"The chemist puts his mind at rest regarding the existence of life, just as the physicist calms his regarding the existence of matter, simply by turning his back on the problem. Thereby he suffers nothing in his practical task as a man of science01."
Lunar Albedo nearside
Lunar Albedo farside
|Source: U.S. Navy Clementine
Early Earth Landscape
Credit: Artwork copyright 2006 Don Dixon/cosmographica.com
components of the central dogma are as follows:
• DNA and RNA molecules record and process the genetic information in all living species. The molecules consist of a backbone built up of sugars with the genetic information attached to the backbone. The first understanding of the genetic role of DNA and RNA was discovered in the 1940s. Watson and Crick first described the structure of these molecules in 1953.
• All genetic information is recorded in digital form. Every living species does this in the same way.
+ The basic information is recorded as one of four specific molecules called nucleotides. They are designated A (adenine), C (cytosine), G (guanine), and T (thymine). In DNA, the nucleotides always appear as base pairs: A pairs with T, and G pairs with C. In RNA, T is replaced by U (uracil) (see Figure 3). The structure of the nucleotides and the DNA backbone are modeled and described here.
+ A codon is a triplet of nucleotides recorded in successive positions in the DNA.
+ A gene is a sequence of codons that code for a protein. Special start and stop codons mark the beginning and end of the gene13.
* The DNA molecule is a long sequence of nucleotide base pairs attached to a double-helix backbone. The pairs are placed in the DNA like rungs in a ladder with two long right-handed spirals forming the sides. In the pairs, the nucleotides on the right (in the direction of transcription) define the gene codons.
* The DNA molecule codons specify for amino acids which are the building blocks of proteins.
There are about 20 amino acids used in all living species, and all are left-handed (with rare exceptions). This is somewhat unexpected since natural (inorganic) processes produce left- and right-handed amino acids in equal numbers. Since it appears that life based on right-handed amino acids would work just as well, this seems to be another example of contingency, and again argues for a single original creation of life on earth.
* Each codon corresponds indirectly to an amino acids that will be used to form proteins as described below. The correspondence is summarized in a table (figure 5) which is part of the central dogma. All living species incorporate this table (with a very few species using minor variations) which appears to be quite contingent in Gould's sense of the word. There does not appear to be any deterministic or chemical basis for these particular associations between nucleotide triplets and the selected amino acids. Therefore one would assume that an independent generation of life would develop a different codon table, even if it would come up with a similar coding scheme for genetic information. This is a strong argument for the conclusion that all life on earth arose from a single life-forming event.
* Special molecules associate each codon used in the DNA to an amino acid. These are the transfer RNA, t-RNA, further described below. Genes to produce these t-RNA molecules must be part of the genetic code recorded in the DNA. Thus the codon table is built into the DNA and is the same for all species of life.
* Complex linear motor molecules called RNA polymerases read the DNA codons for a gene, and form a messenger RNA molecule, m-RNA. This process is called transcription.
* The m-RNA molecule then moves away from the DNA and attaches to another complex molecule, the ribosome, which controls the codon translation. This is another linear motor molecule.
The ribosome is in itself an exceedingly complex compound molecule consisting of an upper and a lower part. The ribosome is the place where the codons of the m-RNA are translated into a sequence of amino acids and form a protein chain. Each codon is processed by the ribosome and adds a single amino acid to the protein chain.
The general function of the ribosomes is the same across all species, although the specific ribosome configuration varies somewhat. For an interesting description of how ribosomes work, see The Smartest Living Nanomachine. Here is one quote from the article:
"Ribosomes are found in practically identical form in every living cell on Earth, whether it be the single-celled archaea in the thermal vents of the ocean floor, the bacteria on the surface of the planet, or the cells in the human body. ... ribosomes are believed to be among the most-ancient molecular machines of life13.1."
A cell builds ribosomes from Ribosomal DNA genes. In Eukaryotes (proper cells), the nucleolus is the building site. About 150 genes are involved in the construction of ribosomes. A typical ribosome contains about 250,000 atoms. Of course ribosomes have to be constructed without the benefit of ribosomes (used to construct most other molecules in a cell). This requires additional genes, many of which do not appear in the final product. A typical cell has thousands of ribosomes.
