Unravelling the Origin of Life

Ever wondered how life appeared on Earth — the only planet known so far to harbour life — and gave rise to all the complex and beautiful forms of life we see today?

We have learned a lot about how life has diversified and developed over millions of years since its inception. But despite decades of work in this domain, a clear understanding of how inanimate molecules first transformed into functional living systems evades us even today!

Before thinking about how life originated on earth, it is prudent to reflect on two questions: How exactly do we define life? And what are the necessary and sufficient conditions to call something living?

Dabbling to define life

Life in all its complexity originated out of non-living matter. For this to occur, multiple components came together and their interactions produced the phenomenon of life.

Although we only know about the emergence of carbon-based systems of life on Earth, we cannot preclude the possibility of other systems of life (such as Silicon, Selenium, Nitrogen, Phosphorus-based systems). While scientists are still looking for evidence of such alternative systems on other planets, for this article, we will restrict ourselves to exploring the origins of life as we know it.

Scientists and philosophers have been constantly trying to come up with more precise and encompassing definitions of life. A widely recognized definition developed by NASA describes life as “any self-sustaining chemical system capable of Darwinian evolution”. According to a popular textbook by Douglas Futuyma, evolution is defined as the “change in the properties of groups of organisms over the course of generations”.

Such a chemical system should ideally exhibit some key features of Darwinian evolution:

1. Heredity: being able to pass on genetic information (instructions that specify how individuals  carry out essential living functions) to its offsprings
2. Variation: being able to generate random differences in these genetic instructions
3. Selection: being able to use these pre-existing genetic differences in its population to adapt to the environment and thereby allow better-adapted individuals to eventually reproduce further

Having a functional definition of living systems then enables scientists to ask many more specific questions pertaining to the origin of life:

1. How did various geochemical and physicochemical conditions on the early Earth influence the formation of complex biomolecules from the simpler chemical compounds?
2. How does Darwinian evolution occur in such a prebiotic chemical system?
3. How did the genetic code of life arise?

For this article, we will be exploring the first question in depth. Doing so requires us to travel back to about 4 billion years ago to understand early Earth’s geological, chemical and physical environment and the conditions that made it possible for life to emerge in the first place.

Examining early Earth conditions

When the Earth was first formed about 4.5 billion years ago, it was a naked planet devoid of any oceans or an atmosphere. Constant showers of asteroids are believed to be the original source of aqueous material on early earth. But, all of this water existed in the form of water vapour given the extremely hot temperature of the early Earth. 

Around 3.9 billion years, as the Earth began cooling down, the surrounding water vapour gradually condensed to form the oceans. Further, plate tectonic motions at that time led to frequent volcanic eruptions across the planet, which released volcanic rocks, water vapour, and gases like carbon dioxide, nitrogen, methane, sulphur dioxide, into the atmosphere.

Miller-Urey’s landmark spark-discharge experiment in 1953 suggested that the specific milieu of chemical, physical and geological conditions of the early Earth could provide an environment for the spontaneous generation of complex biomolecules like amino acids.

Scientists believe that biomolecules produced in the early earth could have self-assembled and developed several new features due to interactions between them (this phenomenon is called emergence). Examples of such emergent features include the ability to form closed compartments (such as vesicles) and the ability to replicate such compartments by dividing into two smaller compartments (replication). 

Vesicular compartments are formed by the aggregation of amphiphiles — entities made up of water-loving molecules on one side and lipid-loving molecules on the other that results in the formation of closed compartments. This separates a vesicle’s internal environment from its outside environment and makes the regulation of its internal environment possible. Vesicles are believed to be the precursors of cellular compartments, which are primarily made up of amphiphiles called phospholipids.

But what do we know about the earliest known evidence of life on earth and when did it emerge? Let us look at some historical sources of evidence to develop a tentative timeline for the origin of life.

Constructing a timeline for the origin of life

Genetic studies in the last few decades have suggested that present-day life forms originated from an entity called the Last Universal Common Ancestor (or LUCA), which is believed to have existed around 2.5 billion years ago. 

Despite the advent of modern gene sequencing technologies, scientists have still not arrived at a precise genetic sequence for LUCA due to the challenges of reconstructing historical sources of evidence. 

But why is LUCA so critical to deciphering the origin of life? Although it may not conclusively solve the origin of life question, LUCA can potentially provide important insights into the timeline of the emergence of complex living systems and help us understand the key differences between early living systems and present ones. 

