December 29, 2009 | David F. Coppedge

Simplest Microbes More Complex than Thought

The smallest, simplest cells are prokaryotes.  These are the bacteria and archaea that lack a nucleus and are usually considered primitive.  Scientists are finding, though, that they know many of the same tricks as the more complex nucleus-bearing eukaryotes.
    PhysOrg reported that a species of Mycoplasma, among the smallest independent-living bacteria, is more complex than thought:

Even the simplest cell appears to be far more complex than researchers had imagined.  In a series of three articles in the journal Science, researchers including Vera van Noort at the European Molecular Biology Laboratory (EMBL) in Heidelberg, have provided a complete picture of a single cell for the first time.  The study has provided important new insights for bacterial biology.  For instance, prokaryotes – cellular organisms without a cell nucleus – seem to be more similar to eukaryotes than was previously thought.

Among the discoveries is that “The bacteria appeared to be assembled in a far more complex way than had been thought.”  Many molecules were found to have multiple functions: for instance, some enzymes could catalyze unrelated reactions, and some proteins were involved in multiple protein complexes.  Another surprise: “What is remarkable is that the regulation of the transcriptome – the collection of RNA that deals with copying genetic information stored in the DNA – appeared to be far more similar to that of eukaryotes than had previously been thought.”  Additionally, “Another surprising result of the research is that, despite its very small genome, the bacterium is extremely flexible: it adapts its metabolism to major changes in its environment,” the article said.  “It can therefore rapidly adapt to the available food sources and stress factors, just like the more complex eukaryotes.”
    One of the papers in Science to which PhysOrg referred said that some 200 molecular machines are found in this little microbe.1  At least 90% of the proteins in the proteome are involved in at least one protein complex.  “The study allows estimation of unanticipated proteome complexity for an apparently minimal organism that could not be directly inferred from its genome composition and organization or from extensive transcriptional analysis,” the authors said.  The microbe has one of the smallest genomes for any free-living cell, “making it an ideal model organism for the investigation of absolute essentiality.”  How many genes is that?  Answer: 689.  But many of the protein products are multifunctional.  They act like modular players in larger hierarchical complexes.  “Our analysis captured distinct mechanisms for multifunctionality that imply the combinatorial use of gene products in different contexts, for different functions,” they said.
    The other two papers in the series echoed these responses.  One studying the impact on genome reduction said,2 “Despite its apparent simplicity, we have shown that M. pneumoniae shows metabolic responses and adaptation similar to more complex bacteria, providing hints that other, unknown regulatory mechanisms might exist.”  The third paper said,3 “The surprisingly frequent expression heterogeneity within operons, the change of operon structures leading to alternative transcripts in response to environmental perturbations, and the frequency of antisense RNA, which might explain some of these expression changes, suggest that transcriptional regulation in bacteria resemble that of eukaryotes more than previously thought.
    An article in Science Daily focused on one functional particular trick in a bacterium.  A molecular chaperone named HdeA, which helps protect E. coli from stomach acid, invokes a “unique timed-release mechanism” to keep its proteins from clumping together.  It works, furthermore, by extracting energy from its environment, like a windmill or waterwheel. 

1.  Kuhner, van Noort et al, “Proteome Organization in a Genome-Reduced Bacterium,” Science, 27 November 2009: Vol. 326. no. 5957, pp. 1235-1240, DOI: 10.1126/science.1176343.
2.  Yus, Maier et al, “Impact of Genome Reduction on Bacterial Metabolism and Its Regulation,” Science, 27 November 2009: Vol. 326. no. 5957, pp. 1263-1268, DOI: 10.1126/science.1177263.
3.  Guell, van Noort et al, “Transcriptome Complexity in a Genome-Reduced Bacterium,” Science, 27 November 2009: Vol. 326. no. 5957, pp. 1268-1271, DOI: 10.1126/science.1176951.

Remember – all this complexity exists in one of the simplest organisms known.  It retains only what is essential for life and yet has 200 molecular machines, 689 genes, and a number of strategies for combining its gene products into numerous protein complexes that have multiple functions and are able to operate in sequence.  Most likely this organism has a stripped-down proteome for its parasitic lifestyle.  It probably began, therefore, as an even more complex organism – it is not evolving upward from a simpler form of life.
    Notice how often the researchers were surprised.  They found more complexity “than previously thought.”  Why?  Because they were thinking like Darwin.  They expected primitive simplicity, but they found higher levels of order and regulation than they expected.  689 genes is a lot of genes – even if each one were to produce only one protein.  But now we see that many of these genes produce multiple alternate transcripts, some of the transcripts act as regulators, and the protein products carry on multiple functions – many of them associating in diverse ways with other proteins in multiple complexes.  The words multifunction and multifunctional appeared numerous times in the papers.
    Our online book shows that it is inconceivably improbable for even one functional protein to form by chance.  Getting a second one to match the first is even harder.  Imagine getting all 689 by chance!  It militates so hard against evolution, it makes the word overkill sound wimpy.  This improbability calculated in 1972 has been reinforced strongly in the more recent book by Stephen Meyer, Signature in the Cell (06/27/2009 Resource of the Week).  We have known this fact for a long time.  There were calculations like this in the 1960s.  We are now approaching the year 2010.  It’s high time we jettison the useless Darwinian baggage that assumes these things will emerge by unguided processes, and return to looking at life as designed.  That’s the only way the observed complexity makes sense.

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