A new analysis of genital human papillomavirus (HPV) in men shows that infection with one HPV type strongly increases the risk of reinfection with the same type. In fact, men who are infected with the type responsible for most HPV-related cancers are 20 times more likely to be reinfected within one year. This increased risk suggests that infection confers no natural immunity against HPV, as is often the case with other viruses.
The study, published December 5 in the Proceedings of the National Academy of Sciences, highlights the importance of vaccination for preventing the spread of HPV in young men before they become sexually active. Vaccination could potentially prevent reinfection in older men who have already contracted the virus.
“Vaccinating boys before HPV exposure could be a highly effective way to reduce the burden of HPV infection. Vaccinating men who have already been infected might also be effective,” said Sylvia Ranjeva, a PhD student in the University of Chicago Department of Ecology and Evolution and the Pritzker School of Medicine, who led the study.
HPV is the most common sexually transmitted infection. Approximately 40 percent of women and 45 percent of men in the United States are infected, and it is a major cause of genital warts and cancers of the genitals, mouth and throat. There are more than 200 genetically-distinct HPV types; vaccines protect against four to nine of the most common, disease-causing types.
Ranjeva and her UChicago colleagues, including Greg Dwyer, PhD, professor of ecology and evolution and Sarah Cobey, PhD, assistant professor of ecology and evolution, wanted to understand what allowed so many different types of HPV to coexist. They analyzed data regarding the spread of the disease from the HPV in Men study, which tracked more than 4,000 unvaccinated men from three cities in Florida, Mexico and Brazil over five years from 2005 to 2009.
Usually, diversity of so many types of viruses happens as they compete to evolve different ways to evade the immune defenses of hosts. The new analysis showed no evidence of such competition among HPV types, however. Instead, the diversity of HPV types may stem from recurring infections of particular types within individuals. While relatively few people are infected with any one type, the high overall HPV prevalence occurs because nearly half the adult population carries at least one type of genital HPV. The high risk of reinfection may be due to either auto-inoculation, spreading the infection by repeated contact between different sites on the body, or reactivation of a latent virus.
The results also show that men who are infected once with HPV16, the type responsible for most HPV-related cancers, are at 20 times higher risk of reinfection after one year, and 14 times higher after two years. The researchers saw the same effect in both men who are sexually active and celibate, suggesting that they are not reacquiring the virus from another sexual partner.
“That’s what makes this a biologically significant result,” Ranjeva said. “The best thing we can do is prevent the initial infection by vaccinating boys before sexual contact. However, if the increased risk of reinfection is due to auto-inoculation, then another effective strategy may be to vaccinate previously infected men as well.”
The study, “Recurring infection with ecologically distinct human papillomavirus (HPV) types explains high prevalence and diversity,” was supported by the National Institutes of Health. Additional authors include Edward Baskerville from the University of Chicago; Vanja Dukic and Anna Giuliano from the H. Lee Moffitt Cancer Center; Luisa Villa from Universidade de Sao Paulo, Brazil; and Eduardo Lazcano-Ponce from Instituto Nacional de Salud Publica, Cuernavaca, Mexico.
Bacteria surround us everywhere we go. They inhabit every corner of our world, from the places we work and live to the insides of our own bodies. They play an enormous role in our health and well-being, from the development of disease and allergies to how we respond to medicine—and they have the final say in death as well.
Jack Gilbert, faculty director of the Microbiome Center at the University of Chicago, and Gulnaz Javan, a forensic scientist from Alabama State University, received a two-year, $532,000 grant from the National Institute of Justice to study the thanatomicrobiome, or “microbiome of death.” The term was coined by Javan to describe the collection of microbes from internal organs collected during criminal casework. The project will develop tools to help determine the time and cause of death by identifying patterns of bacterial growth in a corpse’s internal organs after death.
Previous work by Gilbert in 2016 showed how bacteria can help pinpoint the time and place of death, but he and Javan also want to see how stress on the body at the time of death leaves a unique signature on microbiota in the organs. The team will work with cadavers from national morgues in Montgomery, Ala., and Pensacola, Fla., plus an international morgue in Tampere, Finland, the largest morgue in that country. They will also explore relationships with morgues in Italy to increase the size and diversity of human corpses and organs that can be studied.
“The aim of this study is to determine whether we can calculate the time of death based on the bacteria that have escaped their normal body habitats and invaded internal organs” Gilbert said. “Once the body dies, the immune system fails and your microbiome is set free – we can track how the microbes migrate by examining the organs of hundreds of bodies.”
The team also hopes to determine if the microbial signature of the organs has any predictive ability when it comes to determining how the individual died.
“We have samples from natural deaths through murders, and we expect to be able to find a signature of how the person died based on the specific bacteria that colonize the organs first,” Gilbert said.
The study will run from January 2018 through December 2019.
Tagged: Biological Sciences, crime investigation, death, decomposition, forensics, Jack Gilbert, Microbiology, microbiome
Female swallowtail butterflies do something a lot of butterflies do to survive: they mimic wing patterns, shapes and colors of other species that are toxic to predators. Some – but not all – swallowtail species have evolved several different forms of this trait. But what kind of genetic changes led to these various disguises, and why would some species maintain an undisguised form when mimicry provides an obvious evolutionary advantage?
