Book Review: "Systems Approach To Astrobiology" By Benton C. Clark & Vera M. Kolb

 

    I have just finished reading this wonderful book on astrobiology. It's not a long read, but some of the language is a little technical and it requires at least some background and understanding of general biochemistry terminology. But overall, if you're looking for a clear introductory book for learning more about astrobiology, I would highly recommend Systems Approach To Astrobiology.

    The first chapter goes through general understanding of what astrobiology is, including what it aims to achieve and what type of scientific field it is. Chapter one also goes through what a system is, and its composition and characteristics. What this book does well is emphasizing the importance of systems analysis and analyzing data through the context of an entire system rather than in isolation. This is very crucial in astrobiology and systems chemistry, because so many subsets and subsystems depend on each other and are highly affected by each other.

    Chapter 4 goes into depth on analyzing the different definitions of a living system and when a system can count as living. This can of course become very unclear as there are many complex steps in the transition from abiotic chemistry to the first protocell. The chapter also goes into the uniqueness of living systems, subsystems of metabolism, ATP, alternative primordial energy currencies other than ATP, and more.     

    Chapters 5 & 6 are about systems chemistry and prebiotic chemistry.  Chapter 5 covers molecular networks, self-replicators, and emerging features as prebiotic evolutionary transitions. Chapter 6 discusses prebiotic chemical feasibility, molecules found in space from meteorites and other sources, differences between modern enzymes and prebiotic reactions, and also goes through some learning phases experienced by origin of life researchers throughout the years and where the field is now. Chapters 7-10 go through all of this through a systems standpoint, and weigh these prebiotic chemistry problems against other factors within a gigantic system with different feedback loops, intricate chemical complexity, etc.

    Chapter 11 is focused on panspermia and the interplanetary transport of life. Chapter 12 is a general overview of systems analysis. 

    I just finished the book today and recommend it to all of you interested in planetary science, astrobiology, origin of life, molecular evolution, etc. Enjoy! 

    

    

In An RNA World: Why RNA Or An RNA-Like Nucleic Acid Is Such A Popular Candidate For The Origin Of Life

 

A Divided Puzzle

The origin of life remains a puzzle, and may always be that way in the sense that we won't ever completely understand the exact chemistry that gave rise to the first protocell. But the main reason as to why this is the case is the fact that there are many plausible scenarios in which it could have occurred. Never mind the complex chemistry that gave rise to the first building blocks - there is still much division as to what these first building blocks even were. Besides the RNA world, we have metabolism-first, panspermia, iron-sulfur world, clay hypothesis, and more. However, the RNA world remains to be the most plausible explanation for abiogenesis for many scientists. 

The Uniqueness Of RNA 

There are certain features and capabilities of RNA that render it unique and favorable in terms of prebiotic chemistry. For one, it somewhat solves the chicken-and-the-egg paradox in the sense that it functions as a genetic molecule that also catalyzes its own replication. And this replication in turn serves as somewhat of a kickstarter to Darwinian evolution in a molecular genetic sense (opposed to purely chemical systems preceding its emergence). Selection based on the efficiency of RNA replication in which those that display improved replication are selected for seems plausible in and of itself. but another chicken-and-the-egg paradox arises. Some form of evolution is required for the first primitive self-replicating ribozyme to emerge, but without the self-replication feature, there can't be an evolutionary search.  One theory that's been suggested as to the origins of RNA evolution without the assistance of an evolved catalyst is template-directed synthesis, in which some copying occurs preceding the first replicase ribozyme. Basically, RNA can drive chemical reactions as well as store genetic information, making proteins and DNA unnecessary in this origin of life scenario. 

Pre-RNA

While RNA seems like a good candidate for the first self-replicating molecule, it's probably not the very first one. There are a few reasons for this:

(1) It's hard to form long RNA molecules without enzymes.

(2) The building blocks of RNA (ribonucleotides) are difficult to create naturally.

(3) Forming RNA requires a specific type of chemical bond (3' to 5' phosphodiester) to happen repeatedly, but many other reactions could interfere.

Because of these challenges, scientists think the first self-replicating molecules might have been simpler polymers that were similar to RNA. We don't have any traces of these molecules today, but their simpler structure makes them more likely candidates for the first information-storing and catalytic molecules on Earth.

