The mystery of why life uses molecules with specific orientations has deepened with a NASA-funded discovery that RNA — a key molecule thought to have potentially held the instructions for life before DNA emerged — can favor making the building blocks of proteins in either the left-hand or the right-hand orientation. Resolving this mystery could provide clues to the origin of life. The findings appear in research recently published in Nature Communications.
Proteins are the workhorse molecules of
life, used in everything from structures like hair to enzymes (catalysts that
speed up or regulate chemical reactions). Just as the 26 letters of the
alphabet are arranged in limitless combinations to make words, life uses 20
different amino acid building blocks in a huge variety of arrangements to make
millions of different proteins. Some amino acid molecules can be built in two
ways, such that mirror-image versions exist, like your hands, and life uses the
left-handed variety of these amino acids. Although life based on right-handed
amino acids would presumably work fine, the two mirror images are rarely mixed
in biology, a characteristic of life called homochirality. It is a mystery to
scientists why life chose the left-handed variety over the right-handed one.
A diagram of left-handed and right-handed versions of
the amino acid isovaline, found in the Murchison meteorite.
NASA
DNA (deoxyribonucleic acid) is the molecule that holds the instructions for
building and running a living organism. However, DNA is complex and
specialized; it “subcontracts” the work of reading the instructions to RNA
(ribonucleic acid) molecules and building proteins to ribosome molecules. DNA’s
specialization and complexity lead scientists to think that something simpler
should have preceded it billions of years ago during the early evolution of
life. A leading candidate for this is RNA, which can both store genetic
information and build proteins. The hypothesis that RNA may have preceded DNA
is called the “RNA world” hypothesis.
If the RNA world proposition is
correct, then perhaps something about RNA caused it to favor building
left-handed proteins over right-handed ones. However, the new work did not
support this idea, deepening the mystery of why life went with left-handed proteins.
The experiment tested RNA molecules
that act like enzymes to build proteins, called ribozymes. “The experiment
demonstrated that ribozymes can favor either left- or right-handed amino acids,
indicating that RNA worlds, in general, would not necessarily have a strong
bias for the form of amino acids we observe in biology now,” said Irene Chen,
of the University of California, Los Angeles (UCLA) Samueli School of
Engineering, corresponding author of the Nature
Communications paper.
In the experiment, the researchers
simulated what could have been early-Earth conditions of the RNA world. They
incubated a solution containing ribozymes and amino acid precursors to see the
relative percentages of the right-handed and left-handed amino acid,
phenylalanine, that it would help produce. They tested 15 different ribozyme
combinations and found that ribozymes can favor either left-handed or
right-handed amino acids. This suggested that RNA did not initially have a
predisposed chemical bias for one form of amino acids. This lack of preference
challenges the notion that early life was predisposed to select
left-handed-amino acids, which dominate in modern proteins.
“The findings suggest that life’s
eventual homochirality might not be a result of chemical determinism but could
have emerged through later evolutionary pressures,” said co-author Alberto
Vázquez-Salazar, a UCLA postdoctoral scholar and member of Chen’s
research group.
Earth’s prebiotic history lies
beyond the oldest part of the fossil record, which has been erased by plate
tectonics, the slow churning of Earth’s crust. During that time, the planet was
likely bombarded by asteroids, which may have delivered some of life’s building
blocks, such as amino acids. In parallel to chemical experiments, other
origin-of-life researchers have been looking at molecular evidence from
meteorites and asteroids.
“Understanding the chemical
properties of life helps us know what to look for in our search for life across
the solar system,” said co-author Jason Dworkin, senior scientist for
astrobiology at NASA’s Goddard Space Flight Center in Greenbelt, Maryland, and
director of Goddard’s Astrobiology
Analytical Laboratory.
Dworkin is the project scientist on
NASA’s OSIRIS-REx
mission, which
extracted samples from the asteroid Bennu and delivered them to Earth last year
for further study.
“We are analyzing OSIRIS-REx samples for the chirality (handedness) of individual
amino acids, and in the future, samples
from Mars will
also be tested in laboratories for evidence of life including ribozymes and
proteins,” said Dworkin.
The research was supported by grants from NASA, the Simons Foundation Collaboration on the Origin of Life, and the National Science Foundation. Vázquez-Salazar acknowledges support through the NASA Postdoctoral Program, which is administered by Oak Ridge Associated Universities under contract with NASA.
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