Origin of life: Which came first?
An experiment in recreating primordial proteins solves a long-standing
riddle

Date:
June 22, 2020
Source:
Weizmann Institute of Science
Summary:
What did the very first proteins look like -- those that appeared
on Earth around 3.7 billion years ago? Prof. Scientists have
reconstructed protein sequences that may well resemble those
ancestors of modern proteins, and their research suggests a way
that these primitive proteins could have progressed to forming
living cells.



FULL STORY ========================================================================== [Amino acid molecular | Credit: (c) Sergey Tarasov / stock.adobe.com]
Amino acid molecular models (stock image).

Credit: (c) Sergey Tarasov / stock.adobe.com [Amino acid molecular |
Credit: (c) Sergey Tarasov / stock.adobe.com] Amino acid molecular models (stock image).

Credit: (c) Sergey Tarasov / stock.adobe.com Close What did the very
first proteins look like -- those that appeared on Earth around 3.7
billion years ago? Prof. Dan Tawfik of the Weizmann Institute of Science
and Prof. Norman Metanis of the Hebrew University of Jerusalem have reconstructed protein sequences that may well resemble those ancestors of modern proteins, and their research suggests a way that these primitive proteins could have progressed to forming living cells. Their findings
were published in the Proceedings of the National Academy of Sciences
(PNAS).


==========================================================================
The proteins encoded in a cell's genetic material are the screws,
springs and cogs of a living cell -- all of its moving parts. But the
first proteins, we assume, appeared well before cells and thus life as
we know it. Modern proteins are made of 20 different amino acids, all
of them essential to protein- building, and all arranged in the form
of a polymer -- a long, chain-like molecule -- in which the placement
of each amino acid is crucial to the protein's function. But there is a
paradox in thinking about how the earliest proteins arose. Because the
amino acids needed to make proteins are themselves produced by other
proteins -- enzymes. It's a chicken-and-egg kind of question, and it
has only been partially answered until now.

Scientists believe that the very first true proteins materialized from
shorter protein segments called peptides. The peptides would have been
sticky assemblies of the amino acids that were spontaneously created
in the primeval chemical soup; the short peptides would have then
bound to one another, over time producing a protein capable of some
sort of action. The spontaneous generation of amino acids had already
been demonstrated in 1952, in the famous experiment by Miller and Urey,
in which they replicated the conditions thought to exist on Earth prior
to life and added energy like that which could come from lightning or volcanoes. Showing amino acids could, under the right conditions, form
without help from enzymes or any other mechanism in a living organism
suggested that amino acids were the "egg" that preceded the enzyme
"chicken." Tawfik, who is in the Institute's Biomolecular Sciences
Department, says that is all well and good, "but one vital type of amino
acid has been missing from that experiment and every experiment that
followed in its wake: amino acids like arginine and lysine that carry a positive electric charge." These amino acids are particularly important
to modern proteins, as they interact with DNA and RNA, both of which
carry net negative charges. RNA is today presumed to be the original
molecule that could both carry information and make copies of itself,
so contact with positively-charged amino acids would theoretically be
necessary for further steps in the development of living cells to occur.

But there was one positively-charged amino acid that appeared in the
Miller- Urey experiments, an amino acid called ornithine that is today
found as an intermediate step in arginine production, but is not, itself,
used to build proteins. The research team asked: What if ornithine was
the missing amino acid in those ancestral proteins? They designed an
original experiment to test this hypothesis.

The scientists began with a relatively simple protein from a family
that binds to DNA and RNA, applying phylogenetic methods to infer the
sequence of the ancestral protein. This protein would have been rich
in positive charges -- 14 of the 64 amino acids being either arginine
or lysine. Next, they created synthetic proteins in which ornithine
replaced these as the positive charge carrier.

The ornithine-based proteins bound to DNA, but weakly. In Metanis'
lab, however, the researchers found that simple chemical reactions
could convert ornithine to arginine. And these chemical reactions
occurred under those conditions assumed to have prevailed on Earth at
the time the first proteins would have appeared. As more and more of the ornithine was converted to arginine, the proteins came more and more to resemble modern proteins, and to bind to DNA in a way that was stronger
and more selective.

The scientists also discovered that in the presence of RNA, that
the ancient form of the peptide engaged in phase separation (like
oil drops in water) -- a step that can then lead to self-assembly and "departmentalization." And this, says Tawfik, suggests that such proteins, together with RNA, could form proto- cells, from which true living cells
might have evolved.

Prof. Dan Tawfik is the incumbent of the Nella and Leon Benoziyo
Professorial Chair.


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


========================================================================== Journal Reference:
1. Liam M. Longo, Dragana Despotović, Orit Weil-Ktorza, Matthew J.

Walker, Jagoda Jabłońska, Yael Fridmann-Sirkis, Gabriele
Varani, Norman Metanis, Dan S. Tawfik. Primordial emergence of a
nucleic acid-binding protein via phase separation and statistical
ornithine-to- arginine conversion. Proceedings of the National
Academy of Sciences, 2020; 202001989 DOI: 10.1073/pnas.2001989117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200622095023.htm

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