Two key classes of chemicals have been seen to operate in all known living things on Earth: amino acids and nucleic acids.  Amino acids are the fundamental building blocks of proteins, which are essential for most biological processes.  Nucleic acids make up the genetic code of all living things on Earth, providing the molecular basis for evolution. Once life formed on Earth, over time it became more complex…eventually leading to humans capable of pondering their own existence. All life on Earth descends from the very first instance of life. Natural selection drove species to form and adapt to new environments and ecological niches. The rise of oxygen in the atmosphere about 2.5 billion years ago caused a proliferation of new life forms that had more efficient metabolic pathways. We will look at some of the milestones in the formation of more complex life throughout Earth’s 4.5 billion year history.

Amino Acids to Proteins

Amino acids and the proteins they combine to form are found in every living organism on Earth. Proteins are needed to make critical biological reactions happen on timescales relevant to life. Proteins regulate the processes that drive life. Though proteins are found across all living things and carry out a wide variety of roles, every protein on Earth is made up of only twenty different amino acids.

Amino Acids

Amino acids are molecules that are defined by a specific structure; all amino acids consist of a central carbon atom forming four bonds to: (1) a hydrogen atom, (2) an amino group (-NH₂), (3) a carboxyl group (-COOH), and (4) a changeable side chain (see Figure 1 below). In organic chemistry, molecules with a carboxyl group are called carboxylic acids. This along with the amino group gives these compounds the name amino acid.

The amino and carboxyl groups allow amino acids to bond to one another through a process of dehydration, i.e. a process that releases water (H₂O).  Figure 2 below diagrams the reaction with structural formulas.  Water is formed by the loss of an -OH group and a hydrogen (H) atom.

This process forms a new bond, called a peptide bond, between the carbon and nitrogen atoms.  Chains of amino acids are joined by peptide bonds; these chains are therefore also called polypeptide chains. Figure 3 shows an example of a polypeptide chain.  Polypeptide chains are then folded into proteins.  Note that Figure 3 uses a mixture of a structural and molecular formula; specifically, not all bonds to Hydrogen atoms are shown with a line.

The side chains give each amino acid a unique functionality. Examples of amino acids and their side chains are shown in Figure 3 in green.  Amino acids can be positively or negatively charged, water-repellent, bulky, bent into different configurations, or have other properties depending on their side chains. These differences help the polypeptides fold as they form proteins, bind to specific compounds, or chemically react in different ways.

Despite the fact that more than 500 amino acids exist on Earth, living things on Earth incorporate only 20 different amino acids to form the vast array of proteins that are used to regulate chemical reactions in all aspects of life. This is similar in spirit to the concept that even though the English languages only uses 26 letters, those same letters make up the words that compose millions of books.

It is commonly said that you are what you eat, but perhaps more correctly, you are what your proteins decide to do. Proteins are the driving force behind the processes of life. Many proteins act as enzymes, which are highly specified molecules that allow complicated organic reactions to progress more easily.

In most organic reactions, the molecules involved must first assume an unfavorable, intermediate configuration (see Figure 5 below) before progressing to the finished product. Enzymes bind to these starting molecules and act to stabilize the intermediary state. This makes it easier for molecules to progress to the desired final products. Enzymes are the primary why to increase reaction rates for biochemical processes.

In addition to acting as enzymes, proteins also fulfill several other important roles. Proteins are involved with cell signaling, which helps different cells in the body work together. Antibodies are proteins that work with the body’s immune system to recognize and destroy foreign substances that might cause illness. Structural proteins give shape or rigidity to cells, such as those that make up our nails or hair. Motor proteins allow for the movement of single-celled organisms. In short, proteins are critical for all of the basic functions of life.

Chirality of Amino Acids and Proteins

The central carbon in an amino acid can serve as a chiral center because it is typically bound to four different groups. Recall that chirality is defined as the property of an object that can not be superimposed on its mirror image, like how your palm-up hands cannot lay exactly on one another.  The one exception is the amino acid, glycine, whose hydrogen side chain makes it a symmetric molecule.