* Translation in the ribosome requires the presence of transfer RNA molecules, t-RNA, designed for each amino acid. One end of the t-RNA has a codon from the codon table, the opposite end has the corresponding amino acid attached. The ribosome reads the codons on the m-RNA one at a time, matches the codon to a corresponding t-RNA molecule, detaches the amino acid from the t-RNA, and adds it to a building chain of amino acids that will form a protein when the chain is complete. The t-RNA molecules are released to capture another amino acid for future use.
t-RNA molecules are small -- about 74-95 nucleotides. A cell requires a minimum of 31 t-RNA types to translate all of the 64 possible codons. The lower number is possible because many codon translations are in effect defined by only 2 nucleotides: for example, from the codon table above it is evident that CUx is the amino acid leucine, regardless of which nucleotide is in the x position14.
* On completion of a protein chain, the protein folds into its final form. There is some mystery (see, for example, the waffling in the Wikipedia article) as to how this is done, since the specific folding can be critical. In general a given protein chain could be folded in many ways, but without proper folding, which occurs after the entire protein chain has been completed, the protein will not function properly.
Associated to the question of folding is the Levinthal paradox, which asserts that the "best" protein folding cannot come from any process of sampling even a small fraction of the possible folding configurations, because such an approach would be far too slow.
"Computational approaches to protein structure prediction have sought to identify and simulate the mechanism of protein folding, however these have been largely unsuccessful." -- Wikipedia.
* Gene expression depends critically on gene regulation: the methods used to determine when (or if) specific genes are to be read. Hovering over the entire information content of the DNA is an entire separate layer of this regulatory information, involving many specialized molecules and procedures to control gene blocking and gene expression.
For example, in higher species, development genes determine how an embryo evolves from the initial fertilized egg to maturity. Incorrect sequencing of events here is a recipe for disaster. Even the simplest single-celled species must follow specific sequential gene expression. To put it simply, not every gene can be expressed all the time, as rapidly as possible. There must be some imposed order provided by a mechanism for gene regulation.
In the view of some, the complexity and information content involved in gene regulation (particularly in eukaryotes) is potentially greater than the information content of the DNA itself.
Even the Simplest Life on Earth is Vastly Complex
NO known natural procedure can produce such complexity.
Every species of life has the full machinery of the Central Dogma. It seems impossible to imagine how any form of self-sustaining life could exist without the whole of this complex, inter-connected machinery already in place.
The problem of how the Central Dogma could be created by purely natural processes, seems as insoluble as the question of how the density and smoothness of the primordial universe came to have its precise and essential values just after the cosmic expansion (see Chapter 3). So both the universe and life begin with apparently insoluble issues for evolution by purely natural means.
Undoubtedly future research will show how isolated parts of the vast enterprise can be achieved naturally: for example, there may be experimental verification that a reduced codon table suffices to specify for protein amino acids in a viable life form, or that a simplified method of peptide synthesis exists. But there are two paradoxes that stand in the way of any comprehensive natural solution to this complexity. These are called Eigen's Paradox and Levinthal's Paradox. Eigen's paradox states, in effect, that functional protein changes over 100 amino acids in length cannot be produced by random natural processes. Levinthau's paradox states that complex protein folding cannot be arrived at by natural processes 17.
One can reasonably conclude that if the vast complexity of the genetic processes had been known in Darwin's day, any attempts to extend his theory to the origin of life by purely natural processes would never have been taken seriously.
One of the amazing facts discovered in the past few decades is the extent to which a living cell uses molecular motors and other complex molecules to do even the most basic tasks.
ATP synthase. We mention ATPase first because this is a molecular motor that is used throughout the implementation of the Central Dogma, and so, to that extent, it is even more basic to all living species than the Central Dogma itself! The next chapter has further remarks on the ways that a cell uses the energy "battery", ATP.
ATP synthase (Figure 8) is a rotary motor that is powered by protons (H+) rather than electrons as in modern electric motors.
The proton flow arises because the atp synthase is embedded in a membrane which is more acidic on one side than the other. A number of genes (typically 8, labeled "a" to "h") specify the various parts of the synthase: for example, M. genitalium, a parasitic bacterium with one of the smallest known genomes. Its DNA includes the eight ATPase genes designated atpA through atpH. The motor is very complex, and appears to be universal (see the box)18.
The following molecular motors are found in all species because they are required to carry out the Central Dogma:
RNA Polymerase (RNApase). The formation of m-RNA implies the presence of a linear motor (RNA polymerase (RNAPase)) that moves along the DNA. It moves to a base pair, separates the pair, retrieves a matching nucleotide from the surrounding medium, attaches it to the m-RNA chain, and then re-connects the DNA pair as it advances ahead one base pair.
