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Genetic Secrets of the World's Most Common Sexually Transmitted Infection Revealed

It has a genome to match its global prevalence, at least as big as that of its human host
T. vaginalis



COURTESY OF ANTONIO PEREIRA-NEVES AND MARLENE BENCHIMOL, SANTA URSULA UNIVERSITY, RIO DE JANEIRO, BRAZIL
A microbe, descended from microorganisms common in the human gut, migrates to the genital region and flourishes, expanding both its size and the complexity of its genome. Trichomonas vaginalis has 10 times the genetic material of its closest microbial peers and more confirmed genes--26,000--than its human host. Plus, with the potential for up to 34,000 yet-to-be confirmed genes, the eukaryote has the biggest genome of any single-celled organism yet sequenced, according to a study in the January 12 Science. It also happens to be the infectious agent behind the estimated 170 million cases of trichomoniasis that occur worldwide every year.

That number is an approximation from the World Health Organization; despite its prevalence, most public health agencies do not track the infection, including the Centers for Disease Control and Prevention in the U.S., where the disease plagues at least eight million people. Yet, T. vaginalis infection increases susceptibility to HIV as well as causes some women to have a frothy, odoriferous discharge. "You can tell it's growing well if you have a foul smell wafting out of the dish," notes Jane Carlton, a genomist at New York University and lead author of the report.

But T. vaginalis is not interesting just for its role as a public health nemesis. Its genome is also the most repetitive ever sequenced, by far. More than 65 percent of the genetic information is a repeat, and those copies are very close. "They only diverge about 3 percent," Carlton says. "We don't currently have the computer algorithms for dealing with such a genome. It's still in thousands of pieces." In fact, it has proved extremely difficult to try to stitch the genome back together from its constituent parts.

Nevertheless, Carlton and her team were able to piece together at least 26,000 genes. Most are involved in helping the parasite cause illness as well as consume other cells, ranging from surrounding benign bacteria to the body's own red and white blood cells. But not all the genes have a clear purpose. "It has more than 800 genes coding for surface proteins and that's a huge number to have," Carlton says. "We don't know why."

One possible cause of this proliferation of genetic material is that the microbe has simply added that of some of its neighbors along the way; at least one gene appears to have crossed over from another bacteria at some point in the past, allowing the pathogen to make its own amino acid for the first time. The researchers speculate that the genome swelled in size as T. vaginalis made the bold move from its ancestral home in the gut to its new domain in the genitals, a migration that is also entirely mysterious.

Once in the vagina or the urethra, the extremely mobile T. vaginalis flattens its otherwise pear-shaped body against the wall and secretes proteins that destroy surrounding cells while consuming surrounding good bacteria to alter the overall acidity of the environment more to its liking. This multiplicity of bad habits--and swelling surface area as it flattens itself--may account for the size of the microbe's genome.

Further insights into the mystery of its outsized genome will have to wait for attempts to sequence close relatives, such as one that infests cattle and may have undergone a similar migration. "I'd like to sequence that and see if it's a similar size, which would be one way to prove our hypothesis," Carlton muses. Regardless, T. vaginalis is beginning to get the attention such a common scourge deserves. "It's the most common nonviral sexually transmitted infection, bigger than chlamydia, syphilis or gonorrhea," she adds. "Yet, it's just ignored because some people are symptomless, especially males."

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