Life should be redefined

Zheng Liu

doi:10.12688/f1000research.151912.1

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Opinion Article

Life should be redefined

[version 1; peer review: 1 approved, 1 approved with reservations]

Zheng Liu

PUBLISHED 03 Jul 2024

Author details Author details

College of Laboratory Medicine, Guilin Medical University, Guilin, China

Zheng Liu
Roles: Conceptualization, Funding Acquisition, Investigation, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Understanding the nature of life and its propensity for reproduction has long been a question that humans aspire to answer. Reproduction, a defining characteristic of life, fundamentally involves the replication of genetic material, be it DNA or RNA. The driving force behind this replication process has always intrigued scientists. In recent years, theories involving selfish genes, the RNA world, and entropic forces have been proposed by some scholars. These theories seem to suggest that life, as we know it, exists solely in Earth’s environment and is based on a single type of genetic material, either DNA or RNA. However, if we broaden our definition of life to include any replicable molecules, we might be able to transcend traditional thought. This could potentially enhance our understanding of the impetus behind DNA replication and provide deeper insights into the essence of life.

Keywords

DNA replication, reproduction, RNA world, entropic forces, self-replicating molecules

Corresponding author: Zheng Liu

Competing interests: No competing interests were disclosed.

Grant information: The study was supported by the National Natural Science Foundation of China (No. 32260175), Natural Science Foundation of Guangxi Province (2018JJA140045) and Guangxi Science and Technology Base and Special Fund for Talents (2018AD19267).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2024 Liu Z. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Liu Z. Life should be redefined [version 1; peer review: 1 approved, 1 approved with reservations]. F1000Research 2024, 13:736 (https://doi.org/10.12688/f1000research.151912.1) First published: 03 Jul 2024, 13:736 (https://doi.org/10.12688/f1000research.151912.1) Latest published: 20 Sep 2024, 13:736 (https://doi.org/10.12688/f1000research.151912.2)

Introduction

The quest for understanding the existence of life has always captivated people. Currently, it’s challenging to define what life is. Traditionally, Life is defined as an extension of being into the next generation and into the next species in evolutionary time (Chatterjee, 2023). Reproduction, the process of passing on genetic material (DNA or RNA) to the next generation, is a fundamental characteristic of life. This phenomenon prompts the question: why is the replication of DNA or RNA necessary for life and what drive DNA or RNA replication? Over the years, scientists have deepened their understanding of life. Some have proposed the theory of selfish genes (Noble and Noble, 2022), while others argue that RNA is the origin of life (Higgs and Lehman, 2015). A particularly innovative perspective comes from Professor Jeremy England, who posits that entropic forces drive the replication of DNA or RNA (England, 2013). His theory, grounded in the second law of physics, suggests that life arises from the increase in the universe’s entropy. This provides a physical explanation for the reproduction and continuation of life. Building on these theoretical foundations, I think the life and genetic materials should be redefined. Given that DNA or RNA, as genetic material, can replicate and generate life, I hypothesize that any molecules with replication capabilities, regardless of their environment, could potentially evolve into life. This speculation opens up possibilities for the discovery of new life forms in the universe.

The expectation for reproduction of organisms

Why is there such a vast diversity of life on Earth? The prevailing understanding is that given varying environmental pressures and ample time, a single species can evolve into distinct species. Each species has a natural desire to reproduce and pass on its genes. As Charles Darwin elucidated, individuals possessing traits that better suit their environment have a higher likelihood of reproducing. This allows them to pass on these advantageous traits to their offspring, thereby enhancing the organism’s reproductive success and allowing the organism to reproduce more. Over time, this process results in the evolution of species that are well-adapted to their specific environments. The innate drive to survive and reproduce is fundamental to the perpetuation and diversity of life on Earth. But what exactly is the purpose behind the reproduction of species? Humans have established complex societies, systems of relationships and norms, to fulfil their social, emotional, and cultural needs. Naturally, human reproduction encompasses these needs, including sexual maturation, social support, and the continuation of the family line. In today’s world, there is no doubt that social and emotional needs have become paramount. However, these needs are not present in viruses, bacteria, or insects. Although viruses and bacteria seem to lack self-consciousness, they still carry out self-replication. A fascinating example is the male mayfly, which has a lifespan of only 24 hours (Araújo et al., 2021). Its sole purpose from birth is to mate. What is the objective of this replication in bacteria and viruses and what drives male mayflies to behave in such a way?

Selfish genes drive reproduction

One theory suggests that genes choose us, and they are selfish (Gardner and Welch, 2011). In his book, ‘The Selfish Gene’, Richard Dawkins posits that genes, rather than individuals or species, are the primary units of selection in evolution. Consequently, genes have propelled the reproduction of all species. According to this theory, genes are the fundamental unit of natural selection, acting in a manner that ensures their own survival. Organisms serve as carriers of these genes, with reproduction being the ultimate goal (Figure 1). Reproduction is the prize for living organism with or without self-consciousness. Numerous instances of this theory are evident in nature, and recent studies have further validated it. A study found that individuals with specific variants of the ERAP2 gene had a higher survival rate during the Black Death, a catastrophic pandemic in the 14^th century (Klunk et al., 2022). This pandemic, from another perspective, is that ERAP2 gene with specific variants, selectively replicated itself within certain individuals. Such events have recurred throughout human history, exerting substantial selective pressure on the human population. This altered the prevalence of certain genetic variants, thereby influencing our disease susceptibility today. From this perspective, it appears as though the ERAP2 gene with specific variants is driven by its survival instinct. However, this theory does not address the question of why genes, despite their lack of self-consciousness, need to replicate and ensure their survival. In other words, what is the purpose of gene replication?

Figure 1. Entropic forces drive the evolution, leading to the generation of new life forms.

