- Describe the requirements for the origin of life (carbon source, energy, segregate molecules from environment, hereditary mechanism)
- Describe the steps which led to the origin of life (organic molecules form, macromolecules polymerize, a hereditary mechanism develops, membrane-enclosed protocells form).
- Apply the principles of evolution by natural selection to pre-biotic scenarios.
The origin of life is a mystery, the ultimate chicken-and-egg conundrum (R Service, 2015). When you and fellow students together discussed the defining characteristics of life, you probably included reproduction and hereditary information, transformation of energy, growth and response to the environment. You may also have said that, at least on Earth, all life is composed of cells, with membranes that form boundaries between the cell and its environment, and that cells were composed of organic molecules (composed of carbon, hydrogen, nitrogen, oxygen, phosphate, and sulfur – CHNOPS). The conundrum is that, on Earth today, all life comes from pre-existing life. Pasteur’s experiments disproved spontaneous generation of microbial life from boiled nutrient broth. No scientist has yet been able to create a living cell from organic molecules. So how could life have arisen on Earth, around 3.8 billion years ago? (Keep in mind the scale of time we’re talking about here – the Earth is 4.6 billion years old, so it took almost a billion years for chemical evolution to result in biological life.) How can this question be addressed using the process of scientific inquiry?
Origin of life studies
Although scientists cannot directly address how life on Earth arose, they can formulate and test hypotheses about natural processes that could account for various intermediate steps, consistent with the geological evidence. In the 1920s, Alexander Oparin and J. B. S. Haldane independently proposed nearly identical hypotheses for how life originated on Earth. Their hypothesis is now called the Oparin-Haldane hypothesis, and the key steps are:
- formation of organic molecules, the building blocks of cells (e.g., amino acids, nucleotides, simple sugars)
- formation of polymers (longer chains) of organic molecules, that can function as enzymes to carry out metabolic reactions, encode hereditary information, and possibly replicate (e.g., proteins, RNA strands),
- formation of protocells; concentrations of organic molecules and polymers that carry out metabolic reactions within an enclosed system, separated from the environment by a semi-permeable membrane, such as a lipid bilayer membrane
The Oparin-Haldane hypothesis has been continually tested and revised, and any hypothesis about how life began must account for the 3 primary universal requirements for life: the ability to reproduce and replicate hereditary information; the enclosure in membranes to form cells; the use of energy to accomplish growth and reproduction.
1. How did organic molecules form on a pre-biotic Earth?
Stanley Miller and Harold Urey tested the first step of the Oparin-Haldane hypothesis by investigating the formation of organic molecules from inorganic compounds. Their 1950s experiment produced a number of organic molecules, including amino acids, that are made and used by living cells to grow and replicate.
Miller and Urey used an experimental setup to recreate what environmental conditions were believed to be like on early Earth. A gaseous chamber simulated an atmosphere with reducing compounds (electron donors) such as methane, ammonia and hydrogen. Electrical sparks simulated lightning to provide energy. In only about a week’s time, this simple apparatus caused chemical reactions that produced a variety of organic molecules, some of which are the basic building blocks of life, such as amino acids. Although scientists no longer believe that pre-biotic Earth had such a reducing atmosphere, such reducing environments may be found in deep-sea hydrothermal vents, which also have a source of energy in the form of the heat from the vents. In addition, more recent experiments – that used conditions that are thought to better reflect the conditions of early Earth – have also produced a variety of organic molecules including amino acids and nucleotides (the building blocks of RNA and DNA) (McCollom, 2013).
The video below gives a nice overview of the rationale, setup, and findings from the Miller-Urey experiment (although it incorrectly overstates that Darwin showed that relatively simple creatures can gradually give rise to more complex creatures).
Organic molecules from meteors
Each day the Earth is bombarded with meteorites and dust from comets. Analyses of space dust and meteors that have landed on Earth have revealed that they contain many organic molecules. The in-fall of cometary dust and meteorites was far greater when the Earth was young (4 billion years ago). Many scientists believe that such extra-terrestrial organic matter contributed significantly to the organic molecules available at the time that life on Earth began. The figure below from Bernstein 2006 shows the 3 major sources of organic molecules on pre-life Earth: atmospheric synthesis by Miller-Urey chemistry, synthesis at deep-sea hydrothermal vents, and in-fall of organic molecules synthesized in outer space.
2. Formation of organic polymers
Given a high enough concentration of these basic organic molecules, under certain conditions these will link together to form polymers (chains of molecules covalently bonded together). For example, amino acids link together to form polypeptide chains, that fold to become protein molecules. Ribose, a 5-carbon sugar, can bond with a nitrogenous base and phosphate to a nucleotide. Nucleotides link together to form nucleic acids, like DNA and RNA. While this is accomplished now by enzymes in living cells, polymerization of organic molecules can also be catalyzed by certain types of clay or other types of mineral surfaces. Experiments testing this model have produced RNA molecules up to 50-units long, in only a 1-2 week period of time (Ferris, 2006).
Enzymatic activity and hereditary information in one polymer: the RNA World hypothesis
The discovery by Thomas Cech that some RNA molecules can catalyze their own site-specific cleavage led to a Nobel prize (for Cech and Altman), the term “ribozymes” to denote catalytic RNA molecules, and the revival of a hypothesis that RNA molecules were the original hereditary molecules, pre-dating DNA. For origin-of-life researchers, here was the possibility that RNA molecules could both encode hereditary information, and catalyze their own replication. DNA as the first hereditary molecule posed real problems for origin-of-life researchers because DNA replication requires protein enzymes (DNA polymerases) and RNA primers (see page on DNA replication), so it’s difficult to envision how such a complex hereditary system could have evolved from scratch. With catalytic RNA molecules, a single molecule or family of similar molecules could potentially store genetic information and replicate themselves, with no proteins needed initially.
