April 30, 2000
Gene Tug-of-War Leads to Distinct Species
By crossing two mouse species that normally do not interbreed,
Howard Hughes Medical Institute (HHMI) researchers have gained a better
understanding of how gene imprinting can influence the establishment of
distinct species.
The majority of mammalian genes are present in two copies that are
expressed and regulated. A small number of mammalian genes, however,
are subject to special regulation by a process called gene imprinting.
The imprint is a chemical mark attached to genes during egg or sperm
development. Imprinting physically marks a gene in such a way that the
parental origin of the gene can be distinguished and expressed
accordingly.
“We showed that the differences in phenotypes seen in hybrids that are affected by the parent of origin — for example overgrown animals versus small — really do have something to do with imprinting.”
Paul B. Vrana
Most imprinted genes seem to govern fetal growth regulation,
explained Shirley M. Tilghman, an HHMI investigator at Princeton
University. Some researchers speculate that imprinting evolved in order
to establish boundaries between species. Imprinting is also thought to
provide a barrier to unisexual reproduction and the interbreeding of
species.
An hypothesis about the origin of imprinting, favored by Tilghman
and her colleagues, is that imprinting was created as the result of a
parental "tug-of-war." According to the theory, fathers contribute
genes that enhance growth because their best interests are served if
their progeny extract as many maternal resources as possible in order
to ensure survival. Mothers, on the other hand, then silence their copy
of growth-promoting genes in retaliation because they value all of
their progeny equally.
In a research article published in the May 2000 issue of the journal
Nature Genetics, Tilghman and colleagues at Princeton report
that crossing two related mouse species, Peromyscus polionotus
and Peromyscus maniculatus, results in abnormalities in gene
imprinting and growth abnormalities in the hybrid offspring.
"We chose these particular species to explore the mechanism of
imprinting because Dr. Wally Dawson at the University of South Carolina
showed 35 years ago that the abnormal growth seen in the hybrid mice
depends on the "direction" of crosses between the two species," said
Tilghman. "This suggested to us that the hybrids may have defects in
imprinting, and our first idea was that one of the species was not
imprinting normally. However, we showed that this was not the case;
both species imprint correctly. It is when they hybridize that
imprinting goes awry."
Disruptions in growth are thought to contribute to speciation — the
process by which one species gives rise to two others — because they
may reflect a rapidly evolving divergence between species that prevents
viable interbreeding. This divergence may be "epigenetic" — involving
easily changeable control elements that alter the expression of genes,
but do not affect their DNA sequence.
An epigenetic theory of speciation is attractive to some researchers
because the gradual accumulation of genetic mutations that is needed to
produce distinct species is considered by some to be too slow to
explain the rapid emergence of distinct species.
By conducting a complex series of "backcrosses" between the two
Peromyscus species and their resulting hybrids, Tilghman and her
colleagues sought to determine whether disruption of imprinting affects
survival of the offspring.
An analysis of the animals resulting from such backcrosses revealed
that the inviability of the hybrids was partly due to two genes — one
on the X chromosome of the polionotus species that is expressed
only when inherited from the mother, and the other on an autosomal
chromosome of the maniculatus species that is expressed only
when inherited from the father. The scientists localized these genes to
two specific regions, or loci, of the mouse chromosomes and found
evidence that the two loci directly interacted to create the genetic
incompatibility that was reflected in the abnormal growth of the hybrid
mice.
The scientists' experimental crosses also revealed that the severity
of abnormal overgrowth correlated directly with the disruption of
normal imprinting of a number of genes in the animals.
"In other words, the more overgrown the embryos were, the greater
the imprinting disruption," said Paul B. Vrana, the article's lead
author. "We found that the two phenomena were highly correlated."
Another important point of this article, Vrana said, is that
imprinting signals diverge between species. "We showed that the
differences in phenotypes seen in hybrids that are affected by the
parent of origin — for example overgrown animals versus small —
really do have something to do with imprinting."
"In explaining mechanisms of speciation, I believe that people have
tended to ignore imprinting, or parent-of-origin effects, simply
because until fairly recently we didn't have good genetic explanations
for most of them," he said. "However, more explanations of imprinting
are now appearing in the literature for both plants and animals. And
these are showing that speciation can be produced not only because of
incompatible genetic interactions, but also because of epigenetic
control of gene expression, like imprinting."
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