On Earth, inorganic molecules capable of self-replication spontaneously synthesize organic molecules, including RNA. Influenced by the entropic forces, RNA serves as the genetic material, leading to the emergence of life, irrespective of whether the organisms possess self-consciousness. In environments distinct from Earth, any molecules with self-replication capabilities could potentially evolve into genetic material, thereby initiating new forms of life.

Life begins with RNA

In order to address the aforementioned questions, it is essential to determine what the first gene or genetic material on Earth was and understand how it initiated replication. The RNA world hypothesis suggests that life on Earth have begun with a simple self-replicating RNA molecule, with DNA only appearing later as a result of RNA evolution. Gerald Joyce team discovered that a highly evolved RNA polymerase ribozyme has the ability to function as a reverse transcriptase (Samanta and Joyce, 2017). This reverse transcriptase ribozyme can incorporate all four types of dNTPs and can produce products containing up to 32 deoxynucleotides. Recently, significant progress has been made by the team led by Clemens Richert. They managed to replicate RNA sequences of up to 12 nucleotides in a dilute aqueous solution of an unactivated dinucleotide, without the involvement of any enzymes (Welsch et al., 2023). The RNA world hypothesis offers a persuasive explanation for the early stages of life on Earth. However, is RNA an organic molecule that can be directly synthesized from inorganic substances? The Miller-Urey experiment in 1953 was provided evidence that essential organic molecules, fundamental to life, could be synthesized from inorganic substances. In fact, scientists have developed more methods in recent years to synthesize organic molecules from hydrogen and oxygen under different conditions (Hudson et al., 2020). Studies have demonstrated that all four of RNA’s major components can be efficiently assembled from simple chemicals under certain conditions (Figure 1). A paper published in Science presents a straightforward chemical pathway to the formation of ribonucleotides (Becker et al., 2016). These studies underscore the remarkable ability of the natural environment to transform simple inorganic molecules into complex organic ones, such as RNA, a key characteristic of life on Earth. It suggests that the emergence of life could be a random event in nature, rather than being designed. However, what drives RNA to replicate itself?

Entropic forces drive life

Jeremy England, a professor at Massachusetts Institute of Technology, has put forth a theory suggesting that life arises because the principle of increasing entropy compels matter to adopt life-like physical properties (England, 2015). It would suggest that the replication of genes is driven by entropic forces (Figure 1). This theory has been employed to elucidate the impetus behind evolution and the replication of DNA/RNA. DNA/RNA molecules prefer to be in their lowest energy conformation (the resting position with high entropy). Replication of DNA or RNA is a process that facilitates the attainment of this state. Interestingly, this theory is a manifestation of the renowned Big Chill hypothesis (or the heat death of the universe) in the context of human evolution. The Big Chill hypothesis posits that all entities in the universe are transitioning from a state of uniform high energy to one of high entropy based on the second law of thermodynamics (Fleck, 2023). Therefore, it can be inferred that every living organism will attain a state of high entropy. Molecules with high entropy are both disordered and disorganized. A study discovered that an increase in entropy leads to a more random replication process, potentially resulting in a higher rate of errors or mutations (Arias-Gonzalez., 2012). Actually, gene mutations are essential for the survival of genes under stress. If a mutation provides an organism with an environmental advantage, that organism has a higher likelihood of survival and reproduction. This phenomenon is evident in the continuous mutation of the SARS-CoV-2 virus as it attempts to coexist with humans (Markov et al., 2023).

RNA and DNA are not the only genetic materials

If all the theories mentioned above are proven correct, it leads us to several intriguing questions. Why is life, as we know it, only discovered on Earth so far? To date, there are no known types of genetic material fundamentally different from DNA and RNA. Since anywhere in the universe will transit from a state of low entropy to high entropy, does this imply that only Earth’s environment is suitable for DNA/RNA replication? In other words, does life in the universe require an environment similar to Earth’s to exist? If we assume that the only genetic material for life is DNA or RNA, then it implies that there is only one form of life in the universe, akin to life on Earth. It suggests that only another planet with similar conditions - air, water, temperature, pressure, and so on - could give rise to DNA or RNA, and subsequently, organisms resembling those on Earth. Do we increasingly believe that there is only life on Earth in the universe, or that only environments similar to Earth can produce life? Moreover, life has only one form, which is a living organism with DNA or RNA as genetic material. I disagree with this viewpoint. This perspective is inherently flawed as it habitually considers DNA and RNA as the sole genetic materials. The crux of the matter is that DNA or RNA may be the only genetic materials suitable for Earth’s environment.

Any molecules with self-replicating ability can be genetic material

Perhaps a shift in our perspective could provide a better answer to this question. We could redefine the genetic material of life (or living organisms) as any molecules capable of self-replication, not limited to DNA or RNA (Figure 1). In this way, life needs to be redefined. Actually, self-replicate has been seen in very different looking chemical systems, for example in rotaxanes, a self-assembling rotaxane that can replicate itself discovered by the scientists (Tamara et al., 2015). Ignacio Colomer et al. discovered a self-replicator consists of a system of small molecules composed of hydrogen and carbon (Colomer et al., 2018). This process of self-replication could occur anywhere in the universe, which encompasses a vast range of environments distinct from Earth. For instance, envision this process taking place in an atmosphere with a temperature of -63 degrees Celsius, a pressure of 600 Pa, and a composition of 95% carbon dioxide - conditions naturally found on Mars. Currently, the laboratory possesses the capability to simulate the self-replication of substances under such conditions. Actually, Schulze-Makuch et al., has already proposed alien life could be based on different chemistries, solvents, and energy sources (Schulze-Makuch and Irwin, 2006). Given sufficient time, these simple organic molecules, capable of self-replication, could give rise to other forms of life, similar to the original genetic material RNA on Earth. In other words, the genetic material of life elsewhere in the universe may not necessarily be DNA or RNA, as these replicable molecules could potentially form other new life forms.

