Biologists trace plants' steady mitochondrial genomes to a gene found in viruses, bacteria

Date:
July 9, 2020
Source:
Colorado State University
Summary:
Biologists have traced the stability of plant mitochondrial
genomes to a particular gene - MSH1 - that plants have but animals
don't. Their experiments could lend insight into why animal
mitochondrial genomes tend to mutate.



FULL STORY ==========================================================================
One could say that mitochondria, the energy-producing organelles inside
every human cell, dance to their own beat. After all, they have their
own genome - a set of DNA-containing chromosomes -- completely separate
from the genome of the cell's nucleus.


========================================================================== Mitochondria are essential to life because they power the cell's
biochemical reactions, but they make a lot of missteps -- that is,
their genomes do. Human mitochondrial genomes are notoriously prone
to mutation, which is why so many genetic disorders -- from diabetes
mellitus to mitochondrial myopathy -- are linked to malfunctioning genes
in this organelle.

Seeking to understand why human mitochondrial genomes mess up so much,
Colorado State University biologist Dan Sloan thinks we have a lot to
learn from our very distant evolutionary cousins -- plants. Like us,
plants maintain a separate mitochondrial genome, but unlike us, plant mitochondrial genomes have some of the slowest known mutation rates
of any living thing -- about one mutation at each DNA position in a
billion years. Just how they keep their genetic sequences on lockdown,
while we don't, has long been a mystery for many biologists.

Sloan is funded by a grant from the National Institutes of Health to investigate why plants have such stable mitochondrial genomes, and his
lab has recently come across a tantalizing lead. They have traced this stability to a particular gene -- MSH1 -- that plants have but animals (including us) don't.

Their experiments, described in Proceedings of the National Academy
of Sciences, could lend insight into why animal mitochondrial genomes
tend to mutate, possibly leading to breakthrough therapies to prevent
such mutations.

"Understanding how some systems have been able to maintain these really accurate, low mutation rates, sets up the opportunity for understanding
the flip side of the coin -- how it is that humans suffer such high mitochondrial mutation rates," said Sloan, associate professor in the Department of Biology.

"It's not as simple as just the nasty chemistry going on inside these mitochondrial compartments, as some have thought. It probably comes down
to more differences between organisms' error correction machinery. That's
one of the punchlines that comes out of this research." The researchers
tested several plant genes they thought might be responsible for
mitochondrial genomic stability. They found that disrupting the MSH1
gene in a common plant, Arabidopsis thaliana, led to massive increases in frequency of point mutations and changes to the mitochondrial DNA. MSH1,
it turns out, contains molecular features that may make it able to
recognize mismatches of nucleotide base pairings during the process of
DNA copying. They researchers plan to follow up on this hypothesis in
later studies.

The MSH1 gene exists in plants, but not animals, which offers a good explanation for why human mitochondrial genomes mutate so often. The researchers then asked, where did this gene come from? To find an
answer, undergraduate researcher and paper co-author Connor King set
out to explore the distribution of the gene across the tree of life. He computationally mined nucleotide and protein sequence repositories to
find what species have the gene. He found evidence of the gene not only
in plants but also in many lineages of complex organisms, including single-celled eukaryotic organisms, as well as some prokaryotic and
viral species.

King's analysis raises the possibility that the gene came from so-called
giant viruses that have genomes almost the size of bacteria, and are
much more complex than typical viruses. They may have been shared with
other organisms via an ancient horizontal gene transfer, in which one
species transfers DNA into another.

"Connor's results pretty clearly tell us that this gene has been
transferred around different parts of the tree of life," Sloan said. This insight would be consistent with the idea that some organisms manage to
borrow machinery from viruses and replace it with their own.

The study was made possible by advanced DNA sequencing, in which huge
amounts of DNA can be mined to find very rare mutations. A key enabling innovation was led by graduate student and co-author Gus Waneka, who
customized a technique called duplex sequencing to increase its accuracy
within the margin of error the team needed to draw their conclusions.


========================================================================== Story Source: Materials provided by Colorado_State_University. Original
written by Anne Manning. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Zhiqiang Wu, Gus Waneka, Amanda K. Broz, Connor R. King, Daniel
B. Sloan.

MSH1 is required for maintenance of the low mutation rates in plant
mitochondrial and plastid genomes. Proceedings of the National
Academy of Sciences, 2020; 202001998 DOI: 10.1073/pnas.2001998117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200709150118.htm

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