The transition to an RNA world might have happened when these simpler molecules acted as templates and catalysts to create RNA. Lab experiments show that one such simpler molecule (PNA) can indeed act as a template for making RNA.

These pre-RNA molecules likely also helped form the building blocks of RNA from even simpler chemicals. Once RNA appeared, it could have gradually taken over the functions of the pre-RNA molecules, leading to the RNA world.

Emergence Of RNA On The Early Earth 

RNA emerged from nucleotides, likely in warm, shallow ponds on the early Earth. Organic (carbon-based) compounds would have leeched in through drainage and precipitation. Nucleotides likely formed from simpler precursor molecules in this mish mash of organic compounds, aided by wet-dry cycling as well as UV radiation as an energy source. 

The first cells with membranes likely formed when certain molecules that can interact with both water and fats (amphipathic molecules) spontaneously came together to create a barrier. This barrier enclosed a mixture of self-replicating RNA (or its precursor) and other molecules. We're not sure exactly when in the evolution of biological catalysts this happened.

Once RNA molecules were enclosed within these membranes, they could evolve more effectively as carriers of genetic information. This enclosure allowed for selection based on two factors:

(1) The structure of the RNA itself.

(2) How the RNA affected other molecules within the same enclosed space.

This meant that the sequence of nucleotides in the RNA could now influence the characteristics of what we'd consider a basic living cell. The membrane created a distinct unit, separating the internal environment from the external world, which is a fundamental feature of life as we know it.

References:

The Origins of the RNA World

The RNA World and the Origins of Life

Building Artificial Life: An Introductory Overview Of Synthetic Biology

 

What Is Synthetic Biology? 

While origin of life research generally pertains to figuring out the pathways of chemical systems that produced the earliest protocells (in a geochemically plausible scenario), there is a different yet overlapping field that is constantly approaching new frontiers - Synthetic Biology. Synthetic biology is directly concerned with building artificial life, whether it be in the form of protocells/cells, organisms with expanded or reduced genetic codes, synthetic DNA and genomes, hybrid biological systems, artificial organelles, and more. 

Synthetic biology relies upon multiple scientific fields in order to expand its horizons, including but not limited to - bioengineering, biotechnology, molecular biology, genetics, nanotechnology, systems biology, chemical biology, and more. Although synthetic biology has seemingly limitless potential world-changing capabilities, from gaming to medicine, I am most interested in it's ability to build artificial protocells in order to further understand the origin of life. That is what this blog post will focus on.

Synthetic biologists can be categorized into two main groups. One group uses unnatural molecules to mimic emergent behaviors from natural biology, aiming to create artificial life. The other group seeks to use interchangeable parts from natural biology to construct systems that function in novel ways. In both approaches, pursuing synthetic goals compels scientists to explore uncharted territories, addressing problems that are not easily encountered through traditional analysis. This exploration leads to the development of new paradigms that analysis alone cannot readily achieve.

Building Artificial Life

In 2010, leading genomic scientist Craig Venter and his research team essentially constructed a synthetic copy of a bacterium's DNA that, once transplanted into an organism, took control of its functions. Obviously, this is different than creating a complete living synthetic organism, but nevertheless, it was a massive leap for the field of synthetic biology. 

Cells are not only the building blocks of biological complexity; they are complex systems maintained by the coordinated interaction of multiple biochemical networks. Their replication, adaptation, and computational abilities arise from appropriate molecular feedback mechanisms. As recent decades have showcased the transition from the description-driven biology to the synthesis-driven biology, it has presented a common challenge to the fields of bioengineering and the origin of life - what are the proper conditions that lead to the emergence and persistence of living cellular structures? 

A hypothesis-driven approach to biology has enabled the control and design of new cellular functions and genetic circuits. Two main approaches have been considered towards protocell synthesis. The first one is a top-down approach and involves the construction of a minimal cell by reducing the genome of existing cells. The other main approach, bottom-up, involves starting from scratch: from scratch: a life-like entity is constructed via self-assembling molecular components, whether biological in nature or completely ad hoc chemical components. 

Although self-replication and evolution are important abilities of cells, they do not necessarily need to be end goals of protocells constructed via synthetic biology. The artificial cell (Acell) could replicate but not evolve, or even be completely unable to self-replicate. Either way, a simple self-sustaining Acell could persist under specific conditions, exchanging energy and matter with its surroundings without growing. Although this might seem like a limited scenario, it is quite intriguing: one could design or guide the self-assembly of a protocell capable of performing certain functions or computations in predefined ways.

