Evolution News - Evolution Before Abiogenesis

Fig. 1.
Templated ligation of random sequence DNA 12-mers. (A) Before cells evolved, the first ribozymes were thought to perform basic cell functions. In the exponentially vast sequence space, spontaneous emergence of a functional ribozyme is highly unlikely, therefore preselection mechanisms were likely necessary. (B) In our experiment, DNA strands hybridize at low temperatures to form three-dimensional complexes that can be ligated and preserved in the high temperature dissociation steps. The system self-selects for sequences with specific ligation site motifs as well as for strands that continue acting as templates. Hairpin sequences are therefore suppressed. (C) Concentration analysis shows progressively longer strands emerging after multiple temperature cycles. The inset (A-red, T-blue) shows that, although 12-mers (88,009 strands) have essentially random sequences (white), various sequence patterns emerge in longer strands (60-mers, 235,913 strands analyzed). (D) Samples subjected to different number (0 to 1,000) of temperature cycles between 75 °C and 33 °C. Concentration quantification is done on PAGE with SYBR poststained DNA.

© 2021 The authors

Did Darwinian evolution begin before life itself? | News - LMU München

News today that research physicists at Ludwig-Maximilians-Universität, München, Germany (LMU) may have solved one of the key questions relating to abiogenesis - how did order begin to emerge from the chaos of random organic chemicals? It appears that this was the result of Darwinian evolution of molecules!

In the words of the LMU New release:

Before life emerged on Earth, many physicochemical processes on our planet were highly chaotic. A plethora of small compounds, and polymers of varying lengths, made up of subunits (such as the bases found in DNA and RNA), were present in every conceivable combination. Before life-like chemical processes could emerge, the level of chaos in these systems had to be reduced. In a new study, LMU physicists led by Dieter Braun show that basic features of simple polymers, together with certain aspects of the prebiotic environment, can give rise to selection processes that reduce disorder.

In common with many researchers in this field, the LMU team placed abiogenesis in "narrow, water-filled chambers within porous volcanic rocks on the sea bottom", in other words in the porous rocks around deep ocean hydrothermal vents.

These studies showed that, in the presence of temperature differences and a convective phenomenon known as the Soret effect, RNA strands could locally be accumulated by several orders of magnitude in a length-dependent manner. “The problem is that the base sequences of the longer molecules that one obtains are totally chaotic“, says Braun. Evolved ribozymes (RNA-based enzymes) have a very specific base sequence that enable the molecules to fold into particular shapes, while the vast majority of oligomers formed on the Early Earth most probably had random sequences. “The total number of possible base sequences, known as the ‘sequence space’, is incredibly large,” says Patrick Kudella, first author of the new report. “This makes it practically impossible to assemble the complex structures characteristic of functional ribozymes or comparable molecules by a purely random process.” This led the LMU team to suspect that the extension of molecules to form larger ‘oligomers’ was subject to some sort of preselection mechanism.

How long-chain molecules are formed.

© LMU

Model system for early oligomers

Since at the time of the Origin of Life there were only a few, very simple physical and chemical processes compared to the sophisticated replication mechanisms of cells, the selection of sequences must be based on the environment and the properties of the oligomers. This is where the research of Braun's group comes in. For catalytic function and stability of oligomers, it is important that they form double strands like the well-known helical structure of DNA. This is an elementary property of many polymers and enables complexes with both double- and single-stranded parts. The single-stranded parts can be reconstructed by two processes. First, by so-called polymerization, in which strands are completed by single bases to form complete double strands. The other is by what is known as ligation. In this process, longer oligomers are joined together. Here, both double-stranded and single-stranded parts are formed, which enable further growth of the oligomer.

“Our experiment starts off with a large number of short DNA strands, and in our model system for early oligomers we use only two complementary bases, adenine and thymine“, says Braun. “We assume that ligation of strands with random sequences leads to the formation of longer strands, whose base sequences are less chaotic.” Braun‘s group then analyzed the sequence mixtures produced in these experiments using a method that is also used in analyzing the human genome. The test confirmed that the sequence entropy, i.e. the degree of disorder or randomness within the sequences recovered, was in fact reduced in these experiments.