Conclusions

This paper presents a novel opinion by reviewing recent studies and theories concerning the biological reproduction, drawing from the fields of biology (with a focus on theories of selfish genes and the RNA world), physics (specifically the second law of thermodynamics and entropy theory), and chemistry (emphasizing self-replicating systems). It suggests that molecules capable of self-replication may, under certain conditions, evolve into various forms of life. This perspective represents a departure from traditional concepts that identify DNA and RNA as the sole genetic materials. It provides a new insight into the origins and implications of life’s existence in the universe, providing a theoretical basis for searching for other diverse forms of life in the universe.

Ethical approval and consent

Ethical approval and consent were not required.

Data availability

No data are associated with this article.

References

Araújo VA, Dias LG, Serrão JE: Rapid and efficient mating in mayflies (Ephemeroptera): morphological and reproductive strategies in primitive winged insects. Naturwissenschaften. 2021; 108(2): 10. PubMed Abstract | Publisher Full Text
Arias-Gonzalez JR: Entropy involved in fidelity of DNA replication. PLoS One. 2012; 7: e42272. PubMed Abstract | Publisher Full Text | Free Full Text
Becker S, Thoma I, Deutsch A, et al.: A high-yielding, strictly regioselective prebiotic purine nucleoside formation pathway. Science. 2016; 352(6287): 833–836. PubMed Abstract | Publisher Full Text
Colomer I, Morrow SM, Fletcher SP: A transient self-assembling self-replicator. Nat. Commun. 2018; 9(1): 2239. PubMed Abstract | Publisher Full Text | Free Full Text
Chatterjee S: Defining Life. From Stardust to First Cells. Cham: Springer; 2023. Publisher Full Text
England JL: Statistical physics of self-replication. J. Chem. Phys. 2013; 139(12): 121923. PubMed Abstract | Publisher Full Text
England JL: Dissipative adaptation in driven self-assembly. Nat. Nanotechnol. 2015; 10(11): 919–923. PubMed Abstract | Publisher Full Text
Fleck R: The Laws of Thermodynamics. Entropy and the Second Law of Thermodynamics. Cham: Springer; 2023. Publisher Full Text
Gardner A, Welch JJ: A formal theory of the selfish gene. J. Evol. Biol. 2011; 24: 1801–1813. PubMed Abstract | Publisher Full Text
Higgs PG, Lehman N: The RNA World: molecular cooperation at the origins of life. Nat. Rev. Genet. 2015; 16(1): 7–17. PubMed Abstract | Publisher Full Text
Hudson R, de Graaf R , Strandoo Rodin M, et al.: CO2 reduction driven by a pH gradient. Proc. Natl. Acad. Sci. USA. 2020; 117(37): 22873–22879. PubMed Abstract | Publisher Full Text | Free Full Text
Klunk J, Vilgalys TP, Demeure CE, et al.: Evolution of immune genes is associated with the Black Death. Nature. 2022; 611: 312–319. PubMed Abstract | Publisher Full Text | Free Full Text
Kosikova T, Hassan NI, Cordes DB, et al.: Orthogonal Recognition Processes Drive the Assembly and Replication of a [2]Rotaxane. J. Am. Chem. Soc. 2015; 137(51): 16074–16083. PubMed Abstract | Publisher Full Text
Markov PV, Ghafari M, Beer M, et al.: The evolution of SARS-CoV-2. Nat. Rev. Microbiol. 2023; 21: 361–379. Publisher Full Text
Noble D, Noble R: Origins and demise of selfish gene theory. Theor Biol Forum. 2022; 115(1-2): 29–43. PubMed Abstract | Publisher Full Text
Samanta B, Joyce GF: A reverse transcriptase ribozyme. elife. 2017; 6: e31153. PubMed Abstract | Publisher Full Text | Free Full Text
Schulze-Makuch D, Irwin LN: The prospect of alien life in exotic forms on other worlds. Naturwissenschaften. 2006; 93(4): 155–172. PubMed Abstract | Publisher Full Text
Welsch F, Kervio E, Tremmel P, et al.: Prolinyl Nucleotides Drive Enzyme-Free Genetic Copying of RNA. Angew. Chem. Int. Ed. Engl. 2023; 62(41): e202307591. PubMed Abstract | Publisher Full Text

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Version 2

VERSION 2 PUBLISHED 03 Jul 2024

Author details Author details

College of Laboratory Medicine, Guilin Medical University, Guilin, China

Zheng Liu
Roles: Conceptualization, Funding Acquisition, Investigation, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The study was supported by the National Natural Science Foundation of China (No. 32260175), Natural Science Foundation of Guangxi Province (2018JJA140045) and Guangxi Science and Technology Base and Special Fund for Talents (2018AD19267).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Article Versions (2)

version 2

Revised

Published: 20 Sep 2024, 13:736

https://doi.org/10.12688/f1000research.151912.2

version 1

Published: 03 Jul 2024, 13:736

https://doi.org/10.12688/f1000research.151912.1

© 2024 Liu Z. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Liu Z. Life should be redefined [version 1; peer review: 1 approved, 1 approved with reservations]. F1000Research 2024, 13:736 (https://doi.org/10.12688/f1000research.151912.1)

NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.