In a new study published this week in Nature Communications, scientists from the University of Chicago analyze genetic data from a group of swallowtail species to find out when and how mimicry first evolved, and what has been driving those changes since then. It’s a story that started around two million years ago, but instead of steady, progressive changes, one chance genetic switch helped create the first swallowtail mimics. And it has stuck around ever since.
“In butterflies with one color pattern, we have a gene in a normal orientation on the chromosome. In the butterflies with the unusual, alternate color pattern, that gene was spliced out, flipped, and then spliced back into the chromosome at some point,” said Marcus Kronforst, PhD, associate professor of ecology and evolution at UChicago and the senior author of the study.
“That flip, or inversion, keeps the two genes from recombining if those two different kinds of butterflies mate, so they’ve kept both copies of the gene over evolutionary time, since they split from their common ancestor two million years ago,” Kronforst said.
For a long time, scientists thought that butterfly mimicry was controlled by “supergenes,” groups of several tightly linked genes that were always inherited as a group. In a 2014 study, Kronforst and his colleagues showed what appears to be a supergene is actually a single gene called doublesex that controls the different color patterns and shapes we see in female swallowtails.
The doublesex gene was already well-known for its role in differentiating between sexes, but in females the inverted, or flipped, version also dictates wing patterns. It can still be thought of as a supergene because it controls the entire, complex process of wing patterning, but in this case, it is just the single gene.
In the new study, led by postdoctoral fellow Wei Zhang, PhD, the team analyzed whole-genome sequence data form Papilio polytes, the Asian swallowtail butterfly, and several similar species to see how they are related to each other, and how their copies of doublesex compare. Using these data, the team compared some alternative explanations for the origins of mimicry and identified key factors that have maintained different forms of mimicry long-term.
The most closely related species to the P. polytes group, called Papilio protenor, is spread across mainland Asia from India to Japan and did not develop mimicry—both males and females look alike. Other species that spread from the mainland to islands in the Philippines and Indonesia developed three or four distinct forms, a feature known as polymorphism. Still other swallowtail species spread further to Papua New Guinea and the northeast coast of Australia, but those females display only one disguised wing pattern.
The researchers compared the patterns they saw in the genome sequence data to some possible explanations for how these patterns of mimicry developed over time and geography. Did mimicry evolve independently in different species at different points in time? Did it evolve in one species, and then spread through cross-breeding or hybridization?
It appears that mimicry actually has a single ancient origin, when the doublesex gene flipped two million years ago. Since that initial inversion, Zhang and Kronforst did see signs of what’s known as balancing selection. When one type of butterfly becomes more common, predators realize they aren’t toxic and start to feed on them. This reduces the number of that particular butterfly, until another one becomes more common, and so on. Eventually this process balances out and preserves the relative number of each form.
They also saw that some butterfly populations have maintained multiple female forms for millions of years, while others lost the original, undisguised form. Historically, the smallest groups—e.g. the ones that spread the furthest to Australia—lost the polymorphism, allowing random genetic drift and natural selection to weed out the original form.
The researchers also looked at what maintained polymorphism over time. One cause could be sexual selection, that males prefer certain female color patterns over another. Previous research on mating behavior doesn’t back up that idea though. Another possibility is “crypsis,” or the idea that undisguised females blend into their natural surroundings better than the mimics. Kronforst and the team tested that hypothesis by comparing mimetic and non-mimetic females against a green forest background using models for predator (i.e. bird) vision. The non-mimetic, undisguised females actually don’t blend in to the background any more than mimics, so this idea is out too.
Those two findings, combined with the genomic sequence data, led the researchers to start thinking about another intriguing possibility. It could be that the genetic changes that led to mimicry in the first place also built in some long-term disadvantages. When the original doublesex gene inverted, it probably carried a bunch of other unrelated genetic material with it. Since the flipped doublesex gene can’t be recombined with its original version, the extra stuff has “hitchhiked” ever since—and it could have consequences. In fact, some research shows that female mimics don’t live as long as standard ones.
“We think a bunch of differences were accidentally captured when one copy of the gene flipped and became the mimetic copy. Because a lot of those changes are functional, they could be detrimental to health,” Kronforst said.
“The idea is that you have this hardwired disadvantage to mimicry. The standard females don’t have the protection of mimicry, but they also don’t have this inherent genetic cost and these two things offset one another” he said.
Now that they have unraveled some of the history behind the evolution of mimicry, Kronforst said his team wants to start looking for the specific genetic mutations on doublesex that cause different kinds of mimicry.
“If we can find ways to piece through all the differences that we see, we should be able to narrow it down to something much more discrete than all the differences we see now,” he said.
The study, “Tracing the origin and evolution of supergene mimicry in butterflies,” was supported by University of Chicago Neubauer research funds, a Pew Biomedical Scholars Fellowship, the National Science Foundation and the National Institutes of Health. Additional authors include Erica Westerman from the University of Arkansas, along with Eyal Nitzany and Stephanie Palmer from the University of Chicago.
Tagged: Biological Sciences, butterflies, Evolution, Genetics, insects, Marcus Kronforst, mimicry