The chirality of amino acids means there exists both left-handed and right-handed amino acids (Figure 6 below). Oddly, while either configuration is possible, life on Earth only uses left-handed amino acids.

Studies have been done to investigate how the chirality of protein affects how it is made and performs. Synthesis of both left-handed and right-handed amino acids is not only possible, it is chemically equivalent. From an energy standpoint, protein that is composed entirely of right-handed amino acids should function just as well as proteins made of left-handed amino acids. The only difference is that using only one type of chirality could add an extra layer of regulation in biochemical reactions that may help to reduce synthesis errors.

How did life come to pick left-handed proteins over right-handed ones? There are many competing theories as to the origins of this inequality. One idea is that left-handed amino acids are slightly more water soluble (i.e., easier to dissolve in water), which could have made them easier to incorporate into early life.  Amino acids may also have been affected by the polarization of light.

Want to know more: Polarization

The polarization of light defines how the wave component of light oscillates relative to the direction in which the light is moving. Figure 7 shows light traveling from the bottom-right corner to the top-left corner.  It shows how the polarization of light can be (1) incoherent, as in the right-most third of Figure 7, (2) oscillate back and forth in only one direction, i.e., linearly polarized as in the center of Figure 7, or (3) circularly polarized as is shown in the first third of Figure 7. Different types of filters (shown in Figure 7 as blue squares) help give rise to these types of polarization. In the early Solar System, it is thought that dust grains could have caused all light to be circularly polarized.

It is possible that this circularly polarized light might have been more damaging to right-handed amino acids or more favorable to left-handed ones. Amino acids found in space, for example on meteorites, also exhibit an excess of left-handed molecules. If polarized sunlight gave rise to this imbalance, it could have tipped the scales to the left for life on Earth. Regardless of what established the original inequality, biological processes probably accentuated the imbalance.

Nucleic Acids to Genes

Nucleic acids are used throughout life on Earth to transfer genetic information during cell replication.  This genetic information defines the nature and structure of organisms.

Genes that are shared through cell replication and reproduction is why offspring look like their parents.  Differences in genetic information can give rise to differences in the traits of an organism.  For example, a change in genetic information may result an organism that is taller/shorter or fur color that is lighter/darker.

The process of gene replication—specifically gene mutation, which describes the errors that occur during gene replication—allow for different traits to arise.  Some traits may allow an organism to survive better in a given environment.  Lighter fur may be useful to blend in with a snowy environment; darker fur may be more helpful in a dark forest.

Organisms with these advantageous traits are more likely to be able to reproduce and pass on their favorable traits.  This process of natural selection allows organisms to adapt and evolve to different environments.  This ability to grow better equipped to surviving in an environment, also known as Darwinian evolution, is thought to be a key aspect of all living things.

Nucleotides

The nucleic acids found in all known living things on Earth take two forms: ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).  Nucleic acids are long, complex chains made up of nucleotides, a specific kind of molecule as diagramed in Figure 8.  Nucleotides consist of three components: (1) a central sugar, (2) an interchangeable base, and (3) a phosphate group.

RNA and DNA differ by the central sugar of the nucleotides that makes them up.  RNA uses ribose sugar while DNA uses deoxyribose sugar, which has one less oxygen molecule (note the atoms bonded to the 2nd carbon atom of each nucleotide shown in Figure 8).

The base of a nucleotide changes depending on the specific nucleotide, much like how different amino acids have different side chains.  In living things on Earth, five different bases are used.  RNA uses adenine, cytosine, guanine, and uracil (ACGU).  DNA also uses adenine, cytosine and guanine, but uses thymine in place of uracil (ACGT).  These bases bond to each other in specified ways.  Cytosine always binds to guanine.  Adenine bonds to the thymine in DNA and the uracil in RNA.

The structural formula for the five different bases are drawn in Figure 9.  Nucleotide bases fall into two categories: double-ringed purines (A,G) and single-ring pyrimidines (C, T, U).  Some of these bases were named after the material where they were first discovered. For instance, guanine was first discovered from guano, a fancy name for bird poop.