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Open Peer Review

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VERSION 1

PUBLISHED 03 Jul 2024

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Reviewer Report 23 Aug 2024

Kevin S. Lang, University of Minnesota, Saint Paul, MN, USA

Approved with Reservations

https://doi.org/10.5256/f1000research.166604.r299580

This is an intriguing essay that urges for the reassessment of what is considered “life”. The author makes a case for refining definitions of “life” to aid in the pursuit of identifying lifeforms on planets other than Earth. They highlight existing frameworks, such as the selfish gene theory, in the context of replication of biological molecules, suggesting that lifeforms may have some fluidity beyond historical definitions. These ideas have significant value for shaping the perceptions of what life could look like beyond what is observed on Earth. In my opinion the essay could be improved significantly by the following considerations:

The author should consider providing a more explicit suggestion of what they think the definition should be tailored to. For example, is life strictly constrained by the replication of only organic molecules? Could replication of inorganic molecules be considered “life”? This is important as the author highlights that some organic molecules (ie genes) utilize organisms for their own replication. Parallel to this framework, things like limestone could be considered to replicate by utilizing marine life for its replication. Would this then be considered life?
In line with the above comment, would the new definition of life pertain to molecules that template their own replication or self-assembly? The author discusses the generation of biomolecules from inorganic substrates, citing the RNA theory of the origin of life. This is an example of self-assembly. Other examples of this beyond RNA and DNA exist on Earth, for example, prions and viral capsids. The distinction of these molecules is that they don’t necessarily involve templating their own replication. Rather, they drive their own self-assembly from simple substrates to more complex biomolecules. A clearer definition would enhance this essay from being a simple review of existing ideas to proposing a novel definition.
Lastly, the author highlights indexed essays that discuss the relationship between life and entropic forces. However, the way the author discusses the relationship between life and entropy is unclear. For example, the author states that DNA and RNA are in a state of high entropy. This is perplexing, given that these biomolecules are highly ordered, and thus fighting against entropy. Therefore, is the author stating that the new definition of life should be any molecules that are moving to a state of low entropy, and thus, driving themselves away from natural tendency of the 2^nd law of thermodynamics to increase entropy?

In summary, this is an intriguing essay that will benefit by a more explicit definition of what should be considered “life”.

Is the topic of the opinion article discussed accurately in the context of the current literature?

Partly
Are all factual statements correct and adequately supported by citations?

Partly
Are arguments sufficiently supported by evidence from the published literature?

Partly
Are the conclusions drawn balanced and justified on the basis of the presented arguments?

Partly

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: DNA Replication, transcription, translation, microbiology, molecular biology, evolution.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Author Response 20 Sep 2024

Zheng Liu, Guilin Medical University, China

20 Sep 2024

Author Response

Authors' point by point response to the Reviewer comments is as follows -

1.   I have considered this issue while writing my paper, but I have been very cautious. ... Continue reading Authors' point by point response to the Reviewer comments is as follows -

1.   I have considered this issue while writing my paper, but I have been very cautious. I am also concerned that my viewpoint may be too radical and difficult to accept. However, with the help of the F1000Research platform and the opportunity to answer questions, my response is: Yes. Traditional thinking defines life as having certain perceptions or consciousness, such as in humans, animals, and plants. However, the emergence of viruses has challenged this common understanding. A virus is merely a sequence of DNA or RNA, and although it is an organic substance (without consciousness, is it different from inorganic substances?), it constantly replicates and is also a form of life. I believe we can be bolder. In my article, I speculate that inorganic substances capable of self-replication can also be considered life, which is a novel viewpoint in this paper. Regarding the statement 'limestone could be considered to replicate by utilizing marine life,' I disagree because limestone is not self-replicating; its production results from the accumulation of products from marine biological activities. I think it is essential to emphasize self-replication, which involves actively replicating oneself.

2.   This question is very interesting. The main point of the paper is that molecules capable of self-replication can be defined as life, similar to a piece of DNA (virus) that can self-replicate. If a molecule only drives its own self-assembly from simple substrates to more complex biomolecules, I believe this is growth, not replication, and therefore not life. I think the example of prions is also a form of life. Prion protein is coded by the PRNP gene. Prion proteins cannot self-replicate and cannot be considered life. However, while prions are composed of misfolded protein aggregates, they propagate by inducing conformational changes in normal prion proteins (PrP^C) to transform them into the abnormal, disease-causing form (PrP^Sc). The misfolded prion acts as a template, guiding the normal proteins to adopt the abnormal structure, exhibiting characteristics of life. This precisely supports the viewpoint of this paper that any self-replicating molecule, including misfolded prions, can serve as genetic material and ultimately become life. Additionally, I have included examples of prions in the revised version of my paper. Viral capsids are part of a virus and are composed of proteins encoded by viral genes. To my knowledge, I have not seen viral capsids self-replicate. If there were independent viral capsids that could self-replicate (no need for DNA or RNA), I would also define them as life. Thank you very much for your suggestion. I have added a clearer definition of life to my paper in the conclusion section and changed the title to " Life should be redefined: Any molecule with the ability to self-replicate should be considered life ". Additionally, it should be emphasized that self-replication should also include one molecule inducing another molecule to become itself (such as a misfolded prions induce prions).

3.   I believe there may be a misunderstanding. According to England's theory, DNA or RNA molecules exist in a high-energy (low entropy, ordered and organized) state, which makes them ordered. The replication of DNA or RNA molecules progresses towards a lower energy state, ultimately leading to a low-energy (higher entropy, disordered and disorganized). This process is driven by the second law of thermodynamics, which governs the behavior of all matter in the universe, including life. However, an increase in entropy driven by the second law of thermodynamics does not necessarily indicate life; only molecules with active self-replication functions are considered life. The second law of thermodynamics drives all matter in the universe towards disorder and heat death. For example, if a drop of ink is added to a cup of water, the ink will eventually distribute evenly among the water molecules due to the second law of thermodynamics, which is unrelated to life, vice versa. I am very grateful for your suggestions on my paper. I have been contemplating new perspectives on life during this period, and I have added new paragraph accordingly.
Authors' point by point response to the Reviewer comments is as follows -

1.   I have considered this issue while writing my paper, but I have been very cautious. I am also concerned that my viewpoint may be too radical and difficult to accept. However, with the help of the F1000Research platform and the opportunity to answer questions, my response is: Yes. Traditional thinking defines life as having certain perceptions or consciousness, such as in humans, animals, and plants. However, the emergence of viruses has challenged this common understanding. A virus is merely a sequence of DNA or RNA, and although it is an organic substance (without consciousness, is it different from inorganic substances?), it constantly replicates and is also a form of life. I believe we can be bolder. In my article, I speculate that inorganic substances capable of self-replication can also be considered life, which is a novel viewpoint in this paper. Regarding the statement 'limestone could be considered to replicate by utilizing marine life,' I disagree because limestone is not self-replicating; its production results from the accumulation of products from marine biological activities. I think it is essential to emphasize self-replication, which involves actively replicating oneself.