Unlike ATPase and the ATP molecule itself, the RNA polymerase that transcribes DNA has a variety of forms in a cell and varies considerably over the domain of living species. However all function as linear motors, and their functions are correspondingly complex. Life cannot exist without these complex motor molecules.
One curious fact is that archaea, the domain of bacteria that includes the so-called extremophiles as well as many autotrophs, has an RNAPase that is closer to that of eukaryotes, living species that are much more advanced than bacteria. This poses a problem of classification because the archaea are generally thought to be more ancient than bacteria (as the name implies), but their RNAPase appears to be more advanced. We will return to this at the appropriate point in the following chapters.
In advanced species the RNAPase uses a number of "add-on" auxiliary molecules that perform a number of functions such as transcription error checking and correction. As remarked in the Wikipedia article, "the activity of [RNAPase] is both long and complex and highly regulated."
In a typical transcription, multiple copies of RNAPase operate simultaneously on a single DNA gene, as shown in Figure 9, viewed on a scanning electron microscope.
Ribosome. The translation of m-RNA to form a protein implies another linear motor (the ribosome). It attaches to the m-RNA, reading it one codon at a time, matches that codon to the appropriate t-RNA, detaches the amino acid from the t-RNA, adds it to the growing protein chain, releases the t-RNA and then advances along the m-RNA to the next codon.t-RNA Synthases. The t-RNA loads itself with the proper amino acid using the assistance of another molecule (t-RNA synthetase -- a separate synthetase exists for most distinct codons), and then cooperates with the ribosome to release the amino acid. Some authors describe the t-RNA as a motor molecule in its own right because of the way it changes configuration as it gains entry into the ribosome.
We noted above the complexity of the ribosomes. Many genes are encoded in the DNA to form the ribosome, which has a large upper part and a smaller lower part. In M. genitalium, mentioned above, the genome includes about 33 genes to form the upper part, and about 20 genes to form the lower part.
DNA duplication. Duplication of the DNA is an essential part of cell reproduction. There are two different ways that this is done -- all living species have to use one or the other: DNA polymerase or DNA reverse transcriptase. These are also linear motor molecules similar to RNA polymerase.
Production of Sugars in the DNA backbone. This will be discussed in the next chapter. This process includes the molecule RuBisCO (see footnote 9) which appears to be necessary to fix carbon from atmospheric CO2.
“I must confess that I was at first startled and alarmed by rumours of changes and discoveries which, I was told, were to overturn at once the science of geology as hitherto received, and all the evidences which had been drawn from it in favour of revealed religion. Though well persuaded that at all times, and by the most unexpected methods, the Most High is able to assert Himself, the proneness of man to make use of every unoccupied position in order to maintain his independence of his Maker seemed about to gain new vigour by acquiring a fresh vantage-ground. The old cry of the eternity of matter, and the 'all things remain as they were from the beginning until now,' rung in my ears. God with us, in the world of science henceforth to be no more! The very evidences of His being seemed about to be removed into a more distant and dimmer region, and a dreary swamp of infidelity spread onwards and backwards throughout the past eternity.”
She argued that there was an attempt to remove inconvenient facts into a "distant and dimmer region" so that an atheistic (or at least Creator-less) agenda could advance without impediment. The facts are still there, but are pushed away, out of view. Biologists who believe in evolutionary change by purely natural processes (i.e. without a divine Creator) may be vulnerable to this charge regarding the origin of life. Their a-priori assumptions conflict with the observed data, so the data must be removed from view. This is the opposite of what Johannes Kepler did when his data on the movements of the planet Mars conflicted with theory -- see the Box on Kepler.
|The Sleepwalkers (1959) stated: "For the first time since antiquity, an attempt was made not only to describe heavenly motions in geometrical terms, but to assign them a physical cause." (p. 258). These laws came about because Kepler realized that the astronomical model predictions of Ptolemy and Copernicus "were only accurate within a margin of ten minutes" (p. 322) when compared with Tycho Brahe's precisely measured observations of the planet Mars, accurate to about 1 minute. Earlier astronomers such as Copernicus and Ptolemy would have "corrected" the geometry by adding epiycles, but Kepler concluded that the assumed orbital model was wrong, and sought to correct the model. His success marked the start of modern science.|
(quoted in Koestler's book, p. 322) described the essence modern
science: "All the world over and at all times there have been practical
men, absorbed in 'irreducible and stubborn facts': philosophic
temperaments who have been absorbed in the weaving of general
principles. It is this union of passionate interest in the detailed
facts with equal devotion to abstract generalization which forms the
novelty in our present society." The novelty is not that scientists
sought generalizations (such as that planets move at constant speed
over circular orbits, with superimposed epicycles) but that the
generalizations must relate to a physical cause that must agree in
detail with observed facts.