A phosphate group consists of a phosphorus atom bound to four oxygen atoms. This configuration contains many high energy bonds.  The energy stored in this phosphate group allows nucelotides to undergo the reaction that links nucleotides together to form the long-chain nucleic acids that are RNA and DNA.  These nucleic acids have a specific structure that was revealed only in the 1950s.

Want to know more: ATP – Cellular Energy Banks

An influx of energy is required to carry out many of the processes necessary for life.  You eat to enable your body to create stores of energy to use for these reactions.  You eat to create adenosine triphosphate, or ATP.

ATP, shown in Figure 10, is the most widely used energy carrier in all living organisms on Earth.  ATP is also a nucleotide consisting of (1) a ribose sugar, (2) an adenine base, and (3) three phosphate groups bonded in a chain.  When energy is needed for a chemical reaction, one of the high-energy phosphate to oxygen bonds in the chain is broken.  This converts ATP to ADP, adenosine diphosphate, where only two phosphate groups remain.

Phosphate groups are used across living organisms on Earth to supply the energy for necessary reactions.  Can you think of reasons why having a common source of energy across reactions would be beneficial?  (Hint: would you rather have different charging cables for each of your devices, or one common charging cable?)

How do we know: DNA’s structure

The exact structure of DNA was revealed through a series of insights that built on one another. When DNA was broken up into its constituent nucleotides, it was discovered that certain bases always appeared in the same proportions. The number of adenine and thymine nucleotides was always equal, and the number of cytosine nucleotides was always equal to the number of guanine nucleotides. In 1949, Erwin Chargoff, an Austro-Hungarian-born American biochemist, sought to explain this observation with the idea of base pairing—the idea that in DNA adenine is always bonded to thymine and cytosine is always bonded to guanine.

Observations of DNA using x-ray crystallography further revealed the structure of the molecule. X-ray crystallography is a complicated technique akin to shining a flashlight into a hall of mirrors and determining where the mirrors are placed based on the way that the light bounces around.

Rosalind Franklin, a British chemist, had a background in physical chemistry that she used to improved on x-ray crystallography techniques in the mid 1900s.  Franklin produced unprecedentedly precise x-ray crystallography images (see Figure 11) while working in the lab of Maurice Wilkins. Her most famous photo, known as “Photo 51”, held the key to DNA’s structure.  This photo was heralded by J.D. Bernal, the father of x-ray crystallography in biochemistry, as “among the most beautiful x-ray photographs of any substance ever taken.

The theoretical biochemists James Watson and Francis Crick used the idea of base pairing and Franklin’s images to reveal the double-helix structure of DNA. Watson discovered that the adenine-thymine bond was exactly the same length as the cytosine-guanine bond, which helped him form the picture of each base pair as rungs of a ladder. Crick helped to develop a mathematical model for the pattern that a helical structure would produce with x-ray crystallography.

In 1951, Crick and Watson began to work together.  When Maurice Wilkins showed them Rosalind Franklin’s Photo 51, they were able to piece together the double-helix model of DNA (see Figure 12).

 

The double-helix backbone of DNA is composed of the sugar and phosphate components of nucleotides. The bases stick out from this backbone and bind to their appropriate counterpart through weak hydrogen bonds. In the most common form, the bases appear parallel to each other, like a well-designed stairwell. The double-stranded nature of DNA affords a rigid, stable, and long-lived structure. During DNA replication, each strand is checked against the other to reduce copying errors or accidental mutations.

The genetic code in DNA is translated into instructions for how to manufacture proteins with the help of RNA. Messenger RNA (mRNA) transcribes the code from where DNA is located in the cell and carries this information to the ribosome.  Ribosomes are the molecules responsible for fabricating proteins in a cell.

A ribosome can read the genetic code from mRNA and translate it to the necessary amino acids to build a protein.  Ribosomes themselves are made up in part of RNA, known as ribosomal RNA (rRNA).  Each amino acid is specified by different codons, a sequence of three base pairs. Transfer RNA (tRNA) matches up each codon with the appropriate amino acid.  These different amino acids are bonded together into a polypeptide chain that can then be folded into the needed proteins.