In addition to LUCA, scientists have also been studying geological evidence in order to arrive at a precise timeline of the origin of life. They regularly unearth numerous fossils and geological artefacts to search for traces of the earliest life forms and deduce the geological composition of the early earth. Stromatolites are one such routinely studied fossils that are mat-like sedimentary structures formed by colonies of microorganisms compressed into stone. Carbon dating of Stromatolite fossils show they are approximately 3.5 billion years old, and this helps narrow down the era in which life could have originated on Earth. Given that our planet became habitable around 4 billion years ago, and Stromatolites emerged around 3.5 billion years ago, the origin of life must have occurred within the band of about 500 million years!

While the precise time for the origin of life still remains tentative, there has been significant progress in the last few decades in terms of better understanding the mechanism for the origin of life on Earth.

Deciphering the mechanisms of origin of life

There are two predominant approaches or schools of thought among scientists for explaining how life may have first emerged and what it might have looked like.

Metabolism-first hypothesis:

The metabolism-first hypothesis proposes that early Earth was abundant with simple chemicals that could have produced biomolecules needed for life through a series of catalytic reactions. One of the earliest theories supporting this hypothesis is the coacervate theory that was first proposed by the Russian biochemist, Alexander I. Oparin in 1924. 

The coacervate theory proposes that iron carbides react with water vapour to form hydrocarbons, which upon oxidation can form compounds like alcohols, aldehydes and other chemicals. These compounds can further react with ammonia to form amines, amides and other ammonia products, which can function as protein precursors and aggregate to form small colloidal droplets called coacervates. These coacervates are distinct liquid phases within aqueous media, and can help encapsulate essential biomolecules and functionalities into closed compartments, thus forming a very primitive form of a cell - the building block of life!

A British scientist, JBS Haldane also independently proposed a similar idea through his primordial soup theory in 1929, which describes how life could have originated within the hot and dilute soup-like oceans of the early Earth. 

Inspired by Oparin and Haldane’s theory, Stanley Miller and Harold Urey experimentally demonstrated in 1953 that biomolecules such as amino acids could be synthesised in a simple spark discharge experiment under a reducing environment. Their experiment involved sealing a mixture of water, methane, hydrogen and ammonia in a glass flask and subjecting it to heat and continuous electrical sparks. 

These experimental conditions mimicked the early Earth’s chemical and physical environment in terms of the atmospheric composition and frequent lightning discharges. It is important to note that oxygen wasn’t yet part of the earth’s atmosphere during that time, thereby necessitating the use of an overall reducing environment in this experiment. 

Using paper chromatography to analyse the experimental products, Miller and Urey found traces of five amino acids: glycine, α-alanine, β-alanine, aspartic acid and α-aminobutyric acid. Further experiments with the addition of gases such as carbon dioxide and nitrogen (to better align with the latest geological findings about the Earth’s composition 4 billion years ago), produced even more diverse organic compounds such as iso-serine and α-amino adipic acid.

While Oparin and Haldane’s theories were critical to the development of the field of ‘origin of life’ research, they could not be experimentally validated. Even after Urey and Miller’s attempts at producing complex biomolecules and the consequent excitement this experiment caused about solving the origin of life problem, the gap between producing complex biomolecules and creating the first functional living organism in the laboratory still remained to be filled.

Around the same time in 1954, Krishna Bahadur, an Indian chemist reported the formation of microscopic colloidal structures called Jeewanu (Sanskrit for a “unit of life”) using simple chemical precursors. Bahadur used a sterilised cocktail of organic and inorganic compounds (such as formaldehyde, citric acid, ammonium phosphate, calcium acetate, potassium sulfate) and exposed them to sunlight for a few days. Upon observing these exposed cocktail samples under the microscope, he saw several spherical budding structures (Jeewanu) that were later shown to contain biomolecules such as amino acids, sugars, and nucleobases.

A few decades later in the 1980s, Gunter Wachtershauser proposed the theory of surface metabolism, which further substantiated the metabolism-first hypothesis. Wachtershauser proposed that the first forms of life were autotrophic (organisms that produce their own food) and used carbon fixation (and therefore called chemoautotrophs). He argued that these membrane-less entities were confined to electrically-charged iron sulphide mineral surfaces (such as pyrite) and could replicate without any defined cell division mechanisms. Wachtershauser’s theory eventually led to more extensive studies of the origin of life within hydrothermal vents.