2.   This question is very interesting. The main point of the paper is that molecules capable of self-replication can be defined as life, similar to a piece of DNA (virus) that can self-replicate. If a molecule only drives its own self-assembly from simple substrates to more complex biomolecules, I believe this is growth, not replication, and therefore not life. I think the example of prions is also a form of life. Prion protein is coded by the PRNP gene. Prion proteins cannot self-replicate and cannot be considered life. However, while prions are composed of misfolded protein aggregates, they propagate by inducing conformational changes in normal prion proteins (PrP^C) to transform them into the abnormal, disease-causing form (PrP^Sc). The misfolded prion acts as a template, guiding the normal proteins to adopt the abnormal structure, exhibiting characteristics of life. This precisely supports the viewpoint of this paper that any self-replicating molecule, including misfolded prions, can serve as genetic material and ultimately become life. Additionally, I have included examples of prions in the revised version of my paper. Viral capsids are part of a virus and are composed of proteins encoded by viral genes. To my knowledge, I have not seen viral capsids self-replicate. If there were independent viral capsids that could self-replicate (no need for DNA or RNA), I would also define them as life. Thank you very much for your suggestion. I have added a clearer definition of life to my paper in the conclusion section and changed the title to " Life should be redefined: Any molecule with the ability to self-replicate should be considered life ". Additionally, it should be emphasized that self-replication should also include one molecule inducing another molecule to become itself (such as a misfolded prions induce prions).

3.   I believe there may be a misunderstanding. According to England's theory, DNA or RNA molecules exist in a high-energy (low entropy, ordered and organized) state, which makes them ordered. The replication of DNA or RNA molecules progresses towards a lower energy state, ultimately leading to a low-energy (higher entropy, disordered and disorganized). This process is driven by the second law of thermodynamics, which governs the behavior of all matter in the universe, including life. However, an increase in entropy driven by the second law of thermodynamics does not necessarily indicate life; only molecules with active self-replication functions are considered life. The second law of thermodynamics drives all matter in the universe towards disorder and heat death. For example, if a drop of ink is added to a cup of water, the ink will eventually distribute evenly among the water molecules due to the second law of thermodynamics, which is unrelated to life, vice versa. I am very grateful for your suggestions on my paper. I have been contemplating new perspectives on life during this period, and I have added new paragraph accordingly.
Competing Interests: No competing interests were disclosed. Close
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Author Response 20 Sep 2024

Zheng Liu, Guilin Medical University, China

20 Sep 2024

Author Response

Authors' point by point response to the Reviewer comments is as follows -

1.   I have considered this issue while writing my paper, but I have been very cautious. ... Continue reading Authors' point by point response to the Reviewer comments is as follows -

1.   I have considered this issue while writing my paper, but I have been very cautious. I am also concerned that my viewpoint may be too radical and difficult to accept. However, with the help of the F1000Research platform and the opportunity to answer questions, my response is: Yes. Traditional thinking defines life as having certain perceptions or consciousness, such as in humans, animals, and plants. However, the emergence of viruses has challenged this common understanding. A virus is merely a sequence of DNA or RNA, and although it is an organic substance (without consciousness, is it different from inorganic substances?), it constantly replicates and is also a form of life. I believe we can be bolder. In my article, I speculate that inorganic substances capable of self-replication can also be considered life, which is a novel viewpoint in this paper. Regarding the statement 'limestone could be considered to replicate by utilizing marine life,' I disagree because limestone is not self-replicating; its production results from the accumulation of products from marine biological activities. I think it is essential to emphasize self-replication, which involves actively replicating oneself.

2.   This question is very interesting. The main point of the paper is that molecules capable of self-replication can be defined as life, similar to a piece of DNA (virus) that can self-replicate. If a molecule only drives its own self-assembly from simple substrates to more complex biomolecules, I believe this is growth, not replication, and therefore not life. I think the example of prions is also a form of life. Prion protein is coded by the PRNP gene. Prion proteins cannot self-replicate and cannot be considered life. However, while prions are composed of misfolded protein aggregates, they propagate by inducing conformational changes in normal prion proteins (PrP^C) to transform them into the abnormal, disease-causing form (PrP^Sc). The misfolded prion acts as a template, guiding the normal proteins to adopt the abnormal structure, exhibiting characteristics of life. This precisely supports the viewpoint of this paper that any self-replicating molecule, including misfolded prions, can serve as genetic material and ultimately become life. Additionally, I have included examples of prions in the revised version of my paper. Viral capsids are part of a virus and are composed of proteins encoded by viral genes. To my knowledge, I have not seen viral capsids self-replicate. If there were independent viral capsids that could self-replicate (no need for DNA or RNA), I would also define them as life. Thank you very much for your suggestion. I have added a clearer definition of life to my paper in the conclusion section and changed the title to " Life should be redefined: Any molecule with the ability to self-replicate should be considered life ". Additionally, it should be emphasized that self-replication should also include one molecule inducing another molecule to become itself (such as a misfolded prions induce prions).

