Rodent ancestors combined portions of blood and venom genes to make
pheromones
Over 100 genomes searched to find origin of pheromone gene family

Date:
September 30, 2020
Source:
University of Tokyo
Summary:
Experts who study animal pheromones have traced the evolutionary
origins of genes that allow mice, rats and other rodents to
communicate through smell. The discovery is a clear example of
how new genes can evolve through the random chance of molecular
tinkering and may make identifying new pheromones easier in future
studies. The results represent a genealogy for the exocrine-gland
secreting peptide (ESP) gene family.



FULL STORY ========================================================================== Experts who study animal pheromones have traced the evolutionary origins
of genes that allow mice, rats and other rodents to communicate through
smell. The discovery is a clear example of how new genes can evolve
through the random chance of molecular tinkering and may make identifying
new pheromones easier in future studies. The results, representing a
genealogy for the exocrine-gland secreting peptide (ESP) gene family,
were published by researchers at the University of Tokyo in the journal Molecular Biology and Evolution.


========================================================================== Researchers led by Professor Kazushige Touhara in the University of Tokyo Laboratory of Biological Chemistry previously studied ESP proteins that
affect mice's social or sexual behavior when secreted in one mouse's
tears or saliva and spread to other animals through social touch.

Recently, Project Associate Professor Yoshihito Niimura led a search for
the evolutionary origin of ESP genes using the wide variety of fully
sequenced animal genomes available in modern DNA databases. Niimura
looked for ESP genes in 100 different mammals and found them only in two evolutionarily closely related families of rodents: the Muridae family of
mice, rats and gerbils, and the Cricetidae family of hamsters and voles.

Notably, the Cricetidae had few ESP genes usually all grouped together in
the same stretch of DNA, but the Muridae had both that same small group
of ESP genes as well as a second, larger group of additional ESP genes.

"We can imagine about 35 million years ago, the common ancestor of Muridae
and Cricetidae formed the first ESP genes. Eventually, approximately
30 million years ago, the ancestor of Muridae duplicated and expanded
these ESP genes. So now mice have many more ESP genes than the Cricetidae rodents," said Niimura.

To identify the source of what formed the first ESP gene, researchers
compared additional genome sequences. They uncovered how random
chance copied uniquely functional portions of two other genes, then coincidentally pasted them next to each other.



==========================================================================
The DNA sequence of a gene includes portions called exons, which later
become the functional protein, and other portions called introns, which
do not become protein. Introns and exons are spaced throughout the gene
with no apparent organization, introns interrupting essential functional portions of exons.

Therefore, if a single exon were randomly copied and pasted elsewhere
in the genome, any resulting protein fragment would have no meaningful function.

However, if an exon-only version of a gene were copied and reinserted
into the genome, the chances of that new sequence remaining functional
become much greater. Cells do create exon-only versions of genes called
mRNA as part of the normal process of making protein from genes and
cells do possess machinery, likely left over from viral infections,
that can copy mRNA back into the DNA strand.

"This is not the normal way of things in cells, but it is a common
source of evolution. We guess this is what happened to make ESP genes
because the whole functional portion of the ESP gene is one exon, no
intron interruption," said Niimura.

Specifically, the research team discovered for the first time that ESP
proteins contain an uncommon spiral shape characteristic of alpha-globin,
a component of the iron-carrying hemoglobin protein in blood. DNA
sequence comparisons revealed that multiple alpha-globin gene exons
spliced together show a subtle but distinctive similarity to the ESP
gene sequence.

"It doesn't matter that hemoglobin is the source of the ESP pheromone. Any protein can become a pheromone if it is used for species-specific communication," said Niimura.

Regardless of its shape, no protein can function without being in the
proper location. In ESP proteins, the alpha-globin-derived portion
is attached to a signaling portion, which directs the protein to be
secreted from salivary and tear glands. Researchers identified the ESP
genes' location signaling sequence as resembling that of CRISP2, a gene expressed in mammalian reproductive tracts and salivary glands as well
as the venom gland of some snakes.

The hemoglobin and CRISP genes are both ancient genes that existed in the shared evolutionary ancestor of vertebrates -- all animals with a backbone
- - over 500 million years ago. The genetic shuffling that created ESP
genes occurs relatively frequently in the cells of all organisms, but for
these changes to become inherited evolutionary traits, the changes must
occur in the sex cells so they can be passed on to future generations.

"The creation of new genes is not done from scratch, but nature utilizes
pre- existing material. Evolution is like a tinkerer, using old things
and broken parts to create some new device with a useful function,"
said Niimura.

Niimura and his colleagues plan to use their new understanding of the
evolution of this one family of pheromones to direct their search for new pheromones. The short length of many known pheromone genes makes it likely
that similar pheromones are overlooked in standard genome searches. They
also predict that salivary and tear glands, often overlooked because
their small size makes them inconvenient tissues to study, may contain interesting future discoveries.


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


========================================================================== Journal Reference:
1. Yoshihito Niimura, Mai Tsunoda, Sari Kato, Ken Murata, Taichi
Yanagawa,
Shunta Suzuki, Kazushige Touhara. Origin and evolution of the gene
family of proteinaceous pheromones, the exocrine gland-secreting
peptides, in rodents. Molecular Biology and Evolution, 2020; DOI:
10.1093/molbev/ msaa220 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200930110131.htm

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