A new study led by Dr Vincent Lynch from the University of Chicago has identified extensive genetic changes responsible for what makes a woolly mammoth a woolly mammoth, including genes linked to skin and hair development, fat metabolism, insulin signaling, and even physical traits such as skull shape, small ears and short tails. As a test of function, Dr Lynch and co-authors resurrected a woolly mammoth gene involved in temperature sensation.

To identify the genetic changes that underlie the suite of woolly mammoth adaptations to extreme cold, Dr Lynch’s team sequenced the nuclear genome from three Asian elephants and two woolly mammoths (Mammuthus primigenius)

The scientists identified roughly 1.4 million genetic variants unique to woolly mammoths. These caused changes to the proteins produced by around 1,600 genes, including 26 that lost function and one that was duplicated.

To infer the functional effects of these differences, the team ran multiple computational analyses, including comparisons to massive databases of known gene functions and of mice in which genes are artificially deactivated.

“This is by far the most comprehensive study to look at the genetic changes that make a woolly mammoth a woolly mammoth. They are an excellent model to understand how morphological evolution works, because mammoths are so closely related to living elephants, which have none of the traits they had,” said Dr Lynch, first author of the paper reporting the results in the journal Cell Reports (bioRxiv.org preprint).

Of particular interest was the group of genes responsible for temperature sensation, which also play roles in hair growth and fat storage.

The researchers used ancestral sequence reconstruction techniques to revive the mammoth version of one of these genes, TRPV3.

When transplanted into human cells in the lab, TRPV3 produced a protein that is less responsive to heat than an ancestral elephant version of the gene.

This result is supported by observations in mice that have TRPV3 artificially silenced. These mice prefer colder environments than normal mice and have wavier hair.

Although the functions of these genes match well with the environment in which woolly mammoths were known to live, the scientists warn that it is not direct proof of their effects in live mammoths.

“We can’t know with absolute certainty the effects of these genes unless someone resurrects a complete woolly mammoth, but we can try to infer by doing experiments in the laboratory,” Dr Lynch concluded.

_____

Vincent J. Lynch et al. Elephantid Genomes Reveal the Molecular Bases of Woolly Mammoth Adaptations to the Arctic. Cell Reports, published online July 02, 2015; doi: 10.1016/j.celrep.2015.06.027