A Brief Bit More on Reductive Evolution in M. leprae

In a previous post I discussed the evidence for reductive evolution in Mycobacterium leprae, an interesting obligate intracellular parasite.




At the 2008 ASM General Meeting, the Division U keynote lecture was headed by Tom Gillis of the National Hansen's Disease Program. His talk described the same work I cited in the previous article, which showed the immense amount of pseudogenes in the M. leprae genome.

Gillis was interested in elucidating the role of these pseudogenes. This included asking whether or not these genes are transcribed and translated. If these pseudogenes are not providing any function, then it stems that the cells will not put energy towards their expression.

The work he discussed showed that ~44% of all M. leprae transcription was due to pseudogene expression. There doesn't appear to be a locational bias for pseudogene transcription either. Looking closely at 10 pseudogenes downstream of full-length genes, only 8 produced full-length transcripts.

More indepth in silico analysis shows that all these pseudogenes are unilogs (no duplicates present in the M. leprae genome), the vast majority lack a strong Shine-Delgarno sequence upstream, ~75% lack a translational start codon, and ~98% have one or more in-frame stop codons inserted.

This indicates that a very small percentage of pseudogene transcripts actually create a full-length translational product. So, although the cells still create the transcript, few (if any) resources are put towards creating a functional (or detrimental) protein product.

I also picked up some interesting epidemiological facts of the M. leprae genome. For one, the global M. leprae population is nearly clonal (1 polymorphism to 20,000bp compared to 1:5000 for M. tb.). However, variation in SNPs can be seen in local populations. In looking at ~60 cases from a town in India, the bug had a higher rate of diversity than compared to 3 cases in the South Eastern US or to 20 wild armadillos. Furthermore, the US cases and the wild armadillo cases were strikingly similar on an SNP scale.

I think an important point to take home from this is that M. leprae is still an evolving organism, and we are only catching a snapshot in time. It is a prime example of a parasite that has come to depend greatly on its host and has lost the ability to function outside said host.

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Other articles of mine that may be of interest
Reductive Evolution in Mycobacterium Leprae
Evolution of Phage Capsid and Genome Size (Another 2008 ASM General Meeting Lecture)

Evolution of Phage Capsid and Genome Size

Viruses come in all shapes and sizes. From the very small, such as the picornaviruses or the parvoviruses, to the very large like mimivirus, or the herpesviruses, and poxviruses. These large viruses are not just large in physical size, but in the size of their genomes as well.

At the recent 2008 ASM General Meeting, Roger Hendrix of the University of Pittsburgh, laid forth a rather interesting hypothesis as to how large genomes, and the capsids that hold them came into existance and how they managed to be competitive in the gene pool.

Using phage P1 as an example, we know that larger capsids can be created "simply" by a single mutation allowing capsid subunits (capsomers) to come together in a quasi-equivilant matrix that is larger than the previous. This matrix follows the mathematical model set by Casper and Klug, and has discrete sizes (triangulation numbers, such as T=1,3,4,7,13). An increase in T number, as in our P1 example, causes a dramatic increase in capsid volume. Hendrix proposes that a mutation causing a such a shift acts as an evolutionary ratchet, and therefore smaller capsid sizers would no longer be available.

Now that we have a larger capsid, the phage now has the ability to package much more DNA. Not only does it have the ability, but in many cases, the phage MUST package DNA until its capsid is filled (headfull-packaging). With a larger capsid, phages who package via headful mechanisms now must package more DNA creating a greater amount of redundancy in its genome.

Hendrix explained that a greater amount of terminal redundancy leads to greater resistance from DNA damaging agents, specifically UV light. Although some in the session contended this, Hendrix described large amounts of genomic redundancy as an evolutionary advantageous trait for phages which live on the surface of the ocean and soil.

Furthermore, the extra space in the genome acts as a virtual genetic laboratory to aquire and mutate genes without disrupting the ability of the phage to survive. Gene aquisitions and subsequent mutations could create genes which provide some sort of marginal (or large) benefit to the phage or the host it infects.

With a simple click of the ratchet and a headfull of DNA, the role that large phages play in novel gene development are only now beginning to become clear.

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My posts on similar topics

Mosaicism: Life on a Small, Ever Changing Scale

The Definition of Life; and, Taxonomy as We Know It