ACTION BIOSCIENCE

December 2000

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Scanning electron micrograph of Escherichia coli bacteria. Source: Rocky Mountain Laboratories, NIAID, NIH

For as long as we have known about them, scientists have thought that simple bacteria were the link to the earliest life forms on earth. However, growing evidence suggests we’ve got it all back to front — could the secrets of the origin of life be lurking inside us?

Scientists used to think that life evolved from the simple bacteria.

When most of us think about evolution, we tend to think in terms of simple organisms evolving into more complex ones. Simple chemical reactions evolved into simple cells, which later evolved into more complex organisms, and so on all the way up to humans. It’s no longer believed that humans are at the top of the evolutionary ladder, but evolution does tend to drive organisms towards greater complexity, does it not?

Human cells tell more about evolution than bacteria.

However, this is not always so. Rather, those organisms that leave the most offspring behind, simple or complex, do best. Greater complexity is sometimes a consequence of evolution, but simplification can also be a winning strategy — it all depends on the environment. Nevertheless, most scientists hold that the first organisms on Earth were much like bacteria of today. But several features of the biochemistry of life suggest that bacteria aren’t so ancient after all. In fact, in some respects, the cells of our own bodies tell us more about the evolution of life than bacteria do. The key is in the discovery that won Sidney Altman and Tom Cech the Nobel Prize in Chemistry in 1989.

The chicken and the egg

DNA can reveal evolutionary history, i.e., the story of life.
  • In modern organisms, genetic information is stored on DNA (deoxyribose nucleic acid) in units called genes.
  • Genes code for proteins, which are responsible for the various activities that make a cell function.
  • Some proteins, called enzymes, perform the chemical reactions that run the cell. One group of enzymes, the DNA polymerases, make DNA.
  • The information for making those enzymes is stored in the DNA as a gene.

Therefore, finding the evolutionary origin of proteins and DNA is tricky as each requires the other for its own synthesis-which came first? That’s where Cech and Altman come in. They studied RNA (ribose nucleic acid), a close chemical relative of DNA:

Some scientists believe that RNA, not proteins or DNA, acted as starting material for life.
  • When proteins are made from the information in DNA, a working RNA copy of the gene is made for use by ribosomes, the protein factories of the cell. Therefore RNA, like DNA, stores genetic information, and, like proteins, it also performs chemical reactions.
  • Bringing RNA into the picture solves the chicken and egg problem. RNA can be both chicken and egg.
  • What this means to evolutionary biologists is that life could well have BEGUN with organisms made largely of RNA.
  • This idea of an ‘RNA world’ has been debated since the 1960’s, but Cech and Altman’s discovery has convinced most scientists that it is at least possible.
  • It is now known that RNA is at the heart of many of the basic functions in the cell, and probably evolved in the RNA world.

Jack-of-all-trades

But if RNA is so versatile, what happened to the ‘RNA world’? As the saying goes, “Jack-of-all-trades, master of none;” RNA is not as good at performing chemical reactions as proteins, nor is it as good at storing genetic information as DNA. It’s not surprising that since the RNA world, proteins have gradually replaced most RNA enzymes, and DNA now stores the genetic information.

Can modern cells tell us which came first — proteins, RNA, or DNA?

Most researchers agree that RNA used to have more of a central role because it solved the chicken-and-egg problem of which came first in evolution- proteins or DNA. But other than being a tidy piece of logic, is there any substance to the hypothesis? Since we can’t travel back in time, it is impossible to prove the existence of the RNA world outright, but we can do the next best thing-rebuild it from the ‘molecular fossils’ that have remained in modern cells.

Looking for ‘molecular fossils’

By delving into our RNA-rich past, we can get an idea of what early life looked like, and this may in turn help us understand how life evolved into the many forms we see today. ‘Digging’ for molecular fossils is not a trivial exercise. Not all RNAs are going to be genuine RNA world fossils, but it is possible to establish which are likely to be ancient, and which are more recent additions.

RNA in ribosomes may provide clues to cellular origins.
  • One of the most central machines in the cell is the ribosome, which translates the genetic code stored in DNA into the language of proteins.
  • The core of the ribosome is made from RNA, with proteins providing a scaffold to hold the RNA in place. Even with most of the protein stripped away, it can still make proteins.
  • The finding that the RNA core is the engine room of the protein synthesis factory is a strong argument that protein synthesis was invented in the RNA world.

