Tuesday, October 17, 2006

Smallest genome clocks in at 182 genes ("I predict that, if a form of life is ever discovered in another part of the universe ...")

Smallest genome clocks in at 182 genes, How much can you remove from a bacterium before it stops working?, News@Nature, 12 October 2006, Philip Ball

[Graphic: Carsonella ruddii, New Scientist]

Also at: Biology News, Livescience, NPR, Science, New Scientist and Scientific American. How small can a genome get and still run a living organism? Researchers now say that a symbiotic bacterium called Carsonella ruddii, which lives off sap-feeding insects, has taken the record for smallest genome with just 159,662 'letters' (or base pairs) of DNA and 182 protein-coding genes. At one-third the size of previously found 'minimal' organisms, it is smaller than researchers thought they would find. At the same time, a second group reports another bacterium, Buchnera aphidicola, also with a surprisingly small genome - at just over 400,000 base pairs of DNA it's little more than twice the size of C. ruddii's, but again smaller than anything seen previously. ... The discoveries, reported today in Science, suggest that only a remarkably small collection of molecular parts is needed to make up a viable life form. This is misleading in that "viable life form" usually means independently free-living (otherwise a man being kept alive by a heart-lung machine would be "a viable life form"!), and that is contradicted further down in the same article where it is conceded that these smallest-genome bacteria are parasites - they are each dependent on their host to supply them with gene products and therefore that part of their host's genome which they depend on to survive should be added to their minimum gene count.

And "159,662 'letters' (or base pairs) of DNA" consisting of "182 protein-coding genes" is not "small." As the late astrophysicist Fred Hoyle pointed out, the probability of the spontaneous assembly of even one of the shortest protein-coding genes, the 200 base-pair gene which codes for the protein histone-4, is "equal to 10-120" and "Even if one were given a random choice for every atom in every galaxy in the whole visible universe" (i.e. ~1080) "the probability of discovering histone-4 would still only be a minuscule ~10-40":

"Essentially, the same amino acid chain being found also in other animals and even in plants, we have a case in histone-4 where more than 200 base pairs are conserved across the whole of biology. The problem for the neo Darwinian theory is to explain how the one particular arrangement of base pairs came to be discovered in the first place. Evidently not by random processes, for with a chance 1/4 of choosing each of the correct base pairs at random, the probability of discovering a segment of 200 specific base pairs is 4-200, which is equal to 10-120. Even if one were given a random choice for every atom in every galaxy in the whole visible universe the probability of discovering histone-4 would still only be a minuscule ~10-40." (Hoyle, F., "Mathematics of Evolution," [1987], Acorn Enterprises: Memphis TN, 1999, pp.102-103).

It's rather as if a computer can be put together from just a handful of transistors. This is not a good example for a Darwinist to use. The problem with "a computer" is that, in its basic form, i.e. one that "can be put together from just a handful of transistors", it would be irreducibly complex in that it would not work half as well with the first half of the transistors-it would not work at all (as a computer-it would work as a door stop!) until all the transistors were assembled in the right order!

... But researchers warn that the natural streamlined bacteria are both symbionts, dependent on their host organisms for certain functions or nutrients that they can't provide themselves. "They can't be grown on their own," says Latorre. As I commented above, this contradicts the earlier claim that, "only a remarkably small collection of molecular parts is needed to make up a viable life form" (in the usual sense of independently living).

... Geneticist Craig Venter ... is hoping that small-genome organisms will point the way to a minimal genome: the smallest possible set of genetic parts needed to generate life, from which an organism might then be designed and built. One of Venter's goals is a synthetic bacterium that makes fuels such as hydrogen from renewable raw materials. When Venter announced plans to synthesize a working genome from scratch in 2002, his team estimated that one well-studied bacterium needed at least 300 or so of its genes to survive (see 'Venter aims for maximum impact with minimal genome'). But estimates have been getting smaller. In the New Scientist report on this it quotes Venter as dismissing C. ruddii as "irrelevant" and not saying "anything about the genes required for independent cell growth" (my emphasis):

"But Venter, who aims to build an artificial bacterium with as few genes as possible, says the use of the new findings is limited because C. ruddii is so dependent on its host. This makes it somewhat irrelevant to his team’s efforts to make self-sufficient bacteria. "I don’t think it says anything about the genes required for independent cell growth," says Venter."