Significance

The structure of life emerged from randomness. This is attributed to selection by molecular Darwinian evolution. This study found that random templated ligation led to the simultaneous elongation and sequence selection of oligomers. Product strands showed highly structured sequence motifs which inhibited self-folding and built self-templating reaction networks. By the reduction of the sequence space, the kinetics of duplex formation increased and led to a faster replication through the ligation process. These findings imply that elementary binding properties of nucleotides can lead to an early selection of sequences even before the onset of Darwinian evolution. This suggests that such a simplification of sequence space could result in faster downstream selection for sequence-based function for the origin of life.

Abstract

The central question in the origin of life is to understand how structure can emerge from randomness. The Eigen theory of replication states, for sequences that are copied one base at a time, that the replication fidelity has to surpass an error threshold to avoid that replicated specific sequences become random because of the incorporated replication errors [M. Eigen, Naturwissenschaften 58 (10), 465–523 (1971)]. Here, we showed that linking short oligomers from a random sequence pool in a templated ligation reaction reduced the sequence space of product strands. We started from 12-mer oligonucleotides with two bases in all possible combinations and triggered enzymatic ligation under temperature cycles. Surprisingly, we found the robust creation of long, highly structured sequences with low entropy. At the ligation site, complementary and alternating sequence patterns developed. However, between the ligation sites, we found either an A-rich or a T-rich sequence within a single oligonucleotide. Our modeling suggests that avoidance of hairpins was the likely cause for these two complementary sequence pools. What emerged was a network of complementary sequences that acted both as templates and substrates of the reaction. This self-selecting ligation reaction could be restarted by only a few majority sequences. The findings showed that replication by random templated ligation from a random sequence input will lead to a highly structured, long, and nonrandom sequence pool. This is a favorable starting point for a subsequent Darwinian evolution searching for higher catalytic functions in an RNA world scenario.

Kudella, Patrick W.; Tkachenko, Alexei V.; Salditt, Annalena; Maslov, Sergei; Braun, Dieter
Structured sequences emerge from random pool when replicated by templated ligation
Proceedings of the National Academy of Sciences Feb 2021, 118 (8) e2018830118; DOI: 10.1073/pnas.2018830118

Copyright: © 2021 The authors. Published by the National Academy of Sciences.
Open access
Reprinted under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).

Emergence of life from chaos

The researchers were also able to identify the causes of this ‘self-generated’ order. They found that the majority of sequences obtained fell into two classes – with base compositions of either 70 % adenine and 30 % thymine, or vice versa. “With a significantly larger proportion of one of the two bases, the strand cannot fold onto itself and remains as a reaction partner for the ligation”, Braun explains. Thus, hardly any strands with half of each of the two bases are formed in the reaction. "We also see how small distortions in the composition of the short DNA pool leave distinct position-dependent motif patterns, especially in long product strands," Braun says. The result surprised the researchers, because a strand of just two different bases with a specific base ratio has limited ways to differentiate from each other. "Only special algorithms can detect such amazing details," says Annalena Salditt, co-author of the study.

The experiments show that the simplest and most fundamental characteristics of oligomers and their environment can provide the basis for selective processes. Even in a simplified model system, various selection mechanisms can come into play, which have an impact on strand growth at different length scales, and are the results of different combinations of factors. According to Braun, these selection mechanisms were a prerequisite for the formation of catalytically active complexes such as ribozymes, and therefore played an important role in the emergence of life from chaos.

We are used to thinking of evolution by Darwinian natural selection as applying to living systems, but this paper shows how it may well have applied to the precursor chemicals which eventually resulted in the complex chemicals and the order necessary for self-sustaining early cells to get started. Darwinian evolution will occur in any system where there is imperfect, inherited replication and some environmentally-dependent mechanism for selection which gives some variants an advantage over others, in that environment. In this case, the ability to self-catalyse was one such advantage which resulted in the natural emergence of order from chaos.

No magic was needed.

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