Migrating genes

I've been talking quite a lot about mitochondria lately. The fact that these organelles contain their own DNA (called mtDNA) and were the result of a horizontal gene transfer during evolution is simply fascinating. And I know many of you agree, as proved by the wonderful questions my last post on mitochondria sparked (thank you Hollis and Marleen!)

Plastids, plant organelles that are responsible for photosynthesis, also have a circular, double-stranded DNA molecule (called ptDNA). Like mitochondria, plastids originated through endosymbiosis and, in most plants, are inherited from one parent only. Now, here's another fascinating fact:

"During the early phase of organelle evolution, organelle-to-nucleus DNA transfer resulted in a massive relocation of functional genes to the nucleus: in yeast, as many as 75% of all nuclear genes could derive from protomitochondria, whereas ~4500 genes in the nucleus of Arabidopsis are of plastid descent. Cases of present-day organelle-to-nucleus DNA transfer, revealed by the presence of NUMTs and NUPTs [the fraction of nuclear DNA that derives from mitochondria and plastids respectively], are known in most species studied so far. [...] Mitochondrial chromosomes contain segments homologous to chloroplast sequences, as well as sequences of nuclear origin, providing indirect evidence for plastid-to-mitochondrion and nucleus-to-mitochondrion transfer of DNA [1]."

Throughout evolution transfers of genes between plastids and mitochondria have been documented, although in present organisms these transfers gave rise to non-functional sequences. In plants, the transfer of genes from organelles to nucleus seems to be still active, as documented by the RPS10 gene, which is present in the mitochondria of some angiosperms, and in the nucleus of other plants [Henze and Martin, 2001]. In fact, orgenelle-to-DNA gene transfers have been studied extensively in plants: their cells have both plastids and mitochondria and, as a consequence, they are in general more informative than animal eukaryotes.

In [1], Leister revises studies that show that mtDNA in Homo sapiens integrates continuously into the nuclear genome, as both de novo and pre-existing nuclear insertions of mtDNA have been documented. Recent acquisition of nuclear mtDNA have been documented by comparison with chimpanzee genomes.

So, how do these transfers happen? Though it was originally thought that genes would migrate as RNA transcripts, new studies have shown that it's the DNA itself that "escapes" the organelle:

"Escape of organelle DNA and its uptake into the nucleus has been experimentally demonstrated in yeast and tobacco."

Once these bits of DNA arrive to the nucleus, however, they are subject to a much lower mutation rate than they were in their original location. What this means is that mutations appear more rarely in the nucleus than they do in the organelles. As a consequence, they become "conserved," undergo very little changes, and, at all effects, become "molecular fossils," allowing researchers to retrace phylogenies between species.

"Moreover, nuclear organelle DNA insertion polymorphisms, as a subclass of insertion-deletion polymorphisms, are valuable markers for population and evolutionary studies."

Since the process of migration from organelle to nucleus is a constant one, studies have been directed at measuring the rate of continued colonization of organelle DNA into the germline. The rate in humans has been found to be of the order of 10e-05, and even though these insertions in the past had been thought to be essentially harmless, recent studies have confirmed associations with certain types of hereditary diseases. As I was discussing last week, more studies are in the way to investigate possible associations between nuclear mitochondrial polymorphisms and certain types of cancers.

[1] Leister, D. (2005). Origin, evolution and genetic effects of nuclear insertions of organelle DNA Trends in Genetics, 21 (12), 655-663 DOI: 10.1016/j.tig.2005.09.004