This article is meant as a general overview of synthetic biology. I will delve deeper into the actual methods that scientists employ in protocell construction in future blog posts. 

References: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788358/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442389/

https://ntrs.nasa.gov/api/citations/20020043286/downloads/20020043286.pdf

The Genomic Imprint of Evolution

 

Over a century ago, scientists relied on physical and anatomical evidence for the reconstruction of the evolutionary past, namely in the form of transitional fossils in geology/paleontology and vestigial structures in anatomy. It wasn't until the late 1960's and early 1970's that biologist Allan Wilson and colleagues utilized protein electrophoresis to analyze genetic variation among different populations, which led to a better understanding of human origins, including the "Out of Africa" hypothesis, which suggests that modern humans originated in Africa. This continues to be the consensus among scientists today.

Whole Genome Sequencing (WGS)

Whole Genome Sequencing (WGS) is a technique utilized in order to obtain complete DNA sequence of an organism's genome. In order for this to be done, all the genetic material of said organism must be analyzed, including both coding and non-coding regions. The first step of WGS involves collection some form of DNA from an organism, which could be blood, tissue, or other kind of sample. Genomic DNA is then isolated from the sample using DNA extraction methods. Following preparation, the DNA fragments undergo sequencing using high-throughput platforms such as Illumina, PacBio, or Oxford Nanopore. These platforms employ diverse sequencing technologies and methodologies, and generally involve decoding the sequence of nucleotides (A, T, C, and G) within each DNA fragment. Upon completion of sequencing, raw sequence data undergoes analysis through bioinformatics tools and algorithms. This process encompasses quality assessment, aligning sequence reads with a reference genome (if available), detecting genetic variations like single nucleotide polymorphisms (SNPs) and structural variants, and annotating genomic attributes.

Genome Sequencing: Evolutionary Relationships & Evolutionary Past 

Once a genome of a species is sequenced, it can be compared with the genome of another, which aids in the construction of phylogenetic trees which show how the two (or more) species are related to one another, including tracing evolutionary splits. The sequences can also uncover genetic changes throughout lineages, such as crucial mutations, gene duplications, and gene losses; all important processes that helped shape the current genome. Genomic data in addition to fossils found in a certain region can help reveal and pinpoint adaptations that assisted in an organisms survival in that specific period and environment. Instances of horizontal gene transfer, in which genetic material is exchanged between species, can also be detected. Analyzing the genetic diversity within a population of a species can illuminate the dynamics of its evolution, encompassing phenomena like genetic drift, natural selection, and gene flow. This knowledge plays a pivotal role in comprehending the evolutionary trajectories of populations across successive generations.

Genomic Fossils

Genomic fossils are remnants of ancient genetic material or sequences that have been preserved within the genomes of modern organisms. Transposable elements (TEs), also called jumping genes, represent a category of genomic fossils. These DNA sequences possess the ability to relocate or "jump" within a genome, occasionally integrating into fresh positions. As time elapses, certain TEs lose functionality, resulting in preserved "fossilized" duplicates within the genome. Investigation of these vestiges unveils the varieties of TEs that were operative in progenitor species, shedding light on their influence on genome organization and operation. Pseudogenes are gene duplicates that have accumulated mutations, causing them to lose their original functionality. These sequences act as genomic relics, mirroring the evolutionary journey of genes and gene families. Through cross-species comparison of pseudogenes, scientists can deduce instances of gene loss, duplication events, and alterations in function that have transpired throughout evolutionary processes. Occasionally, alleles or genetic variations that were previously beneficial can persist as "fossilized" remnants in the genome despite losing their selective advantage. These (known as ancient alleles) offer insights into past adaptations, selective pressures, and evolutionary shifts prompted by changes in the environment. Also, Certain non-coding DNA sequences, such as regulatory elements or sequences involved in genome organization, can be highly conserved across species. 

