Context:
For decades, ultra conserved elements have puzzled scientists. DNA pieces having remained essentially unchanged for 80 million years across organisms seem to have a biological constraint so strong that any slight modification would be lethal. But now, with fresh evidence, here is a compelling reason why they are so highly conserved.
What Are Ultra Conserved Elements (UCEs)?
- UCEs are long stretches of identical DNA (>200 bp) in humans, rats, and mice from a common ancestral mammal.
- They have remained remarkably conserved among other species, such as chickens, dogs, and even fishes, implying that there is something vital concerning their biological roles.
- Most UCEs do, in contrast to the majority of genes, not code for proteins; and from that point, their function has mostly remained unknown.
Key Discovery: UCEs Are “Poison Exons”
A functional UCE of the mouse Tra2b gene was shown to actually be a gene serving primarily in RNA splicing by David J. Elliott, at Newcastle.
Working of This UCE
Regulation of Protein Production
- The Splices Tra2 protein is produced by the Tra2b gene and is involved in RNA splicing.
- The present UCE, which functions as a “poison exon,” is found within the first intron of this gene and, when included into the mature mRNA, will otherwise interrupt normal protein production.
- This incorporation is triggered by high abundance of Tra2 protein, with the recognition, and inclusion as an exon, of the UCE.
- The production is then prematurely stopped due to triggering premature stop codons, halting subsequent synthesis of the protein and leading to loss of mRNA.
- Sperm Production Implications
- The mutation in the UCE was deleted in the sperm-producing cells of mice.
- With the absence of the poison exon, a Tra2 protein excess was achieved, causing cell death and infertility.
- Mutations affecting the function of UCEs would then result in those sperm being incapable of forming, and those mutations would not get passed on, thus, UCEs have remained constant throughout evolutionary time.
What Would Keep UCEs Basically Unchanged for 80 Million Years?
- This study supports the idea that UCEs need to remain complete since mutations that knock them out would be strongly selected against.
- Mutations formed in UCEs could meddle with the regulation of proteins and may cause disastrous derangements to cell functions, such as infertility, familiar from Tra2b.
- Hence, the justification why no changes in UCEs were allowed: any mutation would just kill itself before it could be inherited by the next generation.
- Certainly not all UCEs work as poison exons, however, this should provide a useful context for studying their biological relevance in other settings.
Zooming Out: Evolution, Genetics, and Future Exploration
- This research redefines the role of junk DNA by showing that important regulatory functions are often present in non coding regions.
- It demonstrates the precision of control mechanisms, in that a minor regulatory change can translate into major biological changes.
- Beyond that, future exploration might also determine whether other UCEs share in this research, perhaps identifying new regions of function in genetic control.
This represents another major step toward resolving the biggest riddles of evolutionary biology, namely why some DNA sequences are frozen in a time when everything else in the genome is changing.
Source: The Hindu