The Genetic Code

To summarize, the cellular process of transcription generates messenger RNA (mRNA), a mobile molecular copy of one or more genes with an alphabet of A, C, G, and uracil (U). Translation of the mRNA template converts nucleotide-based genetic information into a protein product. Protein sequences consist of 20 commonly occurring amino acids; therefore, it can be said that the protein alphabet consists of 20 letters. Each amino acid is defined by a three-nucleotide sequence called the triplet codon. The relationship between a nucleotide codon and its corresponding amino acid is called the genetic code.

Given the different numbers of “letters” in the mRNA and protein “alphabets,” combinations of nucleotides corresponded to single amino acids. Using a three-nucleotide code means that there are a total of 64 (4 × 4 × 4) possible combinations; therefore, a given amino acid is encoded by more than one nucleotide triplet.

Three of the 64 codons terminate protein synthesis and release the polypeptide from the translation machinery. These triplets are called stop codons. Another codon, AUG, also has a special function. In addition to specifying the amino acid methionine, it also serves as the start codon to initiate translation. The genetic code is universal. With a few exceptions, virtually all species use the same genetic code for protein synthesis, which is powerful evidence that all life on Earth shares a common origin.

DNA encodes and stores genes, which describe a unit of genetic information.  Together, all the genes stored in DNA provide a very lengthy instruction manual for all living creatures on Earth. If you took the entire chain of DNA in one human cell and completely stretched it out, it would measure roughly 2 meters, the average height of an NBA player. If you took all of the DNA from all of the cells in a human body and joined them end-to-end, they would cross the diameter of the Solar System twice.

Different segments of DNA are known as chromosomes. An organism’s genome is the complete collection of chromosomes.  Humans have 23 pairs of chromosomes, encoding roughly 25,000 genes using about 3 billion base pairs. A mosaic of the entire human genome was sequenced between 1990 and 2008.  This monumental effort brought together twenty different institutions in six different countries. This remains one of the most impressive collaborative projects in science.

DNA encodes important instructions for life, but it can become damaged when base pairs or whole segments of DNA are deleted, inverted, duplicated, or moved around. Mutations can be damaging, for example, causing cells to become cancerous. Damage sustained to the phosphate-sugar backbone of DNA is one of the primary causes of mutations.  This type of damage is a common result of exposure to UV radiation, such as from the Sun (never skimp on sunscreen).

However, mutations can also occur naturally, resulting in expressed altered genes that give rise to new characteristics. This is the mechanism for Darwinian evolution: beneficial traits arising from mutation will be preferentially selected when mating and propagated through succeeding generations.

Natural mutations arise at measurable rates for different species. This mutation rate allows us to measure the genetic distance between species. This value is obtained by determining the statistical number of mutations required to change one species’ genome into another’s. For example, deer and giraffes are close in genetic difference, the genome of a deer requires relatively few differences to change into the genome of a giraffe when compared to, say, the genome of sunflowers.

The Last Universal Common Ancestor

The Last Universal Common Ancestor (LUCA) on Earth is a concept, rather than an actual organism. Any universal characteristics of life on Earth are universal either because they are inherited or because they are truly fundamental to life in general. Without a second example of life we are unable to understand how common these features will be on other worlds.

LUCA represents the earliest shared qualities of ancestral life and likely appeared on Earth between 3.5 to 4 Gya and seeded our planet with life. All of the features of life today would have been inherited from LUCA. From what we know about terrestrial biology, this means that LUCA would have been carbon-based, dependent on water, incorporated left-handed amino acids, and used ATP for energy transport. LUCA would have used DNA or RNA to encode genes and translate them into proteins. Significantly, the codons that translate for specific amino acids are the same in every known organism. This code must have been passed down from a common ancestor from which every other species has since evolved. LUCA might not have even been as sophisticated as a single celled organism.

The Tree of Life

The first instance of life was likely very simple and single-celled. Today, life is fantastically varied and complex. We separate the life we see today into three domains based on shared cellular structure and genetic material. The three domains of life, archaea, bacteria, and eukaryotes, are a diversification of the Last Universal Common Ancestor (LUCA).