A review published in Nature Molecular Systems Biology this year posited a hypothetical minimal genome of 113,000 base pairs and 151 genes - rather close to the new find. This NMSB paper is very interesting because it is about a Minimal Cell Project (MCP) and gives details of the enormous amount of intelligent design required to build "a minimal cell" and even then they are mostly using parts of existing E. coli cells-not building the first living cell from non-living chemicals as the `blind watchmaker' would have to do at the origin of life. Here are some quotes from that paper, with my emphasis:

"Life, like a machine, cannot be understood simply by studying it and its parts; it must also be put together from its parts":

"Synthesizing a minimal cell will advance knowledge of biological replication. ... The meaning of 'synthetic' (from Greek sunthesis, to put together) discussed here bypasses the current reliance of synthetic biology on cells or macromolecular cell products: the aim is to put together an organism from small molecules alone. ... Life, like a machine, cannot be understood simply by studying it and its parts; it must also be put together from its parts. Along the way to synthesizing a cell, we might discover new biochemical functions essential for replication, unsuspected macromolecular modifications or previously unrecognized patterns of coordinated expression." (Forster, A.C. & Church, G.M., "Towards synthesis of a minimal cell," Molecular Systems Biology, Vol. 2, 22 August 2006)

So what unintelligent:

"blind, unconscious, automatic process which ... has no purpose in mind. ... has no mind and no mind's eye. ... does not plan for the future. ... has no vision, no foresight, no sight at all. ... is the blind watchmaker" (Dawkins, R., "The Blind Watchmaker," 1986, p.5).

could, or would: 1) first produce all the "parts" of "a machine"; and then 2) "also ... put together from its parts" that "machine"?

"The only cellular alternative is a perturbed natural cell, an incredibly complex system even for the simplest of cells" (so how did a `blind watchmaker' build the first "incredibly complex system ... for the simplest of cells"?):

"How good a model would an artificial, protein-based, minimal cell be for natural cells? The only cellular alternative is a perturbed natural cell, an incredibly complex system even for the simplest of cells. A much simpler purified system based on a real cell would thus be easier to model and understand. It could certainly answer questions that cannot be answered in vivo or in crude extracts, such as which macromolecules and macromolecular modifications are sufficient for subsystem function. However, even the simplest minimal cell would still be highly complex; so its construction and study would be facilitated by substituting some of the necessary subsystems with simpler analogs. Should the simpler in vitro model turn out to be a poor model for the more complex in vivo system, one could always construct a more complex in vitro system that may better reflect in vivo." (Forster & Church, Ibid., 2006).

"Like any engineering project, this requires detailed blueprints, raw synthetic capabilities and an overall diagnostic and debugging strategy" (again, how would a `blind watchmaker' comprised of non-living chemicals - by definition for the origin of the first living cell-come up with the equivalent of an "engineering project" which "requires detailed blueprints" and "an overall diagnostic and debugging strategy"?):

"The ideal approach for synthesizing a cell would allow all of the machine parts to be understood and tested. Like any engineering project, this requires detailed blueprints, raw synthetic capabilities and an overall diagnostic and debugging strategy. ... What is needed is some way of defining a near-minimal genome and then a strategy that will lead inexorably to an understanding of all of its parts." (Forster & Church, Ibid., 2006)

"Theoretical and experimental studies have attempted to establish a minimal set of genes needed for a self-replicating system in a cushy constant environment of unlimited, small molecule nutrients" (so how did a `blind watchmaker' do it on the early Earth where there was no artificial, air-conditioned lab, with a "cushy constant environment of unlimited, small molecule nutrients"?):

"Theoretical and experimental studies have attempted to establish a minimal set of genes needed for a self-replicating system in a cushy constant environment of unlimited, small molecule nutrients. Three basic approaches present themselves. ... Comparative genomics ... searches for genes that have homologs in the genomes of groups of organisms. The approach estimates from 50 to 380 genes in a minimal genome .... Genetics ... searches for essential genes by mutating one gene at a time. This approach estimates 430 genes in a minimal genome (out of Mycoplasma genitalium's total of 528 ... Biochemistry ... identifies from cell fractions those gene products essential for the reconstitution of biochemical reactions. It does not suffer from the above problems ... However, the cellular subsystems must be integrated and thoroughly tested for accuracy on long templates before they can be considered physiological. ... Mindful of the remaining self-replication functions that need to be discovered ... it seems likely that a largely biochemical approach, now further empowered by mass spectrometry analyses and genetic and comparative genomic information, will be the most practical route to define a near-minimal, well-understood genome." (Forster & Church, Ibid., 2006)