Populations of such catalytic RNA molecules would undergo a molecular evolution conceptually identical to biological evolution by natural selection. RNA molecules would make copies of each other, making mistakes and generating variants. The variants that were most successful at replicating themselves (recognize identical or very similar RNA molecules and most efficiently replicate them) would increase in frequency in the population of catalytic RNA molecules. The RNA world hypothesis envisions a stage in the origin of life where self-replicating RNA molecules eventually led to the evolution of a hereditary system in the first cells or proto-cells. A system of RNA molecules that encode codons to specify amino acids, and tRNA-like molecules conveying matching amino acids, and catalytic RNAs that create peptide bonds, would constitute a hereditary system much like today’s cells, without DNA.
At some point in the lineage leading to the Last Universal Common Ancestor, DNA became the preferred long-term storage molecule for genetic information. DNA molecules are more chemically stable than RNA (deoxyribose is more chemically inert than ribose). Having two complementary strands means that each strand of DNA can serve as a template for replication of its partner strand, providing some innate redundancy. These and possibly other traits gave cells with a DNA hereditary system a selective advantage so that all cellular life on Earth uses DNA to store and transmit genetic information.
Still, even today, ribozymes play universal and central roles in cellular information processing. The ribosome is a large complex of RNAs and proteins that reads the genetic information in a strand of RNA to synthesize proteins. The key catalytic activity, the formation of peptide bonds to link two amino acids together, is catalyzed by a ribosomal RNA molecule. The ribosome is a giant ribozyme. Since ribosomes are universal to all cells, such catalytic RNAs must have been present in the Last Universal Common Ancestor of all current life on Earth.
Visit the http://exploringorigins.org/ribozymes.html page to view the first ribozyme from Tetrahymena, discovered by Tom Cech, and the structure of the ribosomal RNAs.
The http://exploringorigins.org/nucleicacids.html page has videos of polymerization of RNA from nucleotides, template-directed RNA synthesis, and a model of RNA self-replication.
The video below explains the rationale behind the RNA world hypothesis and briefly describes some of the findings from different RNA world experiments.
3. Protocells: self-replicating and metabolic enzymes in a bag
All life on Earth is composed of cells. Cells have lipid membranes that separate their inner contents, the cytoplasm, from the environment. The lipid membranes allow cells to maintain high concentrations of molecules like nucleotides needed for self-replicating RNAs to function more efficiently. Cells also maintain large differences in concentration (concentration gradients) of ions across the membrane to drive transport processes and cellular energy metabolism.
Lipids are hydrophobic, and will spontaneously self-assemble in water to form either micelles or lipid bilayer vesicles. Vesicles that enclose self-replicating RNAs and other enzymes, take in reactants across the membrane, export products, grow by accretion of lipid micelles, and divide by fission of the vesicle, are called proto-cells or protobionts and may have been the precursors of cellular life.
See http://exploringorigins.org/protocells.html for video animations of proto-cells.
The video below explores the differences between chemical and biological evolution, and highlights proto-cells as an example of chemical evolution.
At what point would evolutionary processes, such as natural selection, begin to drive the origin of the first cells?
Biological evolution is restricted to living organisms. So once the first cells, complete with a hereditary system, were formed, they would be subject to evolutionary processes, and natural selection would drive adaptation to their local environments, and populations in different environments would undergo speciation as gene flow becomes restricted between isolated populations.
However, the RNA World Hypothesis envisions evolutionary processes driving populations of self-replicating RNA molecules or proto-cells containing such RNA molecules. RNA molecules that replicated imperfectly would produce daughter molecules with slightly different sequences. The ones that replicate better, or improve the growth replication of their host proto-cells, would have more progeny. Hence, molecular evolution of self-replicating RNA molecules or proto-cell populations containing self-replicating RNA molecules would favor the eventual formation of the first cells.
References and Resources
Article on HCN chemistry by Patel et al. 2015 with Science News article by R. Service.
Bernstein M 2006. Prebiotic materials from on and off the early Earth. Philos Trans
R Soc Lond B Biol Sci. 361:1689-700; discussion 1700-2. PubMed
PMID: 17008210; PubMed Central PMCID: PMC1664678.
Exploring Life’s Origins: http://exploringorigins.org/index.html
Here’s a link to a fun article on work by Georgia Tech’s Nick Hud using a $5 toaster oven for his origin-of-life research!
Thanks to Timothy for the find and the link
New paper reveals likely traits of the Last Universal Common Ancestor of all extant life:
Weiss et al. 2016: The physiology and habitat of the last universal common ancestor, Nature Microbiology 1, Article number: 16116 doi:10.1038/nmicrobiol.2016.116
James McInerney wrote a brief commentary for the above article: http://www.nature.com/articles/nmicrobiol2016139
text in blue added in response to student questions, 11/2/2016
Fantastic (somewhat long) retelling of origin-of-life research, with the twist and turns, culminating with the current integrated hypotheses.
A new paper going beyond the Miller-Urey types of expts to explore what could emerge out of these prebiotic chemistries: Wolos et al 2020, Synthetic connectivity, emergence, and self-regeneration in the network of prebiotic chemistry