Genetic enigma solved: Inheritance of coat color patterns in dogs

Date:
August 12, 2021
Source:
University of Bern
Summary:
Scientists have unraveled the enigma of inheritance of coat color
patterns in dogs. The researchers discovered that a genetic variant
responsible for a very light coat in dogs and wolves originated
more than two million years ago in a now extinct relative of the
modern wolf.



FULL STORY ========================================================================== [Wolf (stock | Credit: (c) Matthieu / stock.adobe.com] Wolf (stock image).

Credit: (c) Matthieu / stock.adobe.com [Wolf (stock | Credit: (c)
Matthieu / stock.adobe.com] Wolf (stock image).

Credit: (c) Matthieu / stock.adobe.com Close An international team of researchers including scientists from the Institute of Genetics of the University of Bern has unraveled the enigma of inheritance of coat color patterns in dogs. The researchers discovered that a genetic variant
responsible for a very light coat in dogs and wolves originated more
than two million years ago in a now extinct relative of the modern wolf.


==========================================================================
The inheritance of several coat color patterns in dogs has been
controversially debated for decades. Researchers including Tosso Leeb
from the Institute of Genetics of the University of Bern have now finally
been able to solve the puzzle. Not only did they clarify how the coat
color patterns are genetically controlled, but the researchers also
discovered that the light coat color in white arctic wolves and many
modern dogs is due to a genetic variant originating in a species that
went extinct a long time ago. The study has just been published in the scientific journal Nature Ecology and Evolution.

Two pigments and a "switch" for all coat colors Wolves and dogs can
make two different types of pigment, the black one, called eumelanin and
the yellow, pheomelanin. A precisely regulated production of these two
pigments at the right time and at the right place on the body gives rise
to very different coat color patterns. Prior to the study, four different patterns had been recognized in dogs and several genetic variants had
been theorized which cause these patterns. However, commercial genetic
testing of these variants in many thousands of dogs yielded conflicting results, indicating that the existing knowledge on the inheritance of
coat color patterns was incomplete and not entirely correct.

During the formation of coat color, the so-called agouti signaling
protein represents the body's main switch for the production of yellow pheomelanin. If the agouti signaling protein is present, the pigment
producing cells will synthesize yellow pheomelanin. If no agouti signaling protein is present, black eumelanin will be formed. "We realized early
on that the causative genetic variants have to be regulatory variants
which modulate the rate of protein production and lead to higher or
lower amounts of agouti signal protein," Tosso Leeb explains.

Five instead of four distinct coat color patterns The gene for agouti
signaling protein has several initiation sites for reading the genetic information, which are called promoters. Dogs, on the one hand,
have a ventral promoter, which is responsible for the production of
agouti signaling protein at the belly. On the other hand, dogs have an additional hair cycle-specific promoter that mediates the production
of agouti signaling protein during specific stages of hair growth and
enables the formation of banded hair.



==========================================================================
For the first time, the researchers characterized these two promoters in detail, in hundreds of dogs. They discovered two variants of the ventral promoter. One of the variants conveys the production of normal amounts
of agouti signaling protein. The other variant has higher activity
and causes the production of an increased amount of agouti signaling
protein. The researchers even identified three different variants of
the hair cycle-specific promoter.

Starting with these variants at the individual promoters, the researchers identified a total of five different combinations, which cause different
coat color patterns in dogs. "The textbooks have to be rewritten as there
are five instead of the previously accepted four different patterns in
dogs," Leeb says.

Unexpected insights on the evolution of wolves As many genomes from
wolves of different regions on earth have become publicly available,
the researchers further investigated whether the identified genetic
variants also exist in wolves. These analyses demonstrated that the
variants for overactive ventral and hair cycle-specific promoters were
already present in wolves prior to the domestication of modern dogs,
which started approximately 40,000 years ago. Most likely, these genetic variants facilitated adaptation of wolves with a lighter coat color to snow-rich environments during past ice ages. Today, the completely white
arctic wolves and the light colored wolves in the Himalaya still carry
these genetic variants.

Further comparisons of the gene sequences with other species of the
canidae family yielded very surprising results. The researchers were
able to show that the overactive variant of the hair cycle-specific
promoter in light-colored dogs and wolves shared more similarities with
very distantly related species such as the golden jackal or the coyote
than with the European grey wolf.

"The only plausible explanation for this unexpected finding is an
ancient origin of this variant, more than two million years ago, in
a now extinct relative of wolves," Leeb says. The gene segment must
have been introgressed more than two million years ago into wolves by hybridization events with this now extinct relative of wolves. Thus,
a small piece of DNA from this extinct species is still found today
in yellow dogs and white arctic wolves. "This is reminiscent of the
spectacular finding that modern humans carry a small proportion of DNA
in their genomes from the now extinct Neandertals," Leeb adds.

The study was enabled by a sabbatical done by Prof. Danika Bannasch at the University of Bern with its longstanding research focus on the genetics
of coat color in domestic animals. Bannasch, a professor in veterinary
genetics at the University of California Davis, filtered the relevant
promoter variants from thousands of other functionally neutral genetic variants. The evolutionary analyses were conducted by Christopher Kaelin
and Gregory Barsh of the HudsonAlpha Institute and Stanford University.

The study was financially supported by grants from the Swiss National
Science Foundation SNSF, Maxine Adler Endowed Chair Funds, Jane and
Aatos Erkko Foundation, and the Academy of Finland.

========================================================================== Story Source: Materials provided by University_of_Bern. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Danika L. Bannasch, Christopher B. Kaelin, Anna Letko, Robert
Loechel,
Petra Hug, Vidhya Jagannathan, Jan Henkel, Petra Roosje, Marjo K.

Hyto"nen, Hannes Lohi, Meharji Arumilli, Hannes Lohi, Juha Kere,
Carsten Daub, Marjo Hyto"nen, Ce'sar L. Araujo, Ileana B. Quintero,
Kaisa Kyo"stila", Maria Kaukonen, Meharji Arumilli, Milla Salonen,
Riika Sarviaho, Julia Niskanen, Sruthi Hundi, Jenni Puurunen,
Sini Sulkama, Sini Karjalainen, Antti Sukura, Pernilla Syrja",
Niina Airas, Henna Pekkarinen, Ilona Kareinen, Anna Knuuttila, Heli
Nordgren, Karoliina Hagner, Tarja Pa"a"kko"nen, Antti Iivanainen,
Kaarel Krjutskov, Sini Ezer, Auli Saarinen, Shintaro Katayama,
Masahito Yoshihara, Matthias Ho"rtenhuber, Rasha Fahad Aljelaify,
Fiona Ross, Amitha Raman, Irene Stevens, Oleg Gusev, Danika
L. Bannasch, Jeffrey J. Schoenebeck, Katie M.

Minor, James R. Mickelson, Cord Dro"gemu"ller, Gregory S. Barsh,
Tosso Leeb. Dog colour patterns explained by modular promoters
of ancient canid origin. Nature Ecology & Evolution, 2021; DOI:
10.1038/s41559-021-01524-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210812145103.htm

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