3.   I believe there may be a misunderstanding. According to England's theory, DNA or RNA molecules exist in a high-energy (low entropy, ordered and organized) state, which makes them ordered. The replication of DNA or RNA molecules progresses towards a lower energy state, ultimately leading to a low-energy (higher entropy, disordered and disorganized). This process is driven by the second law of thermodynamics, which governs the behavior of all matter in the universe, including life. However, an increase in entropy driven by the second law of thermodynamics does not necessarily indicate life; only molecules with active self-replication functions are considered life. The second law of thermodynamics drives all matter in the universe towards disorder and heat death. For example, if a drop of ink is added to a cup of water, the ink will eventually distribute evenly among the water molecules due to the second law of thermodynamics, which is unrelated to life, vice versa. I am very grateful for your suggestions on my paper. I have been contemplating new perspectives on life during this period, and I have added new paragraph accordingly.
Authors' point by point response to the Reviewer comments is as follows -

1.   I have considered this issue while writing my paper, but I have been very cautious. I am also concerned that my viewpoint may be too radical and difficult to accept. However, with the help of the F1000Research platform and the opportunity to answer questions, my response is: Yes. Traditional thinking defines life as having certain perceptions or consciousness, such as in humans, animals, and plants. However, the emergence of viruses has challenged this common understanding. A virus is merely a sequence of DNA or RNA, and although it is an organic substance (without consciousness, is it different from inorganic substances?), it constantly replicates and is also a form of life. I believe we can be bolder. In my article, I speculate that inorganic substances capable of self-replication can also be considered life, which is a novel viewpoint in this paper. Regarding the statement 'limestone could be considered to replicate by utilizing marine life,' I disagree because limestone is not self-replicating; its production results from the accumulation of products from marine biological activities. I think it is essential to emphasize self-replication, which involves actively replicating oneself.

2.   This question is very interesting. The main point of the paper is that molecules capable of self-replication can be defined as life, similar to a piece of DNA (virus) that can self-replicate. If a molecule only drives its own self-assembly from simple substrates to more complex biomolecules, I believe this is growth, not replication, and therefore not life. I think the example of prions is also a form of life. Prion protein is coded by the PRNP gene. Prion proteins cannot self-replicate and cannot be considered life. However, while prions are composed of misfolded protein aggregates, they propagate by inducing conformational changes in normal prion proteins (PrP^C) to transform them into the abnormal, disease-causing form (PrP^Sc). The misfolded prion acts as a template, guiding the normal proteins to adopt the abnormal structure, exhibiting characteristics of life. This precisely supports the viewpoint of this paper that any self-replicating molecule, including misfolded prions, can serve as genetic material and ultimately become life. Additionally, I have included examples of prions in the revised version of my paper. Viral capsids are part of a virus and are composed of proteins encoded by viral genes. To my knowledge, I have not seen viral capsids self-replicate. If there were independent viral capsids that could self-replicate (no need for DNA or RNA), I would also define them as life. Thank you very much for your suggestion. I have added a clearer definition of life to my paper in the conclusion section and changed the title to " Life should be redefined: Any molecule with the ability to self-replicate should be considered life ". Additionally, it should be emphasized that self-replication should also include one molecule inducing another molecule to become itself (such as a misfolded prions induce prions).

3.   I believe there may be a misunderstanding. According to England's theory, DNA or RNA molecules exist in a high-energy (low entropy, ordered and organized) state, which makes them ordered. The replication of DNA or RNA molecules progresses towards a lower energy state, ultimately leading to a low-energy (higher entropy, disordered and disorganized). This process is driven by the second law of thermodynamics, which governs the behavior of all matter in the universe, including life. However, an increase in entropy driven by the second law of thermodynamics does not necessarily indicate life; only molecules with active self-replication functions are considered life. The second law of thermodynamics drives all matter in the universe towards disorder and heat death. For example, if a drop of ink is added to a cup of water, the ink will eventually distribute evenly among the water molecules due to the second law of thermodynamics, which is unrelated to life, vice versa. I am very grateful for your suggestions on my paper. I have been contemplating new perspectives on life during this period, and I have added new paragraph accordingly.
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Reviewer Report 21 Aug 2024

Denis Noble, University of Oxford, Oxford, UK

Approved

https://doi.org/10.5256/f1000research.166604.r312177

This Review article proposes that there could be other self-replication molecules in addition to DNA & RNA. It also supports England's (2015) hypothesis that entropic forces are responsible for making matter adopt life-like physical properties. It justifies this speculation using ... Continue reading

Is the topic of the opinion article discussed accurately in the context of the current literature?

Yes
Are all factual statements correct and adequately supported by citations?

Yes
Are arguments sufficiently supported by evidence from the published literature?

Yes
Are the conclusions drawn balanced and justified on the basis of the presented arguments?

Partly

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Cardiac electrophysiology, evolutionary biology.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

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Author Response 17 Sep 2024

Zheng Liu, Guilin Medical University, China

17 Sep 2024

Author Response

Thank you very much for recognizing the viewpoints presented in this paper. The open new mode of F1000Research allows me to express novel viewpoints and share them with other academic ... Continue reading Thank you very much for recognizing the viewpoints presented in this paper. The open new mode of F1000Research allows me to express novel viewpoints and share them with other academic scholar. These viewpoints are often difficult to get accepted by traditional journals, but I believe that the emergence of any novel viewpoint will drive progress in science and thought.
Thank you very much for recognizing the viewpoints presented in this paper. The open new mode of F1000Research allows me to express novel viewpoints and share them with other academic scholar. These viewpoints are often difficult to get accepted by traditional journals, but I believe that the emergence of any novel viewpoint will drive progress in science and thought.
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Author Response 17 Sep 2024