Indeed, the ribosome is just one of many RNA machines, giving scientists a surprisingly clear picture of early life. The picture appears most complete in the eukaryotes (plants, animals, fungi, amoebae), which are more reliant on RNA than prokaryotes (bacteria and related cells), the former retaining more clues to our RNA-rich past. Since RNA is a Jack-of-all-trades we would expect it to be gradually replaced during evolution.

Simple organisms may be more evolved than complex ones.

The common view of the evolution of eukaryotes and prokaryotes from an ancient ‘last universal common ancestor’ (the LUCA), is that a prokaryote-like creature was the first to arise, and that an ancient eukaryotes arose from some prokaryote:

RNA world → LUCA → prokaryote-like organism → eukaryote-like organism

Since many more ancient RNA world fossils are found in eukaryotes, the graph makes more sense this way, with a gradual loss of RNA:

RNA world → LUCA → eukaryote-like organism → prokaryote-like organism

Backing up the hard drive

In addition to the information we can glean from the study of RNA, we can also learn about our evolutionary past by examining how the storage of genetic information has evolved. Genetic information is like any other information; it is stored in a particular medium, it gets copied, read and transmitted, and over time, small errors can turn up.

Cells without nuclei (prokaryotes) store genetic information differently than cells with nuclei (eukaryotes).

Prokaryotes and eukaryotes employ quite different mechanisms for ensuring that genetic information is not corrupted. The differences are as follows:

  • Prokaryotes maintain their genome in a single copy, usually a single DNA chromosome, with as much information packed onto it as possible.
  • Many eukaryotes have two copies, divide the information up into several DNA chromosomes, with the genes packed relatively sparsely. Unlike prokaryotes, eukaryotes keep backup copies.
  • Having only one copy of a gene means that if an error is made, that damage is permanent-there is no backup copy for its rescue.

But what difference does it make if the genes are split up or kept on a single chromosome? Consider this example:

Without a backup for genetic data, errors in the genome become permanent.
  • Genome 1 has two genes, A and B. These are housed on a single chromosome, and there are two copies of that chromosome. In one copy, gene A gets damaged and in the other, gene B gets damaged. The organism can still survive because it still has one working copy of gene A and one working copy of gene B. However, it has to carry the damaged copies also, because these are physically linked (on the same chromosome) to the working copies.

  • Genome 2 also has two genes, A and B. However, each gene is housed on its own chromosome, and again there are two copies of each chromosome. Again, one copy of gene A gets damaged, and one copy of gene B gets damaged. However, genome 2 can discard the damaged copies of genes A and B without losing the working copies, as each gene has its own chromosome.

Genome ‘architecture’ gives us a clue as to the informational stresses on a genome: the more genes that are kept together on a single chromosome, the greater the accuracy required to maintain them.

  • In early genetic systems, the strategy described for genome 2 was probably used because damage was frequent, and this provided a good way of discarding damaged genes while keeping the undamaged copies.

  • The more copies of a genome and the fewer genes per chromosome, the better this would work.

Prokaryotes are considered risk takers because they lack the safety nets of eukaryotes.
  • Prokaryotes appear to use none of these safety nets, so can be considered risk takers.

  • Prokaryote genomes thus look like a recent invention-organisms could only afford to keep one copy of their information on a single chromosome if they were pretty sure they would not lose it.

  • Early life forms were not good at storing information, especially since they had RNA as a genetic material. They needed to develop as many little tricks as possible to minimize mutation; genomes like those in prokaryotes would have been disastrous!

  • Perhaps eukaryotes (for example, plants & animals) never lost many of these ancient traits left over from a period where copying was poorer, so their genomes can be considered fossils of this earlier period in the evolution of life.

  • Interestingly, many single-celled eukaryotes maintain their DNA as a single copy. It is therefore hard to know if ancestral eukaryotes maintained one or more copies of their genome.

  • Keeping back-up copies was nevertheless an essential trait in very early genetic systems.

The tortoise & the hare

Looking at both the RNA relics in eukaryotes and their genome design, it appears eukaryotes have maintained the status quo, retaining many molecular fossils, while prokaryotes have lost many of these. How might this have happened? It could well be due to ‘lifestyle’ — the ways in which organisms go about their daily business:

  • Some organisms (e.g., oak trees) are slow growing and rely on a stable supply of nutrients, making their populations fairly stable also.
  • Other organisms (e.g., locusts) grow very fast and compete for nutrients that are extremely variable in supply. When a nutrient is available, it is crucial to grow and reproduce as fast as possible. When the food supply runs low, the populations suffer large crashes and only a few make it to the next nutrient source.
Ability to adapt to environmental changes enhances an organism’s chance of survival.