Despite multiple groundbreaking theories supporting the metabolism-first hypothesis, several aspects of how genetic information was stored and transmitted in living systems remained unanswered. In order to address these gaps in our understanding, the gene-first hypothesis also started gaining prominence.

Genes-first hypothesis:

The gene-first hypothesis proposes that an information-storage mechanism (such as DNA and RNA) preceded the emergence of metabolism for the origin of life on Earth. As part of this hypothesis, Alexander Graham Cairns-Smith proposed the Cairn-Smith’s model of clay life in the mid-1960s. This model stated that clay minerals could have served as an initial hereditary material that could replicate itself via crystallization. Such clay-based living systems could have the ability to fix carbon and nitrogen, harness sunlight, and also synthesize biomolecules. The model hypothesized that during the later stages of development and evolution, these clay-based living systems could have used organic molecules in the environment to produce genes. Although this theory gained some attention initially, it largely remains disputed in the scientific community due to a lack of plausible experimental evidence.

A much more actively-researched hypothesis currently backing up the gene-first approach is the RNA world hypothesis. The term ‘RNA world’ was first coined by Walter Gilbert, but the idea has existed since 1968 in the publications of Francis Crick and Leslie Orgel. This hypothesis proposes that RNA came about before the emergence of proteins and DNA, and potentially served the dual functions of catalysis and information storage. These functions are respectively fulfilled by proteins and DNA in most living systems existing today. Over the years, many more pieces of evidence backing the RNA world hypothesis have also emerged. 

For instance, the discovery of RNA-based enzymes called ribozymes in the 1980s showed that RNA can serve as catalysts for various biochemical processes such as splicing of DNA and biosynthesis of transfer RNAs (tRNAs). RNA has also been shown to be self-reproducing and has for long been a candidate for the first information-storage biomolecules capable of replication.

Scientists have also, to some extent, been able to artificially select replicating variants of RNA in the lab to produce RNA replicase - RNA-based enzymes responsible for copying the genetic sequences of other RNA molecules. Furthermore, RNA molecules could have an even deeper role in the emergence of living systems, given the recent discovery of small non-coding RNA which can act as genetic regulatory elements in the cell. 

But, the larger question of how RNA molecules first emerged on early Earth still remains unanswered. Since the spontaneous emergence of RNA is highly implausible, given its high energy requirements, the RNA world hypothesis still remains to be fully accepted. RNA is also known to be chemically unstable over extended periods of time and would be highly susceptible to hydrolysis and degradation under prebiotic conditions.

In the light of these limitations to the RNA world hypothesis, scientists have proposed several other potential candidates for information-storing biomolecules, such as genetic polymers made up of other hybrid building blocks such as peptide nucleic acids (PNAs), threose nucleic acids (TNAs), and glycerol nucleic acids (GNAs).

Looking ahead

While all these approaches and schools of thought have progressively improved our understanding of the origin of life, its mechanisms and its spawning conditions, they have also exposed several deficiencies and gaps in our current understanding. To address these concerns, scientists are now trying to work on hybrid models combining the gene-first and metabolism-first hypotheses.

One such hybrid and interdisciplinary approach focuses on autocatalytic systems. Autocatalytic systems are collections of molecules and chemical reactions capable of information storage as well as catalysing their own replication. These properties allow them to be closed and self-sustaining systems.

In 1971, Stuart Kauffman, Manfred Eigen, Otto Rössler were the first to independently apply the concept of autocatalytic systems to the origin of life problem. In particular, Kauffman also used computational simulations and modelling-based approaches to study the likelihood of the emergence of autocatalytic sets of protein in prebiotic conditions. While there have been several many theoretical studies of autocatalytic systems over the years, experimental studies focussing on the roles and implications of Kauffman’s model have only gained prominence in the last few decades.

A collaborative group of scientists at the NCBS Bangalore, University of Delhi and ESPCI Paris have been collectively studying RNA-based autocatalytic systems to help further our understanding of the mechanisms of origin of life. 

To know more about their work and understand how autocatalytic systems can contribute to our understanding of the origin of life problem, tune in to the next article of our two-part series on Unravelling the Origin of Life. We will dive deep into research on autocatalytic systems, and explore the need for interdisciplinary approaches for understanding the origin of life on Earth. Stay tuned!