Zheng Liu, Guilin Medical University, China

17 Sep 2024

Author Response

Thank you very much for recognizing the viewpoints presented in this paper. The open new mode of F1000Research allows me to express novel viewpoints and share them with other academic ... Continue reading Thank you very much for recognizing the viewpoints presented in this paper. The open new mode of F1000Research allows me to express novel viewpoints and share them with other academic scholar. These viewpoints are often difficult to get accepted by traditional journals, but I believe that the emergence of any novel viewpoint will drive progress in science and thought.
Thank you very much for recognizing the viewpoints presented in this paper. The open new mode of F1000Research allows me to express novel viewpoints and share them with other academic scholar. These viewpoints are often difficult to get accepted by traditional journals, but I believe that the emergence of any novel viewpoint will drive progress in science and thought.
Competing Interests: The author declares no conflicts of interest. Close
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Version 2

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Denis Noble, University of Oxford, Oxford, UK
Kevin S. Lang, University of Minnesota, Saint Paul, USA

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10 Oct 2024 | for Version 2

Kevin S. Lang, University of Minnesota, Saint Paul, MN, USA

5 Views Cite this report Responses(0)

Approved

I think the author addressed my concerns adequately with their revisions.

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No competing interests were disclosed.

Reviewer Expertise

DNA Replication, transcription, translation, microbiology, molecular biology, evolution.

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23 Aug 2024 | for Version 1

Kevin S. Lang, University of Minnesota, Saint Paul, MN, USA

25 Views Cite this report Responses(1)

Approved With Reservations

The author should consider providing a more explicit suggestion of what they think the definition should be tailored to. For example, is life strictly constrained by the replication of only organic molecules? Could replication of inorganic molecules be considered “life”? This is important as the author highlights that some organic molecules (ie genes) utilize organisms for their own replication. Parallel to this framework, things like limestone could be considered to replicate by utilizing marine life for its replication. Would this then be considered life?
In line with the above comment, would the new definition of life pertain to molecules that template their own replication or self-assembly? The author discusses the generation of biomolecules from inorganic substrates, citing the RNA theory of the origin of life. This is an example of self-assembly. Other examples of this beyond RNA and DNA exist on Earth, for example, prions and viral capsids. The distinction of these molecules is that they don’t necessarily involve templating their own replication. Rather, they drive their own self-assembly from simple substrates to more complex biomolecules. A clearer definition would enhance this essay from being a simple review of existing ideas to proposing a novel definition.
Lastly, the author highlights indexed essays that discuss the relationship between life and entropic forces. However, the way the author discusses the relationship between life and entropy is unclear. For example, the author states that DNA and RNA are in a state of high entropy. This is perplexing, given that these biomolecules are highly ordered, and thus fighting against entropy. Therefore, is the author stating that the new definition of life should be any molecules that are moving to a state of low entropy, and thus, driving themselves away from natural tendency of the 2^nd law of thermodynamics to increase entropy?

In summary, this is an intriguing essay that will benefit by a more explicit definition of what should be considered “life”.

Is the topic of the opinion article discussed accurately in the context of the current literature?

Partly
Are all factual statements correct and adequately supported by citations?

Partly
Are arguments sufficiently supported by evidence from the published literature?

Partly
Are the conclusions drawn balanced and justified on the basis of the presented arguments?

Partly

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

DNA Replication, transcription, translation, microbiology, molecular biology, evolution.

Respond to this report

Responses (1)

Author Response

20 Sep 2024

Zheng Liu, Guilin Medical University, China

Authors' point by point response to the Reviewer comments is as follows -

1.   I have considered this issue while writing my paper, but I have been very cautious. I am also concerned that my viewpoint may be too radical and difficult to accept. However, with the help of the F1000Research platform and the opportunity to answer questions, my response is: Yes. Traditional thinking defines life as having certain perceptions or consciousness, such as in humans, animals, and plants. However, the emergence of viruses has challenged this common understanding. A virus is merely a sequence of DNA or RNA, and although it is an organic substance (without consciousness, is it different from inorganic substances?), it constantly replicates and is also a form of life. I believe we can be bolder. In my article, I speculate that inorganic substances capable of self-replication can also be considered life, which is a novel viewpoint in this paper. Regarding the statement 'limestone could be considered to replicate by utilizing marine life,' I disagree because limestone is not self-replicating; its production results from the accumulation of products from marine biological activities. I think it is essential to emphasize self-replication, which involves actively replicating oneself.

2.   This question is very interesting. The main point of the paper is that molecules capable of self-replication can be defined as life, similar to a piece of DNA (virus) that can self-replicate. If a molecule only drives its own self-assembly from simple substrates to more complex biomolecules, I believe this is growth, not replication, and therefore not life. I think the example of prions is also a form of life. Prion protein is coded by the PRNP gene. Prion proteins cannot self-replicate and cannot be considered life. However, while prions are composed of misfolded protein aggregates, they propagate by inducing conformational changes in normal prion proteins (PrP^C) to transform them into the abnormal, disease-causing form (PrP^Sc). The misfolded prion acts as a template, guiding the normal proteins to adopt the abnormal structure, exhibiting characteristics of life. This precisely supports the viewpoint of this paper that any self-replicating molecule, including misfolded prions, can serve as genetic material and ultimately become life. Additionally, I have included examples of prions in the revised version of my paper. Viral capsids are part of a virus and are composed of proteins encoded by viral genes. To my knowledge, I have not seen viral capsids self-replicate. If there were independent viral capsids that could self-replicate (no need for DNA or RNA), I would also define them as life. Thank you very much for your suggestion. I have added a clearer definition of life to my paper in the conclusion section and changed the title to " Life should be redefined: Any molecule with the ability to self-replicate should be considered life ". Additionally, it should be emphasized that self-replication should also include one molecule inducing another molecule to become itself (such as a misfolded prions induce prions).