• Bacteria make up the largest domain with both the greatest number of individual species and a biomass that exceeds the combined biomass of all plants and animals. Bacteria were one of the earliest forms of life on our planet and they are found in most habitats. Bacteria can rapidly recombine their genes with other bacteria to allow for genetic innovations, such as resistance to antibiotics.
• Archaea are genetically distinct from bacteria with their own, separate domain. Archaea are known to generate energy in a variety of ways and have been found in some of the most extreme environments on Earth. Halophiles, for example, exist in extremely salty conditions.
• Eukaryotes are distinct from prokaryotes in containing a central nucleus enclosed in a membrane and also contain other membrane-bound organelles. Examples of eukaryote organelles include chloroplast, the site of photosynthesis in plants and some algae, and mitochondria, where energy is generated in a cell. Eukaryotes can be uni- or multi-cellular, allowing for larger and more complex organisms.

Both bacteria and archaea are prokaryotes: single-celled microbes that do not contain membrane-bound organelles. However, the membranes in archaea incorporate a different type of lipid than either bacteria or eukaryotes. Genetic analysis reveals that archaea are closer to eukaryotes in an evolutionary sense than they are to bacteria. Archaea and eukaryotes use many of the same enzymes for DNA translation.

The Diversification of Life

Endosymbiosis

Eukaryotic cells have gained membrane-bound organelles and increased complexity through the process of endosymbiosis. Endosymbiosis is a process whereby primitive organisms benefited by living inside other organisms. Chloroplasts and mitochondria are examples of highly complicated organelles in eukaryotes that have their own membrane. They retained the DNA, messenger RNA, transfer RNA, and ribosomes of their bacterial ancestors before they were symbiotically incorporated into larger eukaryotic cells. The larger cell presumably provided protection and easy access to organic molecules while the chloroplast and mitochondria provided energy to the larger cell. This beneficial relationship led to the creation of larger, more efficient cells.

Cyanobacteria

The rise of oxygen likely began with organisms known as cyanobacteria, an early type of photosynthetic bacteria thought to be the first organism to produce oxygen as a byproduct. Photosynthesis is the process by which organisms can harness the energy of the sun to generate energy for their own use. Cyanobacteria are the only know prokaryotes to produce oxygen, and this adaptation brought about the destruction of many other organisms.

The rise in atmospheric oxygen was far from smooth and steady (see Figure 16 below). Cyanobacteria slowly became more abundant, but there was still a significant delay in the build up of oxygen. There are several processes that would have hindered the rise in oxygen. Oxygen would have reacted with various chemicals, mainly iron, in the oceans, and these reactions would trap oxygen, prevent it from building up the atmosphere.

Oxygen may also have been taken up by microbes in metabolic pathways that generate energy. Organisms that used the oxygen to oxidize ammonia appear to have been plentiful at the time and could have been effective in the reduction of free-floating oxygen. Other organisms produced methane as a byproduct that could have acted as a sink for atmospheric oxygen. However, organisms that are known to produce methane require nickel to carry out the necessary reactions, and concentrations of nickel were dropping. The decrease of nickel would mean less excreted methane, and would allow oxygen to begin accumulating.

The increase of oxygen in the atmosphere was poisonous for anaerobic organisms. Most life before the Great Oxidation Event was anaerobic, so the rise of atmospheric oxygen surely resulted in one of the most significant extinction events in Earth’s history. The fossil record shows a mass extinction of anaerobic life around 2.4-1.6 billion years ago, coincident with the rise of aerobic life.

Anaerobic vs Aerobic Life

The rise of atmospheric oxygen coincided with the appearance of far more complicated life forms. There is every reason to believe that the rise in oxygen would have been responsible since aerobic metabolisms are more efficient.

Respiration, in biological terms, describes the process by which organisms convert nutrients into usable energy by forming ATP bonds. Respiration begins with glycolysis, wherein glucose, a sugar, is broken down to form two molecules of a compound called pyruvate along with two molecules of ATP. Without oxygen, organisms have no choice but to undergo anaerobic respiration, or fermentation. Anaerobic respiration of yeast is what makes bread rise and beer bubbly. In this scenario, pyruvate is shuttled down a pathway which produces just two molecules of ATP.

