Survival of the fit-ish

Date:
August 17, 2020
Source:
Stowers Institute for Medical Research
Summary:
It can be hard to dispute the common adage 'survival of the
fittest'.

After all, 'most of the genes in the genome are there because
they're doing something good,' says a researcher. But, she says,
'others are just there because they've figured out a way to
be there.'


FULL STORY ==========================================================================
It can be hard to dispute the common adage 'survival of the
fittest'. After all, "most of the genes in the genome are there because
they're doing something good," says Sarah Zanders, PhD, assistant
investigator at the Stowers Institute for Medical Research. But, she says, "others are just there because they've figured out a way to be there."

==========================================================================
The conventional understanding of evolution is that genes encoding a
beneficial function are the most frequently transmitted, which ensures
that the fittest organisms -- the ones that have traits most favorable
for their environment - - survive. Less known is the fact that there
exist parasitic gene elements within an organism that are doing just
the opposite.

"The way one could think of it is that the genome is like a society,"
explains Zanders. "Within that society, there are individuals who derive
their living from doing good things and making valuable contributions. But there are others who don't contribute in beneficial ways and are actually harmful to society," explains Zanders.

The Zanders Lab studies parasitic genes in Schizosaccharomyces pombe,
a species of fission yeast sometimes found in the popular fermented tea
drink kombucha.

Because of its simplicity and fast generation times, S. pombe is a highly tractable system for studying parasitic gene elements, particularly a
class known as meiotic drivers. Instead of conferring a benefit to their
host, meiotic drivers confer distinct disadvantages to their host, in
order to bias their own perpetuation. One method of doing so, employed
by the wtf meiotic drive genes, is through selective poisoning of cells
in meiosis.

Meiosis is the process of cell division through which sexually-reproducing organisms form gametes -- such as egg and sperm cells in humans,
or spores in yeast -- to propagate the next generation. Normally,
this process results in gametes that inherit one of two copies of each chromosome carried by the parent cell, and each copy is transmitted to
gametes at an equal rate. Meiotic drivers, however, short-circuit this
law of Mendelian segregation.

"Usually all the alleles -- or variants of a particular gene -- get a
fair chance, and natural selection can pick the best ones," explains
Zanders. "But alleles that are meiotic drivers select themselves even
if they're not the best option. And they're never the best option."
In a paper published online August 13, 2020, in eLife, members of the
Zanders lab explain how it could be possible that meiotic drivers persist
in the population, even as they kill off many would-be hosts. It turns
out that S.

pombe can employ variants of other genes to help suppress the negative
effect of meiotic drivers, albeit at a cost to fitness.



========================================================================== Usually, to propagate laboratory strains of S. pombe, they are
inbred. "When you outcross two isolates that are almost identical, they
produce almost no progeny," explains first author Mari'a Ange'lica Bravo Nu'n~ez, PhD, who was involved in the identification of the wtf genes,
and who did this work in the Zanders Lab as a predoctoral researcher at
the Graduate School of the Stowers Institute. "This suggested there might
be some type of competition at play." Bravo Nu'n~ez and colleagues used
this reasoning to seek out genes that could be in conflict in similar,
but non-identical, genomes of S. pombe. The central experimental design
of the current work involved outcrossing of S. pombe isolates that are
over 99% identical.

"Outcrossing can have many advantages," says Bravo Nu'n~ez, such as
providing a normal allele of a gene to rescue the effect of a mutant
allele. "But the meiotic drive genes that we study actually exert their deleterious effect in the heterozygous scenario, where the alleles of
a gene are not the same." One illuminating experiment they did was to
compare outcomes of inbred and outcrossed S. pombe isolates in a genetic background containing a mutation in rec12, which is a gene that promotes
proper chromosome segregation.

"Rec12 usually promotes fertility," says Bravo Nu'n~ez. "When we removed
rec12 function, the numbers of viable spores decreased, but only in
the inbred scenario. The relative numbers of viable spores didn't really decrease in the outcrossed scenario." Moreover, of the viable spores, they found that survival was biased towards atypical gamete products, resulting
from mis-segregation and unequal crossover of paired chromosomes. In
other words, surviving spores contained the maximal number of meiotic
drivers, sometimes due to inheriting an extra chromosome. This finding
was surprising because extra chromosomes are usually considered very
harmful. In humans, for instance, extra or missing chromosomes can lead
to inviable gametes, severe birth defects, or infertility.

"When you have heterozygosity of wtf genes, making a mutation in the
rec12 gene is relatively good for the organism, because that's just what
has to happen in order to not kill all the progeny," says Bravo Nu'n~ez.



==========================================================================
"We think of rec12 as this gene that's really important for fertility," explains Zanders. "But the situation is totally different when there is outcrossing. Having rec12 doesn't actually help at all, because the yeast
is better off making gametes that do not result from proper chromosome segregation. This is just one example of the power of meiotic drivers
to change the landscape of meiosis. Fundamentally, what is 'good' for
the organism has changed." "Having that extra chromosome is not good,
and the yeast colonies look unusual, small, and irregular. But after
they continue to grow for a while, the cells lose that extra chromosome
and then they can thrive as haploids. So, this step is actually just temporary," says Bravo Nu'n~ez.

Precisely because meiotic drivers exert their influence in a heterozygous scenario, they are easy to miss. "There are many flavors of meiotic
drive. Some forms of meiotic drive are hard to measure experimentally
because the bias is so subtle," says Zanders. "We're not the first
to study meiotic drivers in depth. We just have a better model system
now, so we can make more progress faster." "Drive systems tend to be repetitive, and you can usually find them in various copies in genomes,"
says Bravo Nu'n~ez. "They have, in many cases, already been found in
other systems, such as fungi, mice, and fruit flies, but are not yet
fully characterized." The study of meiotic drivers in S. pombe "will
hopefully guide future research to understand other drive systems."
"Humans certainly have meiotic drive genes. Whether or not they have
meiotic drive genes of the gamete-killing type is unclear," says
Zanders. "Meiotic drive has likely affected the evolution of human
centromeres, which are regions of chromosomes that are very important
for proper chromosome segregation.

Certain chromosome fusions exhibit meiotic drive in humans, as do
sequences that are involved in DNA recombination. We're going to continue focusing on these and other parasitic gene elements, their strategies, and their effects." Other coauthors of this work include Ibrahim M. Sabbarini
and Lauren E. Eide from the Stowers Institute and Robert L. Unckless,
PhD, from the University of Kansas.

This work was funded in part by the Stowers Institute for Medical
Research, March of Dimes Foundation Basil O'Connor Starter Scholar
Research Award (5- FY18-58 to SEZ), Searle Scholar Award (to SEZ), and
National Institutes of Health (National Institute of General Medical
Sciences awards R00GM114436 and DP2GM132936 to SEZ and National Cancer Institute award F99CA234523 to MABN).

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes
of Health.


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


========================================================================== Journal Reference:
1. Mari'a Ange'lica Bravo Nu'n~ez, Ibrahim M Sabbarini, Lauren E Eide,
Robert L Unckless, Sarah E Zanders. Atypical meiosis can be
adaptive in outcrossed Schizosaccharomyces pombe due to wtf meiotic
drivers. eLife, 2020; 9 DOI: 10.7554/eLife.57936 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200817123109.htm

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