phenotype

Bacteria do not develop transmissible spongiform encephalopathies, but they have been found to produceÂ prions – proteins that can adopt alternative conformations withÂ different functions.

Prion diseases, aÂ frequent topicÂ on this blog, are caused by misfolding of a normal cellular prion protein (illustrated; image copyright ASM Press). Prion proteins are found in other organisms, where the alternative conformation confers a new, non-pathogenic function to the protein. At least 12 different prion proteins have been found in yeast, and they confer the ability to grow more efficiently under certain conditions. Now prions have been discovered in bacteria (link to article).

A search of 60,000 bacterial genomes for proteins with prion-forming domains revealed one in the transcription termination protein Rho from Clostridium botulinum (Cb-Rho). When produced in E. coli, the protein forms amyloid – protein aggregates in the form of fibrilsÂ – that areÂ characteristic of prions. A 68 amino acid stretch of Cb-Rho can functionallyÂ substitute for the prion-forming domain of a yeast prion-forming protein. This protein, called Sup35, can read stop codons in the prion state, and this phenotype was recapitulated in yeast by the Clostridium prion.

The Cb-Rho prion can convert between prion and non-prion conformations in E. coli. This property was demonstrated by placing a Rho-dependent terminator between a promoter and the lacZ gene, the product of which produces a blue color. In the prion state, Rho has decreased activity, leading toÂ blue cells. In the non-prion state, normal termination leads to pale blue colonies. A mixture of blue and pale blue colonies wasÂ observed, showing that Rho exists in the prion and non-prion states.

The prion conformation was also shown to be heritable. Blue colonies always gave rise to blue colonies, while pale blue colonies formed pale blue colonies. The blue colony color lasted for over 120 generations.

The finding of a prion in bacteria indicates that this form of protein-based heredity arose before eukaryotes emerged on Earth. Similar prion-like protein domains have also been found in other phyla of bacteria, suggesting the existence of an important source of epigenetic diversity that can allow bacterial growth underÂ diverse conditions. Exactly how bacterial prions confer new functions will be exciting to discover.

Last time we learned that eukaryotes probably didnâ€™t invent the nucleus. Now we find that prions likely emerged first in bacteria. Did eukaryotes invent anything?

To a molecular biologist, the word ‘evolution’ evokesÂ images of fossils, dusty rocks, and phylogenetic trees covering eons. The fields of molecular biology and evolutionary biology diverged during the twentieth century, butÂ new experimental technologies have lead to a fusion ofÂ the two disciplines. The result is that evolutionary biologistsÂ haveÂ theÂ unprecedented ability to evaluate how genetic change produces novel phenotypes that allow adaptation. It’s a greatÂ time to start a new podcast on evolution!

Molecular biology is an experimental approach that was born in 1953 with the discovery of the structure of DNA. Its goal is to understand how cells and organisms work at the level of biological moleculesÂ such asÂ DNA, RNA, and proteins. Some of the experimental tools of molecular biology include recombinant DNA, nucleotide sequencing, mutagenesis, and DNA-mediated transformation. The experiments of molecular biology often involve simplified, or reductionist systems in which much of the complexity of nature is ignored. Variation in individuals, populations, and the environment are set aside. Data produced by the techniques of molecular biology can lead to decisive conclusions about cause and effect.

Evolutionary biology embraces variation, and in fact attempts to explain it. The basis for variation in organisms is usually inferred by associating phenotypes, sequences, and alleles. The problem with this approach is that alternative explanations are often plausible, and conclusions are rarely as decisive as those achieved with molecular biology. We can turn to Darwin’s finches as a good illustration of the difference between fields. Darwin hypothesized that variation in theÂ beaks of finches was a consequence of diet,Â but how such variation occurred was unknown. It was not untilÂ 2004 that it was shown that beak shape and size could be controlled by two different genes.

The techniques of DNA sequencing, mutagenesis, and the ability to introduce altered DNA into cells and organisms have been the catalyst for the fusion of molecular biology and evolutionary biology into a new and far more powerful science, which Dean and Thornton call a ‘functional synthesis’. As a consequence, genotype can be definitively connected with phenotype, allowing resolution of fundamental questions in evolution that have been puzzles for many years.

Microbes are perfect subjects for study by evolutionary biologists, as they are readily manipulable and rapidly reproduce. However no organism is now very far from the eye of this new science. Subjects as diverse as insecticide resistance, coat color in mice, evolution of color vision, and much more are all amenable to scrutiny by the ‘functional synthesis’.

This Week in Evolution will cover all aspects of the functional synthesis, irrespective of organism. My co-host is Nels Elde, an evolutionary biologist at the University of Utah. Nels has appeared on This Week in VirologyÂ to discussÂ the evolution of virus-host conflict,Â andÂ his lab’s story on theÂ evolutionary battle for iron between mammalian transferrin and bacterial transferrin-binding protein was covered on This Week in Microbiology.

You can find This Week in Evolution at iTunesÂ andÂ at MicrobeTV.

Prions in bacteria

TWiEVO: This Week in Evolution