent, are just functionless junk?
