Is Folding Influenced by Nearest-Neighbor Gene Products?

Question: On a given stretch of chromosome in which DNA encodes for proteins A, B, and C (in that order), do proteins A and C aid (directly or indirectly) in the folding of B?

Note to self: This is something that could perhaps be tested in silico. Investigate folding of B in MD simulation, with/without gene products A and C present.

Nucleomorphs and Lateral Gene Transfer

Sharing of DNA between and across species, genus, family, and other lines can happen in many ways. I'm reminded of this by a forthcoming PNAS paper (Lane et al., below) that characterizes the genome of a nucleomorph found in the cryptophyte Hemiselmis andersenii. Nucleomorphs are small DNA-containing nuclei found in the plastids of certain cryptomonads (flagellated unicellular plants). They are thought to represent the remnants of ancient endosymbionts.

The authors of the PNAS paper explain: "The nucleomorphs of cryptophytes and chlorarachniophytes are derived from red and green algal endosymbionts, respectively, and represent a stunning example of convergent evolution: their genomes have independently been reduced and compacted to under one megabase pairs (Mbp) in size." The authors found that the two nucleomorph genomes they studied encoded no introns. Moreover, proteins encoded by nucleomorph DNA "are significantly smaller than those in their free-living algal ancestors."

I think a larger point that bears remembering here is that unicellular plants have no business having flagella in the first place. Not to put too fine a point on it, but: The existence of something like Hemiselmis andersenii is not easily explained in evolutionary terms without invoking a theory of lateral gene transfer.

Lane et al., "Nucleomorph genome of Hemiselmis andersenii reveals complete intron loss and compaction as a driver of protein structure and function" in PNAS, December 6, 2007, 10.1073/pnas.0707419104.

Another Example of Extreme Gene Transfer?

The only reason I have a question mark at the end of the title above is that the following study was not a genetic analysis but a protein-based analysis. Nevertheless it is suggestive of wholesale gene transfer having occurred between a retrovirus and mouse mitochondrial DNA.

Hayashida et al., "An integrase of endogenous retrovirus is involved in maternal mitochondrial DNA inheritance of the mouse" in Biochemical and Biophysical Research Communications (article in press), doi:10.1016/j.bbrc.2007.11.127.

Extreme Gene Transfer: How Widespread?

A theme I've been developing (clumsily) in recent blogs is that in the real world, DNA is shared between organisms, particularly microorganisms, across species lines (maybe genus, family, and other boundaries as well), rather more frequently than most people are prepared to believe.

Note to self: How would one determine how much free DNA (extracellular, non-viral DNA) is present in a gram of topsoil? Or a milliliter of benthic mud?

Hypothesis: Promiscuous, freeform DNA-sharing is a default behavior of (nearly all) microorganisms. The cell wall is a specialized organelle that exists to rate-limit this process.

Why make such a hypothesis? Two reasons:

1. Because it explains speciation (in microorganisms, at least) better than point-mutation trial-and-error.

2. Because it explains certain novelties of nature that are hard to explain otherwise, such as the recent finding of an entire bacterial genome incorporated in the genome of Drosophila. See: Dunning-Hotopp, Clark, Oliveira, Foster, Fischer, Torres, Giebel, Kumar, Ishmael, Wang, Ingram, Nene, Shepard, Tomkins, Richards, Spiro, Ghedin, Slatko, Tettelin & Werren, "Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes" in Science doi:10.1126/science.1142490.

Autism: Autoimmunity to hsp90?

Today, a study published in Pediatrics confirms that autistic children experience an attenuation of characteristic symptoms (specifically: irritability, hyperactivity, stereotypy, and inappropriate speech) during periods of fevers. See Curran et al., "Behaviors Associated With Fever in Children With Autism Spectrum Disorders" in Pediatrics Vol. 120 No. 6 December 2007, pp. e1386-e1392 (doi:10.1542/peds.2007-0360).

I note with interest that the authors of the study make no mention of earlier work showing that antibodies to heat shock protein 90 are significantly elevated in autistic individuals. See Evers et al., "Heat shock protein 90 antibodies in autism" in Molecular Psychiatry (2002) 7, S26–S28. doi:10.1038/sj.mp.4001171.

It's tempting to hypothesize that autoimmunity to hsp90 is the salient feature of autism, and that restoration of hsp90 to near-normal levels in the brain in the course of normal "heat-shock response" explains the salutary effect of fever observed by Curran et al.

Extreme Gene Transfer and Speciation, Part 3

The phylogeography of prokaryotes (indeed of microbial forms in general) has received scant study. Relatively little is known about the forces that shape microbial biogeography. Nevertheless, we do know that at the family and genus level, certain prokaryotic "regulars" are very widely distributed (geographically), despite obstacles to physical transport (and obstacles to survival during transport). For example, we can find methanogenic anaerobes belonging to the same family in anoxic lake sediments on different continents. Given the inaccessible habitats of these organisms (i.e., deep lake sediments), the fragility of the organisms with respect to exposure to air, and the unlikelihood of an organism the size of a methane bacterium migrating thousands of kilometers on its own, it's hard to explain the ubiquity of certain signature species of microorganisms around the world. Finding the same families of bacteria in the deep sediments of a lake in China, and a similar lake in North America, is tantamount to finding turtles on Mars.

