Darwin's short-beak enigma solved
Mutation in the ROR2 gene is linked to beak length in domestic pigeons,
has a surprising connection with a human congenital disorder

Date:
September 21, 2021
Source:
University of Utah
Summary:
Biologists discovered that a mutation in the ROR2 gene is
linked to beak size reduction in numerous breeds of domestic
pigeons. Surprisingly, different mutations in ROR2 also underlie
a human disorder called Robinow syndrome. The ROR2 signaling
pathway plays an important role in the craniofacial development
of all vertebrates.



FULL STORY ========================================================================== Charles Darwin was obsessed with domestic pigeons. He thought they held
the secrets of selection in their beaks. Free from the bonds of natural selection, the 350-plus breeds of domestic pigeons have beaks of all
shapes and sizes within a single species (Columba livia). The most
striking are beaks so short that they sometimes prevent parents from
feeding their own young. Centuries of interbreeding taught early pigeon fanciers that beak length was likely regulated by just a few heritable
factors. Yet modern geneticists have failed to solve Darwin's mystery by pinpointing the molecular machinery controlling short beaks -- until now.


==========================================================================
In a new study, biologists from the University of Utah discovered that
a mutation in the ROR2 gene is linked to beak size reduction in numerous
breeds of domestic pigeons. Surprisingly, mutations in ROR2 also underlie
a human disorder called Robinow syndrome.

"Some of the most striking characteristics of Robinow syndrome are the
facial features, which include a broad, prominent forehead and a short,
wide nose and mouth, and are reminiscent of the short-beak phenotype
in pigeons," said Elena Boer, lead author of the paper who completed
the research as a postdoctoral fellow at the U and is now a clinical
variant scientist at ARUP Laboratories.

"It makes sense from a developmental standpoint, because we know that the
ROR2 signaling pathway plays an important role in vertebrate craniofacial development." The paper published in the journal Current Biology on
Sept. 21, 2021.

Mapping genes and skulls The researchers bred two pigeons with short and
medium beaks -- the medium- beaked male was a Racing Homer, a bird bred
for speed with a beak length similar to the ancestral rock pigeon. The small-beaked female was an Old German Owl, a fancy pigeon breed that
has a little, squat beak.



========================================================================== "Breeders selected this beak purely for aesthetics to the point that it's detrimental -- it would never appear in nature. So, domestic pigeons are
a huge advantage for finding genes responsible for size differences,"
said Michael Shapiro, the James E. Talmage Presidential Endowed Chair
in Biology at the U and senior author of the paper. "One of Darwin's
big arguments was that natural selection and artificial selection are variations of the same process. Pigeon beak sizes were instrumental in
figuring out how that works." The short- and medium-beaked parents
produced an initial F1 brood of children with intermediate-length
beaks. When the biologists mated the F1 birds to one another, the
resulting F2 grandchildren had beaks ranging from big to little, and all
sizes in between. To quantify the variation, Boer measured beak size
and shape in the 145 F2 individuals using micro-CT scans generated at
the University of Utah Preclinical Imaging Core Facility.

"The cool thing about this method is that it allows us to look at size
and shape of the entire skull, and it turns out that it's not just beak
length that differs -- the braincase changes shape at the same time,"
Boer said. "These analyses demonstrated that beak variation within the F2 population was due to actual differences in beak length and not variation
in overall skull or body size." Next, the researchers compared the
pigeons' genomes. First, using a technique called quantitative trait loci
(QTL) mapping, they identified DNA sequence variants scattered throughout
the genome, and then looked to see if those mutations appeared in the
F2 grandkids' chromosomes.

"The grandkids with small beaks had the same piece of chromosome as their grandparent with the small beak, which told us that piece of chromosome
has something to do with small beaks," said Shapiro. "And it was on the
sex chromosome, which classical genetic experiments had suggested, so
we got excited." The team then compared the entire genome sequences of
many different pigeon breeds; 56 pigeons from 31 short-beaked breeds and
121 pigeons from 58 medium- or long-beaked breeds. The analysis showed
that all individuals with small beaks had the same DNA sequence in an
area of the genome that contains the ROR2 gene.



==========================================================================
"The fact that we got the same strong signal from two independent
approaches was really exciting and provided an additional level of
evidence that the ROR2 locus is involved," said Boer.

The authors speculate that the short-beak mutation causes the ROR2 protein
to fold in a new way, but the team plans to do functional experiments
to figure out how the mutation impacts craniofacial development.

Pigeon enthusiasts The lure of the domestic pigeon that mesmerized
Darwin is still captivating the curious to this day. Many of the blood
samples that the research team used for genome sequencing were donated
from members of the Utah Pigeon Club and National Pigeon Association,
groups of pigeon enthusiasts who continue to breed pigeons and participate
in competitions to show off the striking variation among breeds.

"Every paper our lab has published in the last 10 years
has relied on their samples in some way," said Shapiro. "We
couldn't have done this without the pigeon breeding community." ========================================================================== Story Source: Materials provided by University_of_Utah. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Elena F. Boer, Hannah F. Van Hollebeke, Emily T. Maclary, Carson
Holt,
Mark Yandell, Michael D. Shapiro. A ROR2 coding variant is
associated with craniofacial variation in domestic pigeons. Current
Biology, 2021; DOI: 10.1016/j.cub.2021.08.068 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210921125156.htm

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