References:

Darwinian genomics and diversity in the tree of life

Worlds Beyond: The Search For Other Life In The Cosmos

 

Astrobiology, Geobiology, and Life Beyond 

The field of Astrobiology is concerned with finding biology on other planets or other solid bodies in space.  Geobiology is the study of the interactions between living organisms and their geological environment. It explores how life influences geological processes and how geological factors, such as minerals and rocks, shape and affect life forms. The two fields of course overlap in many ways, as emergence of life throughout the cosmos is greatly dependent on geochemical conditions.  Besides a solid surface with minerals, whether in the form of a rocky planet, dwarf planet, or meteorite, other predictors of life are gaseous atmospheres and water. Chemical reactions are the kick starter for chemistry to turn into biochemistry. These reactions could come about through meteor impacts, volcanic activity, solar rays, hydrothermal vents, and more (or a combination of things). We know that one or a combination of these things led to life emerging on our wet rocky planet of Earth, but how can we detect life on solid surfaces that are beyond our reach? Read on. 

The Pool Of Possibility 

What pool do we have to work with in terms of our options we have to work with? In an (observable) universe that may contain 100 billion to 200 billion galaxies, tens of billions to hundreds of billions of solar systems in each galaxy, and about 10^22 planets, the possibilities may seem endless, but when we go back to the requirements, we need to be more cautious and specific in what we're looking for.  For examples, many planets in the universe are (like Neptune and Saturn in our solar system) gaseous, and therefore highly unlikely to contain life. Other planets may be solid and rocky, but lack the other necessary components such as water and gaseous atmospheres. We can even get more detailed than that, and say that some wet rocky planets may have all the necessary ingredients except carbon, which is crucial for life on Earth because of its unique ability to form complex molecules through chemical bonding. Is non carbon-based life a possibility? Yes, but there's a lot of extraterrestrial chemistry that we know nothing about that would have to be studied in order to even begin to find out. The point is, the problem complexifies with the more (necessary) questions that we ask, and since astrobiology is a multidisciplinary field that incorporates astronomy, biology, chemistry, geology, physics, and more, we need to examine these problems through a systems-approach instead of a singular approach, meaning that we need to tackle each problem within the context of other factors instead of on its own. 

Life Detection Methods

In order to improve and expand our search for extraterrestrial life, we need to employ the most high-quality and cutting edge technology. Spectroscopy as a generalized technique in science is a scientific method of studying objects and materials based on color.  As applied to astrobiology, it's a technique that entails examining the light released or captured by a planet's atmosphere or surface. Researchers search for distinctive patterns, like indications of water, organic compounds, or gases such as oxygen and methane, which might indicate potential biological processes. Chromatography in astrobiology is achieved through simulation experiments and analyses conducted in laboratories using Earth-based analogs or synthetic environments designed to mimic extraterrestrial conditions.  Types of chromatography include gas, liquid, and ion. Gas chromatography is extensively used in astrobiology for analyzing volatile and semi-volatile organic compounds in samples related to extraterrestrial environments or analogs. Liquid chromatography is used in order to separate non-volatile and polar compounds, including biomolecules. Ion chromatography is employed to analyze ionic compounds, including inorganic ions and organic acids. Of course, direct imaging through telescopes is also employed,

but is subject to challenges because stars emit significantly brighter light than the faint reflections from planets. Methods such as coronagraphs, starshades, and interferometry are employed to obstruct or reduce starlight, thereby enhancing the detectability of exoplanets. Capturing images of distant exoplanets in our galaxy or neighboring galaxies necessitates the use of high-powered telescopes equipped with sophisticated adaptive optics technology in order to minimize atmospheric distortions.  Advanced telescopes like the Hubble Space Telescope (HST), the James Webb Space Telescope (JWST), and future space observatories are capable of high-resolution imaging. They can capture detailed images of planetary surfaces, including features like mountains, craters, valleys, and atmospheres.  Space probes and rovers have delivered detailed images of planets and moons within our solar system, revealing their geological characteristics and surface environments. Hopefully sooner than later, advancements in aerospace engineering and long distance space travel can put more rovers, probes, and astronauts deeper into space. We have already observed nucleobase formation in various meteorites, showing that spontaneous formation of genetic building blocks happens elsewhere.

Life Beyond Us: Conclusion 

Some scientists, like biochemist and molecular biologist Dr. Steven Benner think that microscopic microbial life is common on wet rocky planets. Dr. Benner has said that he thinks about 90% of wet rocky planets will have microbial life on them. Other scientists who work (in some way) in astrobiology are less optimistic in terms of the figures they cite. In terms of intelligent life, it largely depends on evolutionary biology and processes in evolution that would produce an intelligent organism. The fascinating endeavor of space exploration and life detection will be an evolving puzzle throughout the 21st century and beyond, and you can contribute to it by pursuing research in one of the many relevant scientific fields that make up astrobiology. 

