The Evolution of Sex Could Have Provided a Defense Against Cancer Cells

The first sexually reproducing organisms may have found that the energy-intensive enterprise bolstered defenses against malignant cells

A digitally-colorized scanning electron micrograph depiction of a Giardia lamblia protozoan caught in a late stage of cell division, producing a heart-shaped form. Most protozoa, or singled-celled eukaryotes, reproduce asexually, but there is evidence to suggest Giardia lamblia can reproduce sexually as well. ( Media for Medical)
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Why organisms began having sex, rather than simply reproducing asexually as life did for billions of years—and still does, in the case of single-celled organisms and some plants and fungi—is a bit of a mystery. Sexual reproduction evolved around a billion years ago or more, despite the additional energy required and the seeming hinderance of needing to find a suitable mate. Prevailing theories hold that sex became the dominant form of reproduction due to the benefits of greater genetic diversity, allowing offspring to adapt to changing environments and keeping species one step ahead of parasites that evolved to plague the parents.

But in a new paper in PLOS Biology, a team of scientists led by the University of Montpellier in France and Deakin University in Australia suggest another reason life started and kept having sex: the threat of transmissible, cancerous freeloaders.

“We suggest that sexual reproduction evolves to prevent invasion by transmissible selfish neoplastic cheater cells, henceforth referred to as transmissible cancer cells,” Frederic Thomas, an evolutionary biologist at the University of Montpellier and lead author of the study, says in an email. “To our knowledge, this selective scenario for the initial evolution of sex across the tree of life is novel.”

Cancer wasn’t a problem for the earliest life forms, prokaryotes, or single-celled organisms that lack a cell nucleus, such as bacteria and archaea. These creatures reproduce asexually, making a copy of their singular chromosome and essentially cloning themselves.

But things changed with the evolution of eukaryotes more than 2.5 billion years ago. These organisms contain central nuclei encompassing their genomes in a set of chromosomes. Groups of eukaryotes joined together to form the first multicellular organisms—the predecessors of all complex life on Earth, from plants to insects and reptiles to mammals. When these organisms reproduce, genetic material is contributed from two mates, creating genetically unique offspring.

“Sex seems to have accompanied, directly predated or actually marked the transition to eukaryotic life,” says Maurine Neiman, an associate professor of biology at University of Iowa who studies sexual reproduction but was not involved in the new study. The big question in evolutionary biology, she says, is why.

Sex is really complicated and inefficient. Many organisms must invest biological resources in traits that serve the sole purpose of attracting a mate, such as peacock feathers. Even the act of copulation itself carries risk. “Organisms are often literally stuck together, and that’s not really a great situation be in,” Neiman says. The idea that a creature successful enough to reach reproductive maturity would want to mess with the genetic formula is also odd. “You’re kind of a sure thing if you have grown up and been successful. Why would you go and make a baby different from you?”

Eukaryotic Reproduction
By blending genetics, sexual reproduction produces greater genetic diversity in a population, limiting the transmission of cancer cells across individuals in the population. (Thomas et al. / PLOS Biology 10.1371)

One leading theory is known as the Red Queen hypothesis. The idea suggests that as multicellular life evolved, so did the parasites and pathogens that plagued it. By using sex to create offspring with unique genetic traits, some of the offspring may acquire resistances to the bugs that would otherwise threaten entire species. Sexual reproduction serves as a way to stay a step ahead the evolutionary arms race. (The name of the hypothesis comes from a statement by the Red Queen to Alice in Lewis Carroll's Through the Looking-Glass: “Now, here, you see, it takes all the running you can do, to keep in the same place.”)

The new study suggests that cancer cells can be considered another form of parasite. As early cells banded together to form single, eukaryotic organisms, these organisms would have needed to guard against member cells that refused to subordinate themselves to the whole—“internal cheater cells,” or cancer cells. Early multicellular organisms would also have needed to develop defenses against invading malignant cells from other organisms, or transmissible cancers.

Such early immune systems would have had an easier time differentiating between healthy cells and malignancies, the study argues, if sexual reproduction created offspring that were genetically distinct from surrounding organisms. Targeting cancerous cells could have created an evolutionary pressure to embrace sex, similar to the pressure from parasites and other pathogens.

“Malignant cells—at least in our opinion—have the same importance in evolutionary biology and ecology as non-self parasites and therefore should be considered as important as parasites and microbiota,” Thomas says. “Cancer is not only a disease, it is an evolutionary force.”

This idea could be a powerful new way of thinking about evolution, according to Steve Johnson, a biologist studying the evolution of sex and host-parasite interactions at the University of New Orleans. “The more I think about it, I really believe this could be a very important new approach,” he says in an email. “I especially like their linking Red Queen modeling with the idea that sexual reproduction reduces a unique kind of parasite, the transmissible cancer cells.”

“You can think of cancer as this selfish phenomenon that dies with the individual,” Neiman adds. “But what if it didn’t? How would that change the evolutionary landscape?”

In the paper, Thomas and colleagues lay out some of the changes to the evolutionary landscape they would expect to see if their hypothesis is correct. Transmissible cancers, for example, would likely be rare in sexually reproducing species, and this is in fact the case. Only a handful of examples exist, such as Tasmanian devil facial lesions and leukemia in some clams.

The team also predicts that most asexually reproducing species would either be relatively young or els specially adapted to resist cancer. And, indeed, they found that around half of known asexual lineages are estimated to be less than 500,000 years old. “The remaining 50 percent of lineages consist of evolutionarily scandalous” organisms known to be resistant to mutagens, the new paper says. Such organisms, Thomas says, could be worth studying to learn more about their anticancer protections for medical use.

But there is a reason the origin of sex is considered a tough problem in evolutionary biology. In Neiman’s estimation, there are elements of the new theory that don’t quite add up—at least not yet. The rarity of transmissible cancers among creatures today, for example, may not support this new theory.

A “universe in which cancer was explaining sex would require that those contagious cancers were really quite common,” Neiman says. She also wonders about one of the central assumptions of the theory, that the genetic distinctness of parents and offspring would actually be a factor in successfully fighting off cancerous infection. “I am not sure it’s been well tested, and it’s a very key assumption.”

Thomas admits his team’s hypothesis needs to be validated through experimentation, which at this point is lacking. “We propose in the paper several directions for that, the most elegant one would be to use animal cloning to evaluate the risk of cancer cell transmission associated with asexual reproduction,” he says. If the new theory of sexual reproduction is correct, the likelihood that a mother passes cancer cells to her offspring should be higher if the embryo is an implanted clone of the mother, rather than a genetically distinct embryo.

The team is also working with cloned hydra, marine organisms that can reproduce both sexually and asexually depending on environmental conditions. According to Thomas Madsen, a life scientist at Deakin University and coauthor of the new study, the goal is to “try to ‘infect’ healthy clonal hydras with cancer cells and investigate their evolutionary response.” If the new theory of sex is correct, infected hydras should choose sexual reproduction over asexual.

But the origin of sex has always been messy, and Neiman believes it will stay that way. “I think the complexity and just messiness of biology is often going to demand what we call pluralistic or multiple explanations,” she says. “I don’t think there is going to be a general, elegant, single, simple solution, ever.”

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