Rachel O’Neill recently received a $999,999 grant from the NSF. Project Title: Collaborative Research: Impact of a Novel Retrotransposon Expansion on Centromere Function.

Centromeres ensure the correct segregation of chromosomes during cell division and are fundamental to genome evolution. While expansions of DNA within centromeres are known for many species, most centromeres are stable over evolutionary time and are relatively uniform across all centromeres in one genome. Thus, decoupling the equilibration events that occur across chromosomes from the initial seeding events specific to a subset of chromosomes has not been possible in most model systems. This research capitalizes on the recently discovered centromeric expansion of a selfish element, the LAVA retroelement, in a subset of chromosomes in one gibbon genus (Hoolock). Collectively, this funded work will delineate the impact of the organization and function of selfish elements (and conflict) among newly seeded centromeres and stabilized centromeres within one karyotype.

In collaboration with Lucia Carbone, Oregon Health Science Center.

The Tiniest Parasites (an article from UConn Today on work being done in the Gogarten Lab):

salty waters
UConn researchers studied a specific parasitic gene that commonly infects archaea, single-celled microorganisms native to warm, salty waters such as the Dead Sea. Their findings may shed light on how the human genome grew. (iStock Photo)

Bacteria are the smallest organisms that scientists agree are alive. But there are even smaller things that parasitize bacteria. UConn microbiologists have been studying a single gene that is a parasite of bacteria, and in the July 26 issue of the Proceedings of the National Academy of Sciences, they report that while it can hamper individual bacteria, it may help a bacterial population as a whole.

Inteins are parasitic genes that actively invade single-celled organisms, including bacteria, archaea, and yeasts. Once an intein is inside a cell, it deploys a special chemical ‘sword’ that homes in on the cell’s DNA, finds exactly the right spot, and slices it open. Then the intein slips inside and cellular DNA repair machinery stitches the DNA back together as if it was supposed to be there in the first place. The intein doesn’t perform any useful function, at least initially. It just lurks there, getting replicated by the cell’s DNA machinery and passed on when the organism reproduces.

UConn microbiologists Peter Gogarten and Shannon Soucy, a recent Ph.D. in molecular and cell biology, were curious to find out whether inteins took a toll on the host cells they hijack, or whether they provide any benefit.

“You can have a selfish gene, or a domesticated gene. But what happens in between? How does that transition from selfish to domesticated happen?” asks Soucy.

Soucy and Gogarten, along with former UConn undergraduate Anna Green ’13 (CLAS) and colleagues at Tel Aviv University in Israel, decided to look at a specific intein that commonly infects salt-tolerant archaea. The intein is common in salt-tolerant archaea, but not ubiquitous – only 10 percent of salt-tolerant archaea carry it. Which is odd, because one of this intein’s parasitical tricks is super-Mendelian inheritance. It manages to sneak itself into the DNA of its archaea hosts’ offspring about 80 percent of the time. A normal gene’s inheritance rate is 50 percent.

The researchers wondered, if the intein is really so successful at getting inherited, why isn’t it everywhere? Perhaps it is a selfish gene that costs the host, making it less likely to reproduce. But if the intein makes its host less likely to reproduce, why is it still so common?

To figure out why, the researchers decided to break the problem into pieces. First they tried to find out whether the intein actually incurs a cost on the archaea it infects, making them less likely to reproduce.

They created two almost identical strains of Haloferax volcanii, a salt-tolerant archaeon native to warm, salty waters such as the Israeli Mediterranean coast and the Dead Sea. One was infected with the intein, the other was not. And they found that in the laboratory, with plenty of room and resources, the uninfected H. Volcanii without the intein had the advantage and grew about 7 percent faster. Models the researchers made showed that in environments with more limited resources where the archaea couldn’t grow actively, they would still continue to trade genes (archaea, like bacteria, play genetic ‘telephone,’ passing packets of genes around) and after several generations all the archaea would be infected.

The researchers also noticed something else. In these mixed populations, where some archaea were infected with the intein and some were not, the archaea engaged in sexual recombination – in which two archaea fuse, mix up their chromosomes, and then split into two organisms again – more often than they did in intein-free groups. This is obviously good for the intein, as more sexual recombination increases its opportunities to spread. But it’s also good for the archaea, as more recombination leads to faster evolution and a more diverse population that can potentially handle more diverse, and more stressful, environments.

But it still doesn’t explain exactly why, if the intein is so good at getting inherited, and it encourages sexual reproduction, why doesn’t every single salt-tolerant archaeon end up infected within a few generations?

It’s a complicated dynamic, even in the limited ecosystem of a single species’ genome. Gogarten is philosophical about the process.

“Things happen in nature that are not really beneficial for the organism. Humans are full of remnants of genetic invaders we still carry around. Sometimes they pick up a function like the introns [pieces of DNA] that disrupt our genes and have to be removed when the gene is expressed into a protein. Some of these introns have become important in regulation and allow for alternative splicing, increasing the number of different proteins our genome encodes,” he says.

By investigating this smallest of parasites in our smallest of cousins, we might better understand how a few of our ancient enemies, encoded into our genes, became our friends.

August 2, 2016 – Kim Krieger – UConn Communications