I predict that if scientists ever do manage to build this minimal, self-replicating, living cell (which I doubt -but do not rule out-that they ever will), they will find that it needs a lot more than 151 genes, and nearer (if not more than) 1,500 genes because: 1) "all microbial genomes that fall below 1,500 belong to parasites":

"One way to explore the minimum complexity of independent life is to survey the microbial database for the smallest genome. ... to exist independently, life requires a minimum genome size of about 1,500 to 1,900 gene products. (A gene product refers to proteins and functional RNAs, such as ribosomal and transfer RNA.) The late evolutionary biologist Colin Patterson acknowledges the 1,700 genes of Methanococcus are `perhaps close to the minimum necessary for independent life.' [Patterson, C., "Evolution," Comstock: Ithaca NY, Second edition, 1999, p.23] ... So far, as scientists have continued their sequencing efforts, all microbial genomes that fall below 1,500 belong to parasites. Organisms capable of permanent independent existence require more gene products. ... Some 1,500 different gene products would seem the bare minimum to sustain this level of metabolic activity. .... The discovery of parasitic microbes with reduced genome sizes, like Mycoplasma genitalium ... with 470 ... gene products, respectively ... indicates that life exists, though not independently, with genome sizes made up of smaller than 1,500 genes. These microbes are not good model organisms for Earth's first life forms because they cannot exist independently. .... Scientists... have used the M. genitalium and H. influenzae genomes to estimate the minimum gene set needed for independent life. .... This approach indicated that a set of 256 genes represents the lower limit on genome size needed for life to operate. Using a similar approach, an international team produced a slightly lower minimum estimate of 246. .... In addition to theoretical estimates, researchers have also attempted to make experimental measurements of the minimum number of genes necessary for life. .... One experiment performed on the bacterium Bacillus subtilise estimated the minimal gene set numbers between 254 and 450. A similar study with M. genitalium determined the minimum number of genes to fall between 265 and 350. Random mutations of the H. influenzae genome indicate that 478 genes are required for life in its bare minimal form. The genome of the extreme parasite Buchnera ... varies, with the smallest estimated to contain 396 gene products. Theoretical and experimental studies designed to discover the bare , minimum number of gene products necessary for life all show significant agreement. Life seems to require between 250 and 350 different proteins to carry out its most basic operations. That this bare form of life cannot survive long without a source of sugars, nucleotides, amino acids, and fatty acids is worth noting." (Rana, F.R. & Ross, H.N., "Origins of Life: Biblical And Evolutionary Models Face Off," Navpress: Colorado Springs CO, 2004 pp.161-163).

yet 2) there would be constant selection pressure for some independently living bacteria to occupy their minimal genome ecological niche for (since a larger genome carries a higher energy cost than a smaller genome).

So this is strong (if not conclusive) evidence that "Organisms capable of permanent independent existence require" about "1,500 different gene products" which "would seem the bare minimum to sustain this level of metabolic activity." And again remember Hoyle's point above that unintelligent `blind watchmaker' processes cannot plausibly assemble even one of the shortest genes!

It is generally thought that a minimal genome will need to include genes for replication and for protein synthesis, and probably also for making the enzymes needed to construct basic building blocks, such as amino acids, from chemicals available in the immediate environment. ... Note this is for a "minimal genome" and therefore for the first genome. That is, the origin of life had to make a single-step jump from non-living chemicals to a living self-replicating cell with "a minimal genome" which needed "to include genes for replication and for protein synthesis ... for making the enzymes needed to construct basic building blocks, such as amino acids, from chemicals available in the immediate environment"!

Therefore, to paraphrase Richard Dawkins ("The Blind Watchmaker," 1986, p.288):

"`I predict that, if a form of life is ever discovered in another part of the universe ... it will be found to resemble life on Earth in one key respect: it will have' been created by an Intelligent Designer!

Stephen E. Jones, BSc (Biol).
Genesis 6:8-10. 8But Noah found favor in the eyes of the LORD. 9This is the account of Noah. Noah was a righteous man, blameless among the people of his time, and he walked with God. 10Noah had three sons: Shem, Ham and Japheth.

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