New genomic techniques shed light on how cheetahs get their spots

Solving natural mysteries may often reveal new principles and mechanisms relevant to biology and human health. Work recently published by Greg Barsh, MD, PhD, a faculty investigator at the HudsonAlpha Institute for Biotechnology and colleagues from around the world describe how cutting-edge technology originally developed for human genome sequencing can be adapted to better understand the basis of natural color patterns.

Cells from all organisms, including non-model organisms such as the cheetah, produce messages from the genome in the form of specific molecules called RNAs. Lewis Hong, a Stanford graduate student in Barsh’s group, developed a new method called EDGE that measures the level of more than 10,000 different messages. The new method, according to Barsh, can also be applied to any cell type or tissue from any plant or animal.

Hong and Barsh first tested the method in a model organism, laboratory mice, by comparing message levels between black-haired mice and red-haired mice. The gene responsible for this hair color difference is the Melanocortin 1 receptor which also causes red hair color in humans and many other animals.

When the researchers applied the EDGE technique to cells from these mice they identified some differences already known to be controlled by the Mc1r. They also saw unexpected changes, Barsh noted, in the immune system of the mice due to the enhanced sensitivity of the technique over previous methods.

“The approach can be applied to a diverse set of questions and has the potential to help us understand other biological mysteries like how meerkats defend against snake venom or how hibernating animals survive extremes of temperature and oxygen availability,” said Barsh.

Through scientists at the Cheetah Conservation Fund in Namibia, Hong and Barsh were able to test yellow and black skin from cheetahs, as well. Results suggested that localized differences in hair color make use of Mc1r-regulated machinery, but via a different mechanism that has not yet been seen in other mammals.

In addition to Stanford and the Cheetah Conservation Fund, the work involved collaborations with scientists at Washington University in St. Louis and the National Cancer Institute, and was published in the journal Genome Research.