online. The purpose of the symposium was to estimate the smallest
possible size for a self-sufficient microorganism. The question arose
to address whether the "Martian fossils" discovered in the early 1990s
might be the remains of a living microorganism. The symposium concluded
that these "fossils" were too small to contain the minimum number of
molecules required to carry out life processes of any conceivable kind
of living organism.
|Sizes of Existing Species. Figure
?? compares the DNA size of species today. Note that the
genome size only weakly correlates with the complexity of the species:
for example, the dna of humans is only of middling size when compared
with other mammals, and many plants have dna that is orders of
magnitude larger than the human dna.
Viruses have the smallest genomes, but since viruses cannot carry out the essential cell functions of metabolism and reproduction, they cannot carry out the necessary tasks of life without co-opting the dna of bacteria; thus if "living" means the ability to engage in these functions, viruses do not qualify as "alive." The smallest viral DNA has about 3,200 base pairs [Spherical hepatitis B Virus (HBV)], coding for four genes.
The smallest DNA sizes of the kingdoms are (from this Figure):
• Bacteria DNA are over 400,000 base pairs (bp);
• Fungi DNA are over 10,000,000 bp;
• Plant DNA are over 65,000,000 bp; and
• Animal DNA are over 400,000,000 bp
Still the question arises: how small could the DNA of a living species possibly be, and still be able to metabolize and reproduce? Perhaps all species today are much larger than the minimum size possible.
This very question was the topic of a 1998 symposium conducted by the National Research Council of the National Academy of Sciences. The proceedings are published in the symposium Proceedings, Size Limits of Very Small Microorganisms, published in September, 1999. Invited participants included J. William Schopf, author of Cradle of Life, who will figure prominently in the next chapter.
A major factor that led to this symposium was the alleged discovery of Mars fossils in meteorites retrieved from Antartica and announced in 1996 by NASA scientists. A number of scientists, Schopf in particular, questioned whether they were genuine fossils, and the resulting controversy within the scientific community was a factor leading to this symposium. The question was not whether there could be remnants of life on Mars, but whether these particular specimens could possibly be fossils (whatever their origin). Schopf contended that the "fossils" were too small to contain enough biological material to support a living cell. He argued that the fossils were about 1000x too small to support any kind of life and therefore they were artifacts of the meteorites and not fossils at all.
The symposium cited "the recent report of evidence for life in a martian meteorite" as it posed the question (citing the Summary), "How small can a free-living organism be?" They sought an answer based on a "a fundamental understanding of the chemistry and ecology of cellular life." The concensus of the symposium was that "Free-living organisms require a minimum of 250 to 450 proteins along with the genes and ribosomes necessary for their synthesis. A sphere capable of holding this minimal molecular complement would be 250 to 300 nm in diameter." This is far larger than the alleged Martian fossils.
A statement of the minimum genome size varies among the participants. One participant suggested 320,000 bp coding for 256 proteins (p.43), but without asserting that this size could be free-living. A "cell that synthesizes all of its cellular material from CO2 [an autotroph, which the first life must be -- dcb] requires... closer to 750 genes." For comparison the symposium estimated that the smallest actual modern autotroph has about 1500 genes. [pp 77-78]. Using 1000 bp as the size of an average gene, the minumum genome size for an autotroph must be at least 750,000 bp.
The symposium noted that the bacterium Mycoplasma genitalium, one of the smallest living species on earth, is (at 582,970 bp) close to the limit of smallest possible size, but that this bacterium is not fully self-sufficient because it depends on the availability of organic food and enzymes provided by its host, which a fully self-sufficient organism would have to manufacture. In 2002, a smaller bacterium was discovered, but it too is incapable of independent existence.
Among modern bacteria on earth, the smallest autotroph -- able to manufacture all of its own food and enzymes from inorganic sources -- requires over 1 million bp. Such a bacterium must include DNA coding to manufacture the nucleotides and amino acids, because these buildingblocks of life do not occur naturally in significant amounts. Even this size assumes the availability of fixed nitrogen.