For some organisms, speed is everything — the ability to react quickly to the presence of a new food source is all-important. This means that if one organism is faster to respond than the rest, it will profit at the expense of its competitors. Thinking back to the ancient RNA machinery, there would have been strong selection in organisms to replace inefficient RNA machinery with faster protein machinery.

In modern organisms, eukaryotes as a group fit into the ‘Tortoise’ group, while the prokaryotes take the fast ‘hare’ track, but within these, there is also a spectrum-brewer’s yeast has a ‘bacterial lifestyle’ when compared to oak trees for example. However, even fast-growing eukaryotes have a lot of slow RNA machinery, so this argument alone may not explain how prokaryotes arose. If a fast lifestyle alone doesn’t shed RNA, then how do we explain the lack of RNA in prokaryotes?

Shedding the excess in life’s sauna

The evolutionary ‘push’ that gave rise to the prokaryotes may well have been an adaptation to living at high temperatures. Patrick Forterre, at the University of Paris Sûd has put forth a hypothesis which he calls the ‘thermoreduction hypothesis.’ He maintains that prokaryotes arose from a eukaryote-like ancestor by adaptation to life at high temperatures, and in the process shed many of their ancient features. Forterre’s work suggests that even the bacteria now living at moderate temperatures retain traces of their hot history.

Forterre’s argument rests on the observation that RNA is very unstable at high temperatures:

Some prokaryotes have adapted to life at extreme temperatures, such as deep sea vents.
  • Organisms living at high temperatures should make limited use of RNA.
  • In prokaryotes, many RNA fossils appear to have been replaced.
  • Numerous prokaryotes live in the scalding hot temperatures typical of hot springs and deep sea thermal vents, which often exceed 100°C!
  • In eukaryotes, many RNAs are still in use.
  • Currently there are no known examples of eukaryotes living at extreme temperatures. If any are found, we would expect them to have lost a lot of their RNA.
Prokaryotes can survive in higher temperatures because, unlike eukaryotes, their DNA is in a protective circular configuration.

Another piece of evidence for thermoreduction comes from the genomes of prokaryotes:

  • In eukaryotes, chromosomes are made of linear DNA.
  • In prokaryotes the genome is made of circular DNA.
  • Circular DNA is much less vulnerable to heat damage than linear DNA, which starts to get ‘split ends’ at high temperatures.
  • Circular chromosomes are conspicuously absent from eukaryotes and their widespread incidence in prokaryotes alone is best explained by the thermoreduction hypothesis.

For eukaryotes to maintain linear DNA genomes, they require a special system for maintaining their ends:

  • An enzyme called telomerase, which has both a protein and an RNA component, does this job.
  • Telomerase is common to all eukaryotes, suggesting it is very ancient.
  • It seems unlikely that eukaryotes with their linear genomes, and many RNAs, including telomerase, could have emerged from the ‘sauna’ of life.
  • It is more likely that the organisms which first braved high temperatures shed much of the evidence of their RNA world ancestry along the way, as well as linear DNA genomes and telomerase.
  • Modern prokaryotes appear to have a ‘hot history,’ even though many now live at moderate or even cold temperatures.

Clues to the origin of life in your own body

Evolutionary biologists have traditionally studied the simplest organisms they can find in order to learn more about the origins of life. But simple doesn’t necessarily mean ancient, so we should not restrict our search purely to simple organisms. All organisms have been evolving for 3.5 billion years or so, and the idea that there is some obscure bug that time forgot which resembles ancient life on Earth is outdated.

Human cells, which are eukaryotic, may harbor secrets to the origin of life.

As Forterre’s work shows, simplification has its merits, and it seems that bacteria have lost a lot of the molecular fossils of our ancient past. We know an enormous amount about the biochemistry of our own cells, and although there’s layer upon layer of complexity, hidden underneath it all are clues to the origins of the earliest cells. How ironic it is that human cells harbor as many if not more secrets of the origins of life than the simple bacteria! It’s no wonder that evolutionary biologists are as excited about the Human Genome Project as anyone else!

