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Why Are Some Genes Selfish?

We like to think of a healthy organism as a smoothly running machine. A whole made up of intricately related parts. Right down to the cellular level—and inside each cell itself—every element with its role, every function contributing to the good of the whole.

But in fact, if you look deeply enough into living cells, you’re likely to find a whole lot of chaos.

That chaos is something Rochester biologist Jack Werren observed firsthand in the 1980s. While studying entomology at the Walter Reed Institute of Research, he and a colleague discovered a bacteria that altered the sex ratios of insects by killing a large portion of the male offspring, leaving mostly females.

“There is a whole class of inherited elements that alter the reproduction of insects in ways that are beneficial only to the element itself, mostly by altering sex ratios,” says Werren, the Nathaniel & Helen Wisch Professor of Biology.

In 1988, Werren and his Rochester colleagues Uzi Nur and Chung-I Wu brought the diverse discoveries together, formally defining DNA parasites and junk DNA as “selfish genetic elements” (SGEs), an umbrella term for elements that share a common feature: they seek only to enhance their transmission to the next generation and are either harmful or neutral to an organism.

Today Werren is one of a group of researchers in the University’s biology department studying SGEs and their impact on evolution.

“The University of Rochester has one of the highest concentrations of researchers working on selfish genetic elements in North America, if not the world,” says Arvid Agren, the Wenner-Gren fellow in the department of organismic and evolutionary biology at Harvard University. “For many years members of the department have shaped the field, and they continue to do so.”

Rochester biologists have been instrumental, for example, in discovering just how significant the elements really are. Organisms from corn to fruit flies to humans are littered with them, affecting a myriad of biological processes including speciation, aging, diseases, gene regulation, and even sex itself.

“Something very dramatic has shifted,” says Daven Presgraves, a Dean’s Professor in the Department of Biology at Rochester, who studies the role of SGEs in speciation. SGEs “aren’t just these one offs that you can find here and there. Selfish genetic elements are everywhere. And they’re affecting every generation, all the time.”

Each of the cells in your body share the same sequences of DNA, collectively called your genome. Each of the genes that make up the DNA, however, are coded to activate different sequences of proteins, giving cells various functions It turns out, however, that a good portion of your DNA is not even “yours.” That is, it doesn’t code for anything that makes you, you.

Gregor Mendel’s laws of inheritance dictate that a set of parents should produce offspring at a ratio of 50 percent male and 50 percent female. One way to infer the presence of SGEs is to observe generations of an organism and see if their sex ratios are highly distorted: Does a set of parents have a lot more male offspring than females and vice versa?

This question can be difficult to answer in organisms like humans that do not produce many offspring. “You can think off the top of your head of families that have five or more girls and that can happen randomly,” says Amanda Larracuente, an assistant professor of biology at Rochester, who studies Y chromosomes and blocks of repetitive DNA called satellite DNA.

On the other hand, “if you have a family pedigree that for generations had individuals that consistently produced only female offspring, one possibility is that there is a driver on the X chromosome that kills Y-bearing sperm,” she adds. This phenomenon is well-studied in some fruit fly species.

SGE research is also being applied to synthetic drive systems that could be used to suppress pest populations. Wolbachia, for example, spreads through insect populations by altering reproduction, but it also suppresses some viruses. If a mosquito carries certain strains of Wolbachia, it won’t transmit dengue fever and malaria. Injecting mosquitoes in specific regions with Wolbachia and allowing it to spread through a population can therefore help reduce the spread of disease from mosquitoes to humans.

By better understanding the different types of SGEs, the ways SGEs spread, and how they give rise to steps in evolution, synthetic biologists are better able to weigh the risks and benefits of creating engineered systems.

But, while SGEs are now almost universally accepted as drivers of evolution, there is still more work to be done.

“We’re really only beginning to dig in to understand selfish genetic elements as a phenomenon,” Presgraves says. “We now assume that at any point in transmission, there’s a selfish genetic element looking for a way to exploit the transmission. That’s how pervasive selfish genetic elements are.”