Genome complexity: role of satellite DNA (Introduction)

by David Turell @, Friday, May 27, 2022, 21:57 (33 days ago) @ David Turell

A newly discovered facet of 'junk' DNA:

"In a new study, biologists at the University of Pennsylvania show, for the first time, evidence of a two-sided genomic arms race involving stretches of repetitive DNA called satellites. "Opposing" the rapidly evolving satellites in the arms race are similarly fast-evolving proteins that bind those satellites.

"While satellite DNA does not encode genes, it can contribute to essential biological functions, such as formation of molecular machines that process and maintain chromosomes. When satellite repeats are improperly regulated, impairments to these crucial processes can result. Such disruptions are hallmarks of cancer and infertility.

"Using two closely related species of fruit flies, researchers probed this arms race by purposefully introducing a species mismatch, pitting, for example, one species' satellite DNA against the other species' satellite-binding protein. Severe impairments to fertility were a result, underscoring evolution's delicate balance, even at the level of a single genome.

"'We typically think of our genome as a cohesive community of elements that make or regulate proteins to build a fertile and viable individual," says Mia Levine, an assistant professor of biology in Penn's School of Arts & Sciences and the senior author on the work, published in Current Biology. "This evokes the idea of a collaboration between our genomic elements, and that's largely true.

"'But some of these elements, we think, actually harm us," she says. "This disquieting idea suggests that there needs to be a mechanism to keep them in check."

"The researchers' findings, likely to also be relevant in humans, suggest that when satellite DNA occasionally escapes the management of satellite-binding proteins, significant costs to fitness can occur, including impacts on molecular pathways required for fertility and perhaps even those relevant in the development of cancer.

"'These findings indicate that there is antagonistic evolution between these elements that can impact these seemingly conserved and essential molecular pathways," says Cara Brand, a postdoc in Levine's lab and first author on the work. "It means that, over evolutionary time, constant innovation is required to maintain the status quo."


""If genes are words and you were to read the story of our genome, these other parts are incoherent," she says. "For a long time, it was ignored as genomic junk."

"Satellite DNA is part of this so-called "junk." In Drosophila melanogaster, the fruit fly species often used as a scientific model organism, satellite repeats make up roughly half the genome. Because they evolve so rapidly without any apparent functional consequence, however, scientists used to believe satellite repeats were unlikely to be doing anything useful in the body.


"In 2001, a group of scientists put forward a theory, suggesting that coevolution was taking place, with the satellites rapidly evolving and satellite binding proteins evolving to keep up. In the two decades since, scientists have offered support to the theory. With genetic manipulation, these studies have introduced a satellite-binding protein from one species into the genome of a closely related species and observed what happens as a result of the mismatch.

"'Often these gene swaps cause dysfunction," says Brand, "particularly disrupting a process that is usually mediated by regions of the genome that are enriched with repetitive DNA."


"Another fruit fly species, Drosophila simulans, lacks a satellite repeat that spans a whopping 11 million nucleotide base pairs found in its close relative, D. melanogaster. This satellite was known to occupy the same cellular location as a protein called Maternal Haploid (MH). The researchers also had access to a mutant strain of D. melanogaster that lack the 11 million base pair repeat.

"'It turns out the fly can live and reproduce just fine without this repeat," Levine says. "So it gave us a unique opportunity to manipulate both sides of the arms race."


"Looking to the closest relative of the MH protein in humans, a protein called Spartan, gave the scientists a clue as to the mechanism behind these results. In humans, Spartan is understood to digest proteins that can get stuck on DNA, posing an obstacle to various processes and packaging that DNA must undergo. "After everything we'd discovered thus far," Levine says, "we thought, maybe this wrong species version of the protein is chewing up something it shouldn't."

"One of the proteins often targeted by Spartan is Topoisomerase II, or Top2, an enzyme that can help resolve tangles in tightly wound and entangled DNA. To see whether the negative effects of the MH gene mismatch owed to inappropriate degradation of Top2, they overexpressed Top2 and found fertility was restored. Reducing Top2, on the other hand, exacerbated the reduction in fertility.

"'This repair process that MH is involved in happens in yeast, in flies, in humans, across the tree of life," says Brand. "Yet we're seeing rapid or adaptive evolution of these proteins involved. That suggests that this seemingly conserved and essential pathway requires evolutionary innovation." In other words, coevolution must proceed apace, just to maintain this essential pathway."

Comment: a complex study revealing another layer of coding controls hidden in the so-called junk

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