The temporal dimension of the problem is just as baffling in its own way. Many landlocked microbial habitats ("disjunct refugia") have supported microbial populations for thousands, even millions of years. That's astronomical numbers of generations. Applying the concept of dog-years, we can imagine that a bacterial-year is on the order of a few human-minutes. To put it another way: in bacterial time, a month is eons. The potential for genetic drift is enormous.

And yet we find the same signature families of microorganisms over and over again, despite the huge time scales and distances involved.

Against this backdrop, it's a bit of a challenge to explain how speciation occurs in microbial flora and why the same species seem to emerge in the same types of habitats the world over. (We shouldn't get sidetracked on the precise meaning of the word "species" here. The point is that we can identify the same genomic and phenotypic motifs, packaged in readily identifiable cell types with familiar names, in different points in the biosphere.) Did today's species evolve from common ancestors who were somehow physically distributed uniformly around the world? What was the mechanism of that distribution? More to the point, what happened after the ancestral organisms were laid down? How do you get from there to today's ecosystem of commonly seen microbial communities, with its many self-similarities around the world?

I'll leave as an exercise for the reader the question of whether evolution occurred along parallel paths. I, for one, don't rule out that pseudomonads in Taiwan evolved to their present-day form independently of pseudomonads in Ohio.

I think the amazing taxonomic regularity seen in the microbial world demands flexible thinking when it comes to explaining the emergence of new species. Survival pressure keeps bacterial genomes from drifting very far outside an evolutionary "noise" zone. A substantial barrier has to be crossed in order to arrive at a new species. Accumulation of point mutations probably won't do the job. That just gives "noise." Transfection by viruses probably isn't an important mechanism, either, although the jury is certainly still out on what role (if any) viruses play in speciation.

My suspicion is that "extreme gene transfer" (including inter-species DNA transfer) plays a greater role in microbial speciation than is presently assumed. The bacterial genome inside Drosophila (see prior blog) is a clue that shouldn't be dismissed. DNA is probably more promiscuous than most of us are willing to consider.

Extreme Gene Transfer and Speciation, Part 2

A basic riddle of biology is how members of the same prokaryotic species can be found in so many far-removed places. For example, sulfate-reducing members of the genus Desulfotomaculum have been found in South African gold mines as well as deep basalt aquifers of Washington State. (See Baker et al., below.) On a bacterial scale, Washington State is about as far from South Africa as Earth is from Mars for you or me. Considering that the bacteria in question are bound in rock thousands of feet underground, it seems implausible that the Washington State bacteria somehow propagated to their current location from ancestors living in South Africa (or vice versa).

What are the possible explanations, then?

The easiest is creationism: A Higher Force created these organisms in situ, just as they are, when the Earth itself was created.

Another is panspermia: Some natural force (as yet unknown) caused all of Earth's microhabitats to be seeded with the same types of organisms, at the same time.

A third possibility is genetic convergence: All of the bacterial species we see today evolved independently, in separate locations, in parallel manner, starting from some unknown number of (possibly common) ancestors.

I say possibly common ancestors because yet another possibility exists, which is that given a sufficiently complex local ecosystem, a new member of the ecosystem can emerge on its own through mixing and matching of "borrowed genes" from existing species. Here's the thought-experiment: Imagine that we have a soil sample, and imagine that through some combination of suitable experimental techniques (remember, this is just a thought experiment) we can enumerate all of the different microbial species present in the soil sample. Homogenize the soil sample and divide it in two. Suppose there are 357 prokaryotic species in the sample, and 10 of them are Bacillus species. Now suppose you can completely eradicate all 10 Bacillus species from one of the two samples. (Pretty hard to do, but again, this is a thought experiment.)

Add water and nutrients to each soil sample (separately so as not to cross-contaminate them) on a daily basis. Prediction: After a sufficient period of time, one or more Bacillus species reappears in the soil that previously had none.

A bacteriologist will complain that this is not a terribly strict experiment, because even if a Bacillus cell were to evolve "out of nothing," it probably actually would come about through modification of a preexisting Clostridium species in the soil. (Clostridia are close relatives of Bacillus.)

Fair enough. Repeat the experiment with Pseudomonas instead of Bacillus.

The point is, if the environment favors the existence of Bacillus, the experiment will eventually find Bacillus emerging "from nothing." Or at least that's the hypothesis. A new organism, from borrowed genes.

Sounds a bit fanciful, doesn't it?

It does, until you start to read about things like an entire bacterial genome having been found within the genome of a fruit fly (Dunning-Hotopp et al., cited below.)

(to be continued)


References

1. Brett J. Baker, Duane P. Moser, Barbara J. MacGregor, Susan Fishbain, Michael Wagner, Norman K. Fry, Brad Jackson, Nico Speolstra, Steffen Loos, Ken Takai, Barbara Sherwood Lollar, Jim Fredrickson, David Balkwill, Tullis C. Onstott, Charles F. Wimpee, David A. Stahl (2003): "Related assemblages of sulphate-reducing bacteria associated with ultradeep gold mines of South Africa and deep basalt aquifers of Washington State," Environmental Microbiology 5 (4), 267–277. doi:10.1046/j.1462-2920.2003.00408.x

2. Dunning-Hotopp, Clark, Oliveira, Foster, Fischer, Torres, Giebel, Kumar, Ishmael, Wang, Ingram, Nene, Shepard, Tomkins, Richards, Spiro, Ghedin, Slatko, Tettelin & Werren. Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes. Science doi:10.1126/science.1142490