Tiger, Tiger, Burning Bright, Just One Gene To Make It White

White tigers were first recorded in India in the 1500s, but the last wild one was shot in 1958. Still, this spectral animal thrives in captivity. Its captivating white coat and blue eyes have made it a popular mainstay of zoos, and a small number of individuals have been repeatedly bred with each other to boost captive numbers. There were just a few dozen in the 1970s. Now, there are hundreds.

The white tiger isn’t a species in its own right, or even a subspecies. Instead, it’s a mutant version of the Bengal tiger, whose orange coat has whitened thanks to an extremely rare recessive gene. If a tiger inherits two copies of this recessive variant, one from each parent, it’s white. If it has even one normal copy, it’s orange.

Back in the 1970s, Roy Robinson suggested that the gene in question was tyrosinase (TYR). It’s involved in making melanin—a pigment responsible for black, brown, red and yellow colours. If individuals have faulty versions of TYR, they are born without melanin and have pale hair, skin and eyes—they’re called albinos.

The white tiger isn’t a true albino since it still has black pigment in its stripes and eyes. Instead, Robinson thought that it carries chinchilla—a version of the TYR gene that only removes the type of melanin behind yellow and red colours. Without this, the orange coat becomes white, but the black bits stay black. Mystery solved.

You’ll still find this explanation all over the internet, but Xiao Xu from Peking University showed that Robinson was wrong. White tigers have the same version of TYR as orange ones. They also carry identical variants of four other genes that affect the colour of mammal coats. These include MC1R, the gene responsible the white coats of “snow coyotes” and “spirit bears”.

To find the real culprit behind the white coats, Xu’s team compared the DNA of 7 white tigers and 9 orange ones, living in China’s Chimelong Safari Park. They’re all related, and you can see their family tree below. The team sequenced the entire genomes of the three parents, identified more than 170,000 places where their DNA varied between individuals, and sequenced these locations in the rest of the animals.

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Family tree of tigers involved in this study. Credit: Xu et al, 2013. Current Biology, Cell Press

Gradually, they homed in on seven genes that consistently differed in the white and orange animals. And by looking at these genes in 130 more tigers, from several unrelated sources, the team narrowed their list down to just one.

It has the tremendously catchy name of SLC45A2. It’s also involved in making melanin, although no one is entirely sure how. Variations in the gene have been linked to lighter skin or hair in mice, horses, chickens, medaka fish and humans. It’s associated with light skin colour in modern Europeans, as well as one type of albinism.

The SLC45A2 gene makes a protein of the same name, which consists of 560 amino acids. A single mutation in the gene—a change in just one DNA letter—switches one of those 560 amino acids from an alanine to a valine. This distorts the protein’s shape, and potentially prevents it from taking part in the creation of red-yellow melanin. Every white tiger has two copies of this mutated gene, and can only make the distorted protein. That’s all it takes to change their coats from orange to white.

Greg Barsh from the HudsonAlpha Institute of Biotechnology thinks that Xu’s team have found the right gene, and their results might eventually help to explain exactly what SLC45A2 does. In other species, mutations in the gene usually interfere with both the red-yellow and brown-black types of melanin. But in the tigers, they just disrupt the red-yellow pigments. Mutations in the TYR gene can sometimes do the same—remember chinchilla?—so even though Robinson was wrong about the gene behind the white coats, it’s still possible that SLC45A2 somehow interacts with TYR.

Some people have suggested that the genes behind the white coat also cause other defects, which have become more prominent because the captive animals are so inbred. These include club feet, crossed eyes, cleft palates, and hip or spine problems.

But Xu’s team argue that the white coat is the result of a pigmentation problem, and nothing more. After all, white tigers did once exist in the wild, and those that were captured or shot were often mature adults. This suggests that they’re capable of surviving in the wild despite their mutation—possibly because they hunt colour-blind prey.

Barsh disagrees. “Many humans and other animals with SLC45A2 mutations have severe visual problems,” he says, and he notes that previous studies have found abnormal visual connections between the tigers’ eyes and brains. This might explain the crossed eyes of the captive animals, and probably means that the mutation did affect the white tigers’ survival in the wild.

All of this feeds into a longstanding debate about the role that these white beasts should play in tiger conservation. Writing in Slate, Jackson Landers argues that white tigers should play no role in breeding programmes or reintroduction efforts, and should be allowed to “disappear into memory”. Every zoo enclosure that houses one is an enclosure that isn’t preserving one of the genuinely endangered tiger subspecies, whose numbers and genetic diversity are dwindling.

Xu’s team argues, based on their results, that the white tiger “should be considered a part of the genetic diversity of tigers that is worth conserving”. They argue that both white and orange tigers should be used to boost the Bengal population, and that reintroductions are possible.

It’s hard to see how their results address that issue, though. Given the past existence of wild white tigers, it’s clear that the white mutation was indeed a naturally occurring one—we just know which gene it affects now. Identifying SLC45A2 doesn’t change the fact that white tigers do suffer from several abnormalities, thanks to generations of inbreeding.

And with fewer than 3,200 tigers left in the wild, it’s perhaps a distraction to worry about conserving this one mutant gene. As John Seidensticker form the Smithsonian National Zoological Park bluntly puts it, “We have much more pressing tiger conservation problems.”

Reference: Xu, Dong, Hu, Miao, Zhang, Zhang, Yang, Zhang, Zou, Zhang, Zhuang, Bhak, Cho, Dai, Jiang, Xie, Li & Luo. 2013. The Genetic Basis of White Tigers. Current Biology. http://dx.doi.org/10.1016/j.cub.2013.04.054

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