The cell’s nucleus may be a more ancient development than first thought.

It is important to keep in mind that eukaryotic cells have continued to evolve over time. While it is possible to uncover much about the RNA world, and how prokaryotes and eukaryotes evolved by looking at ‘molecular fossils’, most features of the eukaryotic cell are ‘recent’ innovations. For instance, mitochondria (the power plant of the eukaryotic cell) and chloroplasts (the organelle which sunlight turns into sugar in plants) are the remnants of ancient prokaryotes that were engulfed by ancient eukaryotes. Another major innovation is the evolution of multicellular organisms. This brought with it the fruits of division of labor, allowing the evolution of complex organs and tissues.

Conclusion: Molecular fossils may change some scientific views about the origins and evolution of life.

Most researchers would add the nucleus to the list of ‘new’ eukaryotic features, but its interesting to note that all RNA world fossils are found in the nucleus. The assumption that the nucleus is recent is based on the argument that evolution drives towards complexity, but we know this isn’t always so. It is exciting to consider the possibility that the nucleus is old, and prokaryotes have lost it.

Once upon a time, we’d probably have been in danger of being burnt at the stake for such heretical stuff, but nowadays biologists no longer view the evolution of life as a progression from simple to complex with humans as the pinnacle of evolutionary achievement. Here’s to your molecular fossils!

Daniel Jeffares, Ph.D., works at the Department of Evolutionary Biology, University of Copenhagen, Denmark. His interests center around the evolution of the ‘molecular machinery’ of cells. He is studying the evolution of small nucleolar RNAs, with Anthony Poole, and examining alternative splicing of messenger RNA in the nematode C. elegans using microarrays. He received his Ph.D. in Plant Development from Massey University, New Zealand.
http://www.zi.ku.dk/evolbiology/staff/scientific.asp

Anthony Poole received his Ph.D. from Massey University, New Zealand. He did a postdoc at the Allan Wilson Centre for Molecular Ecology & Evolution, before moving to Stockholm University, on a Swedish Research Council-funded Assistant Professorship, then as a Royal Swedish Academy of Sciences Research Fellow. His research to date has centered around questions in early evolution, and his current focus is on the origins of DNA and the evolution of the eukaryote cell. He is currently based at the University of Canterbury http://www.biol.canterbury.ac.nz/people/poole.shtml

Were Bacteria the First Forms of Life on Earth?

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Understanding Evolution

Your one-stop source for information on evolution. Learn the facts in Evolution 101, browse the resource library, read about evolution in the news, or discover a wealth of materials to help educate others about evolution and related concepts—it’s all right here! http://evolution.berkeley.edu

Life in ocean extremes

Discovery network provides pictures of some of the creatures that live in and around the extreme environment of deep sea vents.
http://dsc.discovery.com/convergence/blueplanet/photo/photo.html

The Origin of Life on Earth

Learn more about the RNA world and the current and historical ideas on the origin of life on Earth by reading this thought provoking article by Leslie Orgel of the Salk Institute for Biological Studies.
http://www.geocities.com/CapeCanaveral/Lab/2948/orgel.html

The Tree of Life page

A fun, interactive site that lets you surf up and down “The Tree of Life.”
http://tolweb.org/tree/

Human genome project information

Explore this comprehensive site, sponsored by the U.S. Department of Energy’s Office of Science, for information about the U.S. and worldwide Human Genome Project. Second link takes you to their Primer on Molecular Genetics to learn more about DNA and sequencing.
http://www.ornl.gov/hgmis/
http://www.ornl.gov/sci/techresources/Human_Genome/publicat/primer/toc.html

Eukaryotic Origins

Astrobiology Magazine article examines endosymbiosis (how bacteria is engulfed).
http://www.astrobio.net/pressrelease/3223/endosymbiosis-timeline

Further reading (science journals)

  • » Doolittle W.F. 2000. “The nature of the universal ancestor and the evolution of the proteome.” Current Opinion in Structural Biology 10:355-358.
  • » Forterre P., Philippe H. 1999. “Where is the root of the universal tree of life?” BioEssays 21:871-879.
  • » Penny D., Poole A. 1999. “The nature of the last universal common ancestor.” Current Opinion in Genetics and Development 9:672-677.
  • » Poole A., Jeffares D., Penny D. 1999. “Early evolution: prokaryotes, the new kids on the block.” BioEssays 21:880-889.
  • » Ridley M. 2000. “The search for LUCA.” Natural History 11:82-85.

