Molecular cytogenetics is hardly my field, so this paper was a bit hard for me, but the results were so interesting that I’ll do my best to present it. The paper is by Quingua Zhou et al. and was just published in the early, non-print edition of Science. (reference and free download below). It’s about what happens to mitochondria in embryos. There’s another paper in the same issue that shows the same thing, by S. Al Rawi et al, (reference below), but I didn’t read that one. There’s also a perspective on both papers by Beth Levine and Zvulun Elazar, which I also haven’t read (I’m busy!)
As you may remember from your biology courses, mitochondria are “organelles” in the cell that function in respiration and metabolism (the generation of energy) and in “apoptosis,” or programmed cell death. They contain a circular DNA molecule that produces gene products (proteins) as well as transfer RNAs—the small molecules that lock onto amino acids and help assemble them into proteins. One of the big findings of my lifetime, suggested by Lynn Margulis among others, is that mitochondria are actually the evolutionary remnants of bacteria-like prokaryotes that were ingested (probably by another prokaryote), forming a mutualistic relationship that led to the first “true” cell: a eukaryote.
The interesting thing about mitochondria is that in nearly all sexually reproducing species they’re inherited purely maternally: while both mother and father have them, only the mother’s mitochondria are passed to its adult offspring. This is why, for instance, we’re able to identify a “mitochondrial Eve”: the ancestral woman from whom all the mitochondrial DNA of living humans is descended. (Of course the rest of our DNA, which is far greater in extent, comes from a diversity of other “Eves,” so this doesn’t support the Biblical narrative in any way.)
Although a late-stage developing embryo contains only the mitochondria from the mother, sperm that penetrate the egg do have paternal mitochondria, and, at least in the “model organism” studied (the tiny worm Caenorhabditis elegans), they are present in early embryos. But then something happens—something that is amazing. You can see it happening in the photograph below.
The first photo, “A,” shows normal mitochondria in C. elegans sperm. B-C are the paternal mitochondria, derived from sperm, in embryos. Shortly after the embryo is formed, abnormal aggregates begin to form in those mitochondria (blue arrows; scale bars are 300 nanometers, or 0.3 microns, long). The cristae, or internal mitochondrial membranes, begin to break down (B & C). Then an “autophagosome” (yellow arrow) begins to form around the paternal mitochondrion (C); this is a membrane that the cell puts around structures that it intends to destroy. The contents of the autophagosome are subsequently degraded by special organelles called lysosomes. In photo “D”, the mitochondrion is on its way out; its membrane has broken down and it will soon degenerate. The paternal mitochondria are all destroyed in this way. Only the maternal ones remain as the embryo develops into an adult worm.
There are four questions here:
- Why does the embryo destroy the paternal but not maternal DNA? There are evolutionary theories for this based on preventing the spread of selfish DNA in organelles (see here for one example), but these are only untested speculations. But there is almost certainly some evolutionary reason for it, since uniparental inheritance of mitochondria is so common.
- How does the embryo distinguish between paternal and maternal mitochondria, and destroy only the former? Short answer: we don’t know. But I bet we will within a few years.
- What are the genes involved in the destruction of paternal mitochondria? The authors of the Zhou et al. paper answered that one using clever techniques. By genetically removing RNA of genes involved in mitochondrial membrane production, they showed that one gene, cps-6, is probably involved. When the RNA product of that gene is deleted from the embryo, the paternal mitochondria persist until the late embryo stage, something that doesn’t happen with the product of any other gene. It turns out that the cps-6 gene is a nuclease (it destroys chains of nucleotides, like RNA and DNA) and is imported into paternal mitochondria by the cell, where it breaks them down.
- What happens to the cell if paternal mitochondria aren’t destroyed? If you inactivate the cps-6 gene so that paternal mitochondria remain in the embryo intact, there’s elevated mortality of those embryos. It’s not total, but increases by 5.9%—a serious loss of offspring in evolutionary terms. This suggests that it’s to the cell’s advantage to destroy paternal mitochondria, and directs us again to an evolutionary explanation, one still not fully understood.
Zhou, Q., H. Li, H. Li, A. Nakagawa, J. L. J. Lin, E.-S. Lee, B. L. Harry, R. R. Skeen-Gaar, Y. Suehiro, D. William, S. Mitani, H. S. Yuan, B.-H. Kang, and D. Xue. 2016. Mitochondrial endonuclease G mediates breakdown of paternal mitochondria upon fertilization. Science, published online: DOI: 10.1126/science.aaf4777
Al Rawi, S., Louvet-Vallee, S., Djeddi, A., Sachse, M., Culetto, E., Hajjar, C., Boyd, L., Legouis, R., & Galy, V. (2011). Postfertilization Autophagy of Sperm Organelles Prevents Paternal Mitochondrial DNA Transmission Science, 334 (6059), 1144-1147 DOI:10.1126/science.1211878