References:

Astrobiology At NASA - Life Detection

Search for Life outside the Solar System

Life: What It Is And How It Forms

 

Biology emerged from biochemistry which emerged from chemistry which emerged from physics. Sounds simple, no? Not quite. How the first protocell emerged on the early Earth to give way to humans, reptiles, insects, and all other forms of life is a complex and interesting problem that requires various areas of science, from astrobiology to biochemistry to physics in order to answer. But did life actually predate this protocell? According to NASA, life is a "self-sustaining chemical system capable of Darwinian evolution." Let's learn more about such systems. 

Origin Of Life 

It was once thought that chemical systems were disorganized and random. As chemistry and biochemistry in particular advanced, we realized that chemical and molecular systems exhibit features of Darwinian selection. Some molecules gravitate toward self-assembly and eventually form membrane-like structures or other biologically important constructs. Selection predated biology. The subfield of Chemistry that studies selection on a chemical and molecular level is called Systems Chemistry. This subfield is essential for studying the origin of life on Earth and other planets because it can help us discover how these systems generated the first protocell on Earth about 3.8 billion years ago, which then evolved and complexified. 

Dr. Gerald Joyce, a prominent figure in the origin of life research, conducted an experiment that made significant strides in elucidating chemical evolution. The experiment centered on the in vitro evolution of RNA enzymes, also termed ribozymes, which have the capacity to catalyze RNA replication.

Joyce and his research team commenced with a diverse pool of random RNA sequences. They subjected these sequences to a process known as in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). During SELEX, RNA molecules demonstrating even rudimentary abilities to catalyze self-replication were preferentially amplified and isolated. Subsequent rounds of mutation and selection were applied to these chosen molecules, progressively enhancing RNA replicase activity over time. By showing that RNA molecules could evolve in the laboratory to perform a function as complex as self-replication, Joyce provided experimental evidence for the plausibility of chemical evolution. 

Along with this (and other) experimental support, the RNA world hypothesis for the origin of life on Earth is most prominent compared to others (such as metabolism first and protein first) because RNA uniquely contains catalytic as well as informational functions. It is able to catalyze a variety of biochemical interactions as well as store genetic information.

Geochemistry On The Early Earth 

In order to begin understanding the complex process by which this occurred, we must understand the geochemistry. The early Earth was very different than our current beautiful planet. Billions of years ago, Earth had very low levels of oxygen (less than one part per billion) while having carbon dioxide levels likely exceeding 70%. 

In order to replicate conditions on the early Earth and hopefully generate genetic material, Stanley Miller and Harold Urey conducted an experiment simulating early Earth conditions to demonstrate the synthesis of organic compounds from inorganic constituents. They used methane (CH4), ammonia (NH3), hydrogen (H2), and water (H2O) in a ratio of 2:2:1, along with an electric arc to simulate lightning. They were able to produce simple organic compounds, including amino acids, which are the building blocks of proteins and other macromolecules. Although this experiment was an exciting leap for the study of the origin of life, it wasn't without it's inaccuracies. Later research suggests that the Earth's early atmosphere likely consisted of about 97% carbon dioxide (CO2) and 3% nitrogen (N).  In addition, the type of glassware they used, borosilicate glass, was crucial in catalyzing organic compound synthesis. This may not be a major issue, because the first protocell on Earth was generated through mineral and geochemical interactions. 

The most likely settings for where life got started on Earth are hydrothermal vents, tidal pools, and hot springs. There are multiple reasons for this, including them being a rich source of chemical energy, serving as mineral catalysts, and being able to concentrate a high volume of organic (carbon-based) molecules. Another theory is Panspermia, which posits that life emerged on Earth through extraterrestrial delivery (through a meteorite or similar object). Panspermia was more popular among origin of life scientists in years past, but seems to have gone down in popularity, probably because many settings on early Earth were seemingly great for abiogenesis (formation of life from inorganic material) to occur. 

References:

The antiquity of RNA-based evolution | Nature

RNA-catalyzed evolution of catalytic RNA - PubMed (nih.gov)

Geochemistry and the Origin of Life: From Extraterrestrial Processes, Chemical Evolution on Earth, Fossilized Life’s Records, to Natures of the Extant Life - PMC (nih.gov)