From Garfield Even Nurang, a feline who recently went viral by stealing the hearts of thousands of tourists at Bangkok International Airport (Thailand), orange cats have left a mark on popular culture. His image, which had already been immortalized in Renaissance paintings, is associated with a reputation for naughty, sociable, playful and chaos lovers. Beyond their unique behavior, these redhead vibrant have aroused the curiosity of science: after the origin of its color there is a genetic mystery that now has an explanation. Two independent studies conducted by American and Japanese scientists have analyzed the genetic origin of these cats.
Working each by their side, both teams reached the same conclusion, which is published this Thursday in the magazine Current Biology: The fur of orange cats is the result of genetic variations in the X chromosome, one of the two sex chromosomes. The singular thing is that this trait is linked to sex, which does not happen in any other mammal.
Gregory Barsh, from Stanford University (United States) and Hiroyuki Sasaki, from the University of Kyushu (Japan) studied with their colleagues feline genomes to determine what protein, encoded by the genes of a cat, it was the one that enhanced the orange tone. Although this genetic exception was discovered 100 years ago, the molecular identity of the mutation was unknown. Mutations usually turn off a gene or reduce its expression. In this case it is the other way around, so it is an anomaly in the DNA.
Arhgap36 is a gene of the X chromosome that encodes the protein behind the Orange effect In cats. “The color is due to the loss of a DNA fragment, which causes Arhgap36 to express abnormally in pigment cells or melanocytes. The gene is not eliminated, but is located near the site of the deletion,” Barsh explained, which can alter the reading of the DNA sequence. It is a non -dangerous mutation, in one place – as it is the fur – where it is not expected to have a negative effect.
In mammals like orangutans, dog dogs Golden retriever, tigers or humans, is this red -haired hue, but only in domestic cats the color is linked to sex, appearing more frequently in males. “We believe that this type of regulatory mutations are the main drivers of the differences between species and constitute one of the great forces of evolution,” complements the geneticist Christopher Kaelin, co -author of one of the two studies with Barsh.
The predominance of males among the orange tigrade cats had already been suspected for a long time since the redhead gene was on the X chromosome, but so far no one had identified it. After a century, that hypothesis is proven. The males, with only one sex chromosome X – the other is y – will have orange furs as long as a copy of the ARHGAP36 gene is inherited from one of their parents. The females – who have two X chromosomes – need to inherit the two copies of the gene to have a tied and completely orange fur. That is why they are much less common.
The cats that inherit a single copy of the orange gene – and the other, instead, black – show a partial color in their fur; or with a mottled pattern, known as care, or with orange, black and white spots, the typical fur called Calicó. This is produced by a genetic phenomenon called random inactivation of the X chromosome, in which one of the two copies is deactivated in each cell. As a result, a mosaic of pigment cells is formed: some express the orange and others not.
Sasaki’s team analyzed 18 cats DNA —10 redheads and eight No – and discovered that all orange cats shared a specific deletion in the gene. While US scientists performed a functional analysis using orange cells and tissues. “One of the key experiments in our study used fetal tissue of cats obtained in sterilization clinics, which helped us track how the mutation works at the cellular level,” explains Kaelin.
This happens because the cat is not an experimental model – like laboratory mice – says Priscila Ramos, head scientist of the National Institute for Agricultural and Food Technology. “The studies are based on samples obtained in clinics or animals that have died from natural causes and makes it more difficult to carry out research that involves the direct manipulation of their DNA,” adds the genetics expert.
A genetic puzzle
The ARHGAP36 gene was being investigated by scientists in the fields of cancer and development biology. It is usually expressed in neuroendocrine fabrics, where it can cause tumors. Its effect on pigment cells was not known. “In humans, (the gene) had been associated with development or cancer problems. In cats it has not been seen that it is expressed in these fabrics and when this mutation occurs only influences the production of melanin: that is why the orange hair appears,” says Ramos.
The efforts to understand how domestic cats acquired different colors and patterns, according to scientists, are an entrance door to understand the emergence of other physical features, from the stains of the Guepardo to the physiognomy of the dolphins.
The finding was facilitated, in part, by the development of cats for cats, available for a short time. Christopher Kaelin points out that much of the genetic research of the last 30 years has consisted of identifying mutations of a gene. “In our case, mutations are present in 98% of the genome,” he concludes.
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