3.   I believe there may be a misunderstanding. According to England's theory, DNA or RNA molecules exist in a high-energy (low entropy, ordered and organized) state, which makes them ordered. The replication of DNA or RNA molecules progresses towards a lower energy state, ultimately leading to a low-energy (higher entropy, disordered and disorganized). This process is driven by the second law of thermodynamics, which governs the behavior of all matter in the universe, including life. However, an increase in entropy driven by the second law of thermodynamics does not necessarily indicate life; only molecules with active self-replication functions are considered life. The second law of thermodynamics drives all matter in the universe towards disorder and heat death. For example, if a drop of ink is added to a cup of water, the ink will eventually distribute evenly among the water molecules due to the second law of thermodynamics, which is unrelated to life, vice versa. I am very grateful for your suggestions on my paper. I have been contemplating new perspectives on life during this period, and I have added new paragraph accordingly.

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Competing Interests

No competing interests were disclosed.

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Reviewer Report

24 Views

21 Aug 2024 | for Version 1

Denis Noble, University of Oxford, Oxford, UK

24 Views Cite this report Responses(1)

Approved

Is the topic of the opinion article discussed accurately in the context of the current literature?

Yes
Are all factual statements correct and adequately supported by citations?

Yes
Are arguments sufficiently supported by evidence from the published literature?

Yes
Are the conclusions drawn balanced and justified on the basis of the presented arguments?

Partly

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Cardiac electrophysiology, evolutionary biology.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (1)

Alongside their report, reviewers assign a status to the article:

Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested

Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.

Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions

[1] Araújo VA, Dias LG, Serrão JE: Rapid and efficient mating in mayflies (Ephemeroptera): morphological and reproductive strategies in primitive winged insects. Naturwissenschaften. 2021; 108(2): 10. PubMed Abstract | Publisher Full Text

[2] Arias-Gonzalez JR: Entropy involved in fidelity of DNA replication. PLoS One. 2012; 7: e42272. PubMed Abstract | Publisher Full Text | Free Full Text

[3] Becker S, Thoma I, Deutsch A, et al.: A high-yielding, strictly regioselective prebiotic purine nucleoside formation pathway. Science. 2016; 352(6287): 833–836. PubMed Abstract | Publisher Full Text

[4] Colomer I, Morrow SM, Fletcher SP: A transient self-assembling self-replicator. Nat. Commun. 2018; 9(1): 2239. PubMed Abstract | Publisher Full Text | Free Full Text

[5] Chatterjee S: Defining Life. From Stardust to First Cells. Cham: Springer; 2023. Publisher Full Text

[6] England JL: Statistical physics of self-replication. J. Chem. Phys. 2013; 139(12): 121923. PubMed Abstract | Publisher Full Text

[7] England JL: Dissipative adaptation in driven self-assembly. Nat. Nanotechnol. 2015; 10(11): 919–923. PubMed Abstract | Publisher Full Text

[8] Fleck R: The Laws of Thermodynamics. Entropy and the Second Law of Thermodynamics. Cham: Springer; 2023. Publisher Full Text

[9] Gardner A, Welch JJ: A formal theory of the selfish gene. J. Evol. Biol. 2011; 24: 1801–1813. PubMed Abstract | Publisher Full Text

[10] Higgs PG, Lehman N: The RNA World: molecular cooperation at the origins of life. Nat. Rev. Genet. 2015; 16(1): 7–17. PubMed Abstract | Publisher Full Text

[11] Hudson R, de Graaf R , Strandoo Rodin M, et al.: CO2 reduction driven by a pH gradient. Proc. Natl. Acad. Sci. USA. 2020; 117(37): 22873–22879. PubMed Abstract | Publisher Full Text | Free Full Text

[12] Klunk J, Vilgalys TP, Demeure CE, et al.: Evolution of immune genes is associated with the Black Death. Nature. 2022; 611: 312–319. PubMed Abstract | Publisher Full Text | Free Full Text

[13] Kosikova T, Hassan NI, Cordes DB, et al.: Orthogonal Recognition Processes Drive the Assembly and Replication of a [2]Rotaxane. J. Am. Chem. Soc. 2015; 137(51): 16074–16083. PubMed Abstract | Publisher Full Text

[14] Markov PV, Ghafari M, Beer M, et al.: The evolution of SARS-CoV-2. Nat. Rev. Microbiol. 2023; 21: 361–379. Publisher Full Text

[15] Noble D, Noble R: Origins and demise of selfish gene theory. Theor Biol Forum. 2022; 115(1-2): 29–43. PubMed Abstract | Publisher Full Text

[16] Samanta B, Joyce GF: A reverse transcriptase ribozyme. elife. 2017; 6: e31153. PubMed Abstract | Publisher Full Text | Free Full Text

[17] Schulze-Makuch D, Irwin LN: The prospect of alien life in exotic forms on other worlds. Naturwissenschaften. 2006; 93(4): 155–172. PubMed Abstract | Publisher Full Text

[18] Welsch F, Kervio E, Tremmel P, et al.: Prolinyl Nucleotides Drive Enzyme-Free Genetic Copying of RNA. Angew. Chem. Int. Ed. Engl. 2023; 62(41): e202307591. PubMed Abstract | Publisher Full Text

Life should be redefined

Abstract

Keywords

Introduction

The expectation for reproduction of organisms

Selfish genes drive reproduction

Figure 1. Entropic forces drive the evolution, leading to the generation of new life forms.

Life begins with RNA

Entropic forces drive life

RNA and DNA are not the only genetic materials

Any molecules with self-replicating ability can be genetic material

Conclusions

Ethical approval and consent

Data availability

References

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