Cancer evidence found in the gene behind “Lemon Frost” Gecko Color

When reptile breeder Steve Sykes saw that two specific leopard geckos were being auctioned in 2015, he knew he had to have them. The bodies of the chubby lizards were covered with black spots, which gave their species their common name. And at eye level, they looked like they were smiling. But unlike other members of Eublepharis maculariusThey were “lemon frost” geckos: They were pastel yellow from the base of the head to the base of the tail, as if they had been dipped in lemon sorbet. A breeder had only created this strain, also known as “Morph”, a generation earlier. The combination of rarity and beauty made the two geckos immediately attractive to Sykes. He bought the pair and named them Mr. and Ms. Frosty.

Leopard geckos are among the most common reptile pets. Native to the Middle East and South Asia, they have been bred so successfully in captivity that most of the animals sold today are not from the wild. Instead, the owners create and mix dozens of morphs through selective breeding and random luck.

“It’s a big deal when a brand new base morph comes out, no matter what it is. The fact that there was a lemon frost was definitely something I wanted to add to my collection, ”says Sykes, who owns a company called Geckos Etc. Herpetoculture. “Little did I know there was a problem with this morph when I first looked at it.”

The problem arose with Mr. Frosty’s offspring. Sykes had bred the male with other leopard geckos he owned to produce more of the coveted lemon frost. A year after the auction, he noticed small, white bumps on the bodies of some babies. Over time it became clear that these bumps were tumors. In fact, it turns out that more than 80 percent of geckos with this morph have a rare skin cancer that develops from pigment-producing cells called iridophores.

Sykes wanted to know if there was any way to grow lemon frost to avoid that fate. Were the cancer and the unique color inextricably linked? Evolutionary geneticist Leonid Kruglyak of the University of California, Los Angeles, and his colleagues used Sykes’ geckos to crack the lemon frost genetic code – and found that a single gene controlled both color and cancer.

“Very little molecular genetic work has been done on reptiles, so it’s fantastic to see a case where a group has been able to trace the genetic basis of a really interesting trait,” says Douglas Menke, a geneticist at the University of Georgia was consulted for the study but was not directly involved in the work.

This research could also open new avenues for research into human melanoma, an aggressive cancer of our pigment-producing cells. It is newly diagnosed in about 100,000 people in the United States each year and kills more than 7,000 annually.

Gecko detective work

In 2017, shortly after discovering the lemon frost morph’s propensity for tumors, Sykes said he received a call from Longhua Guo, a postdoctoral fellow in Kruglyak’s laboratory researching human genetics. Guo had seen photos of leopard geckos on the Internet and was intrigued by how their genes control their vibrant and diverse patterns. After a two-hour conversation, says Guo, Sykes convinced him to investigate the secret of the lemon frost tumor.

Since Sykes had already bred the geckos with the intent of selling them before he noticed the cancer, the researchers had access to dozens of Mr. Frosty’s children and grandchildren. They collected DNA samples by cutting a small piece of a gecko’s tail or dabbing the inside of the cheek – relatively easy tasks, Guo says, because of the lizards’ relaxed temperament. The team then compared the sequenced genomes of the lemon frost gecko with an existing genome of a standard leopard gecko.

The results couldn’t have been clearer: Lemon frost geckos had a copy of a gene named SPINT1 that was mutated. Your other copy of this gene, as well as both copies in non-lemon frost leopard geckos, did not have these differences in DNA sequence.

“It turns out that SPINT1 can explain what’s going on here because SPINT1 has been reported in zebrafish, mice and humans. [Mutations in the gene] have been associated with skin cell tumors, ”says Guo. Looking at the tumors of the lemon frost under a high-powered microscope revealed an increased number of iridophores, which give some lizard scales a whitish appearance.

Guo and his team suggested that the mutated copy of SPINT1 causes lemon frost geckos to overproduce these cells. This overproduction would result in an overall whiter background, which makes the animals’ yellow color appear brighter and more visible – and that could can also lead to skin tumors later in life. The study, authored by Guo, Sykes, Kruglyak, and their colleagues, was released on Thursday in. released PLOS genetics.

A frosty model organism

Researchers still don’t know why some lemon frosts have more aggressive cancers than their siblings, or why others (including Mr. Frosty himself) never develop visible tumors. “Why does Gecko A develop no tumors at all, while Gecko B has very light tumors that remain completely dormant for a very long time and Gecko C has very fast growing and very active tumors?” Asks Sykes. “That was always a question for me.”

Answering this question could help scientists better understand how some cancers develop in humans, says Lara Urban, a conservation genomics research fellow at the University of Otago in New Zealand who was not involved in the study. “I think it will have an impact on cancer research because we know how conserved this is [SPINT1 genetic] Away a little better now, ”she says. “It will also be a potential new model organism to study the development of skin cancer and contribute to actual therapeutic development.”

Perhaps there are tumor suppressor genes that keep cancer in check in some lizards and not in others, Urban adds. And if the tumors are inevitable, they could have certain chemical signatures that current methods cannot detect. This opens up the possibility of finally developing diagnostics for the detection of preclinical melanomas in humans.

While the lemon frost morph could be bred as a research strain, Sykes says the lizards are unlikely to be sold as hobby pets ever again.

“We stopped growing lemon frosts and we have no intention of starting them again in the future,” he says. “My goal is to produce beautiful, perfect and healthy geckos. And it doesn’t seem to be possible to separate the lemon frost gene from this tumor phenotype. “