In the presence of oxygen, aerobic respiration becomes possible. With the help of oxygen, pyruvate can be broken down and enters a more complicated pathway known as the Krebs cycle or the citric acid cycle (note that organisms exhibit an enormous variety of metabolic pathways; the citric acid cycle merely represents one of the more common and well understood pathways). Through the citric acid cycle, organisms can produce from 30–36 ATP from just one molecule of glucose. Though more complicated to assemble, and therefore likely taking longer to evolve, this process can be up to 18-fold more efficient than anaerobic respiration. With more energy, it is possible to carry out more biochemical processes. This may have allowed cells to become increasingly complex and trend towards the more varied, multicellular life we see today.

Want to know more: Viruses

Viruses are even more abundant than bacteria. A virus consists of three functional parts: (1) genetic material, (2) protein coat, and typically (3) an envelope of lipids outside the protein coat. For genetic material, viruses have been discovered to use both DNA and RNA. The protein coat, also known as the capsid, encases and protects this genetic material. The envelope of lipids adds an additional layer of protection.

However, the question of whether viruses can be considered life is hotly debated. Viruses have their own genetic material and are even capable of evolving through natural selection. Viruses survive and replicate by infecting a host cell. After attaching to a cell, the virus injects its DNA into the host cell. Now, the virus is capable of taking over the host cell’s replication mechanisms. In doing so, the virus can now create copies of itself until it has exhausted the cell’s resources. Millions of viruses can be made in this period before the cell dies and viruses escape to infect new host cells. Because viruses require the metabolism of a host cell to produce energy and reproduce, they can not be called self-sustaining. In this way, viruses fail the NASA definition of life.

Despite their differences, evidence of viruses appear wherever life does, suggesting that viruses and life evolved together.  The history of viruses is traced through their DNA or RNA and has given rise to three theories on how viruses came to be.

Regressive evolution theory proposes that viruses were once components of small, parasitic cells. Similar to the idea of endosymbiosis, viruses may have begun as small structures within larger cells that over time became separated. In fact, there exist today some bacteria that, like viruses, can only reproduce in a host cell. As they evolved, these small parasitic structures regressed further from cell-like characteristics, becoming the viruses we see today. However, there is no evidence of types of cells today that could serve as an intermediary between early and present day viruses. Even the smallest cellular parasites fail to really resemble viruses at all.

Another theory is the escaped gene theory, which proposes that viruses got their start as DNA or RNA that escaped from the genome of a larger organism. Surprisingly mobile DNA has recently come to play a large role in biology. Plasmids (Figure below) are circular units of DNA and separate from the genome of an organism. They are most commonly found in bacteria and have been known to move between cells. Scientists have also recently discovered transposons, or “jumping genes,” which are large segments of DNA that can move around within a cell’s genome. While either of these mechanisms could have provided the genetic material for viruses, it remains unclear where the complicated capsids enclosing these genes arose from.

The pre-cellular origin theory proposes that viruses formed from complex proteins that spontaneously arose even before RNA. Viruses could have evolved alongside the first cells or even before. However, this fails to account for the dependency viruses have on host cells. If viruses need the mechanism of a host cell to survive, how did they manage before cells even evolved?

The exact origin of viruses, much like the origin of life, remains an open question. This vein of research is being pushed forward through analysis of viral and host DNA sequences. What we can say is that genetic comparisons show that the origins of viruses may have predated life splitting into the three different domains. Perhaps the precursors to viruses evolved from the self-replicating molecules that dominated the RNA world. Similar to RNA, viruses are capable of self-assembling in host cells.

Viruses are now well enough understood to be used as tools in biomedical research. In a process called gene therapy, researchers use viruses to inserting genes into specific cells, offering possible treatments for diseases like cystic fibrosis. Some viruses will seek out and destroy cancer cells, while leaving healthy cells alone, allowing for a highly targeted and effective treatments.