Blast from the past

In my senior year at Delaware I took a course in molecular evolution from a wonderful teacher, Hal Brown. Hal was the first (I'm pretty sure) to suggest that resemblance of many enzyme cofactors to RNA was a glimpse at an earlier RNA-dominated biochemistry. Another interesting brush with history is that when at Berkeley he got Dobzhansky's desk. He's a great guy & was a wonderful professor.

I had Hal's class fall semester that year, and still was planning to continue my undergraduate research line of molecular biology in a plant system; my overnight mental conversion to a computational genomicist wouldn't occur until Christmas break. So I picked a term paper topic that sounded interesting (and was!), but in retrospect was a glimpse at my future.

Very few eukaryotes have a single genome, as most have membrane-bounded organelles with their own genomes. For mammals, these are the mitochondria, and in plants and alga there are both the mitochondria and chloroplasts. The fact that chloroplasts and mitochondria had their own genetics, which had quirks such as uniparental inheritance, had been known since the early 60's, but their origin had been hotly disputed. The original theory that they had somehow blebbed off from the nuclear genome had been challenged by Lynn Margulies' radical notion of organelles as captured endosymbionts. By the time I wrote my paper, Margulies thesis had pretty much won out. But it still made a fascinating paper topic, especially when thinking about genomes.

The most fascinating thing about these organelle genomes is not that they have shed many genes they no longer need, as those functions are provided by the nucleus, but the real kicker is that so many genes for their maintenance & operation are now found in the nucleus. Over evolutionary time, genes have somehow migrated from one genome to another. For metazoan mitochondria, the effect is striking: only a tiny number of genes remain (human mitochondrial DNA is <20kb>100Kb were either viruses or complete plant chloroplast genomes, so there was some real data to ponder -- my first flicker of genomics interest.

One strong argument for the endosymbiont hypothesis is an unusual alga with the appropriate name Cyanophora paradoxa, which has chloroplast-like structures called cyanelles -- but the cyanelles retain rudimentary peptidoglycan walls -- just like the cyanobacteria postulated to be the predecessors of chloroplasts. Another strong argument is that for a set of enzymes found both in organelle and cytoplasm, in most cases the organellar isozyme treed with bacterial enzymes (and in the right group: proteobacteria for mitochondrial enzymes, cyanobacteria for chloroplast ones). Even the exceptions are interesting, such as a few known examples where alternative transcripts can generate the appropriate signals to lead to cytoplasmic or organellar targeting.

I hadn't really kept up closely with the field after that (not for lack of interest: one graduate posting I considered was on a Cyanophora sequencing project at Penn State). So it was neat when I spotted a mini-review in Current Biology on the current state of things. What is interesting, and new to me, is that the Arabidopsis sequencing effort had revealed that nuclear-encoded proteins of chloroplastic origin covered a wide spectrum of metabolism and not just chloroplast-specific functions. What is interesting in the newer work is that Cyanophora does not share this pattern: here nuclear-encoded genes of chloroplast origin are strongly restricted to functioning in the chloroplast.

Things get even wierder in some other unicellular creatures, which executed secondary captures: they captured as endosymbionts eukaryotes which had already captured endosymbionts.

The same issue contains some back-and-forth arguing over the distinction between organelles and endosymbionts, which I don't care to take a stand on, but they illustrate another case I wasn't very familiar with: a sponge which has apparently taken in an algal boarder. If we can figure the mechanisms out & replicate them, the applications might enable some people to truly be 'in the green' and 'looking green around the gills' will take on a whole new meaning!