August 18, 2022

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So-Called “Junk” DNA Is Essential, Plays a Key Role in Speciation

Credit: MIT

More than 10 p.c of our genome is made up of repetitive, seemingly nonsensical stretches of genetic materials referred to as satellite tv for pc DNA that do not code for any proteins. In the previous, some scientists have referred to this DNA as “genomic junk.”

Over a collection of papers spanning a number of years, nevertheless, Whitehead Institute Member Yukiko Yamashita and colleagues have made the case that satellite tv for pc DNA will not be junk, however as an alternative has a vital function within the cell: it really works with mobile proteins to maintain all of a cell’s particular person chromosomes collectively in a single nucleus.

Now, within the newest installment of their work, printed on-line July 24 within the journal Molecular Biology and Evolution, Yamashita and former postdoctoral fellow Madhav Jagannathan, at the moment an assistant professor at ETH Zurich, Switzerland, take these research a step additional, proposing that the system of chromosomal group made attainable by satellite tv for pc DNA is one motive that organisms from totally different species can’t produce viable offspring.

“Seven or eight years ago when we decided we wanted to study satellite DNA, we had zero plans to study evolution,” mentioned Yamashita, who can also be a professor of biology on the Massachusetts Institute of Technology and an investigator with the Howard Hughes Medical Institute. “This is one very fun part of doing science: when you don’t have a preconceived idea, and you just follow the lead until you bump into something completely unexpected.”

The origin of species: DNA version 

Researchers have identified for years that satellite tv for pc DNA is very variable between species. “If you look at the chimpanzee genome and the human genome, the protein coding regions are, like, 98 percent, 99 percent identical,” she says. “But the junk DNA part is very, very different.”

“These are about the most rapidly evolving sequences in the genome, but the prior perspective has been, ‘Well, these are junk sequences, who cares if your junk is different from mine?’” mentioned Jagannathan.

But as they had been investigating the significance of satellite tv for pc DNA for fertility and survival in pure species, Yamashita and Jagannathan had their first trace that these repetitive sequences would possibly play a job in speciation.

When the researchers deleted a protein referred to as Prod that binds to a particular satellite tv for pc DNA sequence within the fruit fly Drosophila melanogaster, the flies’ chromosomes scattered exterior of the nucleus into tiny globs of mobile materials referred to as micronuclei, and the flies died. “But we realized at this point that this [piece of] satellite DNA that was bound by the Prod protein was completely missing in the nearest relatives of Drosophila melanogaster,” Jagannathan mentioned. “It completely doesn’t exist. So that’s an interesting little problem.”

If that piece of satellite tv for pc DNA was important for survival in a single species however lacking from one other, it might suggest that the 2 species of flies had advanced totally different satellite tv for pc DNA sequences for a similar function over time.  And since satellite tv for pc DNA performed a job in conserving all of the chromosomes collectively, Yamashita and Jagannathan puzzled whether or not these advanced variations could possibly be one motive totally different species are reproductively incompatible.

“After we realized the function [of satellite DNA in the cell], the fact that satellite DNA is quite different between species really hit like lightning,” Yamashita mentioned. “All of a sudden, it became a completely different investigation.”

A story of two fruit fly species

To examine how satellite tv for pc DNA variations would possibly underlie reproductive incompatibility, the researchers determined to give attention to two branches of the fruit fly household tree: the traditional lab mannequin Drosophila melanogaster, and its closest relative, Drosophila simulans. These two species diverged from one another two to a few million years in the past.

Researchers can breed a Drosophila melanogaster feminine to a Drosophila simulans male, “but [the cross] generates very unhappy offspring,” Yamashita mentioned. “Either they’re sterile or they die.”

Yamashita and Jagannathan bred the flies collectively, then studied the tissues of the offspring to see what was main these “unhappy” hybrids to drop like flies. Right away they observed one thing fascinating: “When we looked at those hybrid tissues, it was very clear that their phenotype was exactly the same as if you had disrupted the satellite DNA [-mediated chromosomal organization] of a pure species,” Yamashita mentioned. “The chromosomes were scattered, and not encapsulated in a single nucleus.”

Furthermore, the researchers might create a wholesome hybrid fly by mutating sure genes within the mother or father flies referred to as “hybrid incompatibility genes,” which have been proven to localize to satellite tv for pc DNA within the cells of pure species.  Via these experiments, the researchers had been capable of exhibit how these genes have an effect on chromosomal packaging in hybrids, and pinpoint the mobile phenotypes related to them for the primary time. “I think for me, that is probably the most critical part of this paper,” Jagannathan mentioned.

Taken collectively, these findings recommend that as a result of satellite tv for pc DNA mutates comparatively incessantly, the proteins that bind the satellite tv for pc DNA and hold chromosomes collectively should evolve to maintain up, main every species to develop their very own “strategy” for working with the satellite tv for pc DNA. When two organisms with totally different methods interbreed, a conflict happens, main the chromosomes to scatter exterior of the nucleus.

In future research, Yamashita and Jagannathan hope to place their mannequin to the final word take a look at: if they will design a protein that may bind the satellite tv for pc DNA of two totally different species and maintain the chromosomes collectively, they may theoretically ‘rescue’ a doomed hybrid, permitting it to outlive and produce viable offspring.

This feat of bioengineering is probably going years off. “Right now it’s just a pure conceptual thing,” Yamashita mentioned. “In doing this tinkering, there’s probably a lot of specifics that will have to be solved.”

For now, the researchers plan to proceed investigating the roles of satellite tv for pc DNA within the cell, armed with their new data of the half it performs in speciation. “To me, the surprising part of this paper is that our hypothesis was correct,” Jagannathan mentioned. “I mean, in retrospect, there are so many ways things could have been inconsistent with what we hypothesized, so it’s kind of amazing that we’ve sort of been able to chart a clear path from start to finish.”

Reference: ” Defective Satellite DNA Clustering into Chromocenters Underlies Hybrid Incompatibility in Drosophila” by Madhav Jagannathan and Yukiko M Yamashita, 24 July 2021, Molecular Biology and Evolution.
DOI: 10.1093/molbev/msab221

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