The RNA Society

Biology students and scientists can join this scientific society to share research results and information about emerging concepts in RNA. Membership application is available on-line. There is a sliding membership fee.
http://www.rnasociety.org

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Teaching Resources from the Northwest Association for Biomedical Research (NWABR)

The Northwest Association for Biomedical Research (NWABR) strengthens public trust in research through education and dialogue. Its diverse membership spans academic, industry, non-profit research institutes, health care, and voluntary health organizations. Through membership and extensive education programs, it fosters a shared commitment to the ethical conduct of research and ensures the vitality of the life sciences community.

Advanced Bioinformatics: Genetic Research
This curriculum unit explores how bioinformatics is used to perform genetic research. Students examine DNA sequences from different animal species, investigate the relationship between protein structure and function, and explore evolutionary relationships among eukaryotic organisms. Throughout the unit, students are presented with a number of career options in which the tools of bioinformatics are developed or used.
http://www.nwabr.org/curriculum/advanced-bioinformatics-genetic-research

Origin of life lessons

Interactive lessons focus on origin of life studies. These lessons are intended for use in any high school biology course but many can be used in middle school, junior college or lower division university levels.
http://www.indiana.edu/~ensiweb/orig.fs.html

Bacteria

Interactive online learning module about bacteria, complete with quiz questions. The second link takes you to an in-depth look at the different types of bacteria, with information about each group. http://www.childrensuniversity.manchester.ac.uk/interactives/science/microorganisms/whatarebacteria.asp http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/E/Eubacteria.html

Can Bacteria Arise from Non-Living Things?

This lesson is a lab activity in which students work in groups to solve the problem: can bacteria arise from non-living things? High School.
http://www.beaconlearningcenter.com/Lessons/2211.htm

General References:

author glossary

Chromosome - A single length of DNA which contains many genes. Eukaryotes have several different linear chromosomes in each cell, and each contains some of the genes cells need for life (humans have 23). Prokaryotes usually have one circular chromosome, which contains all their genes.

DNA - Deoxyribose nucleic acid (DNA) is built up of four types of units, adenine (A), guanine (G), cytosine (C) and thymine (T), joined in a series. Genes are encoded by the specific sequence of the DNA, and their products are usually proteins. For example, the sequence ATG indicates the start point of a gene, and tells the cell that the first amino acid in the protein is methionine.

DNA polymerases - A class of enzyme that synthesises DNA.

Enzyme - Enzymes speed up (catalyse) chemical reactions. Most enzymes are proteins but a few are made from RNA.

Eukaryotes - Have cells with a nucleus that contains all the DNA. Eukaryotes include plants, animals, fungi, amoeba, algae, and many other organisms. Eukaryotes can be multicellular (many-celled) or single celled. Compare with prokaryotes.

Genetic code - The language of genes. Three nucleotides together make a codon which codes for an amino acid. For example GAG codes for the amino acid glutamine. Ribosomes read the codons from an RNA copy of a gene, joining amino acids together to make the protein encoded in that gene. The genetic code is the same for all living things.

Genome - The collection of genes that make up an organism. These genes may be on one chromosome, or many.

Prokaryotes - Do not have a nucleus. There are two groups: bacteria and archaea, which appear quite different from each other. All prokaryotes are single celled.

Protein - A chain of amino acids. The sequence of amino acids is specified by a gene. Each protein is made by a ribosome, and it folds up into a specific shape that is determined by the sequence of amino acids. The precise arrangement of amino acids determines the properties of the protein. Some proteins are enzymes.

Ribosomes - Ribosomes are the cell’s protein factories. Ribosomes read the genetic code from the working RNA copies of genes, using these to synthesise the protein encoded by the gene. Ribosomes have an RNA core, which is largely responsible for protein production. The RNA core is stabilised by a protein scaffold.

RNA - Ribose nucleic acid (RNA) is similar to DNA. For a protein to be made from a gene a working copy of the gene is made from RNA. The RNA is read by the ribosome, which “translates” it into protein. Other RNA molecules are enzymes, performing chemical reactions.

RNA world - A proposed stage early in the evolution of life in which RNA acted as both genetic material and enzyme.

Telomerase - Telomerase makes the DNA ends of linear chromosomes. Telomerase is made up of an RNA portion and a protein portion, and probably dates back to the RNA world.

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