It’s even odder to think that each one of us has been colonised by organisms that probably developed around the same time our ancestors were diverging from the forebears of modern bacteria. ‘Colonised’ is really an understatement. Our entire survival and that of every other multicellular organism on this planet from grass to zebras and from whales to worms relies on this colonisation. It’s even true of the yeast we depend on for bread and beer.
Billions of years ago the cells of our earliest ancestors were invaded by tiny organisms. At this stage there probably weren’t any organisms more than four cells in size and the four cells would have been pretty non-specialist. Instead of warring against each other, these cells and their tiny invaders reached a compromise. Each benefitted from the compromise and so a beautiful friendship, lasting billions of years, was born.
These tiny organisms evolved into critical components of our cells called mitochondria. The mitochondria reside in the cytoplasm and are little power generators. They are the sub-cellular organelles that produce the energy we need to power all of our standard functions. It’s the mitochondria that have allowed us to make use of oxygen to create useful energy from food sources. Without them, we would be smelly little four-celled nobodies with hardly enough energy to do anything useful.
One of the reasons we are confident that mitochondria are the descendants of these once free-living organisms is that they have their own genome. It’s much smaller than the ‘proper’ human genome that is found in the nucleus. It is just over 16,500 base pairs in length compared with the 3 billion base pairs of the nuclear genome, and unlike our chromosomes it is circular. The mitochondrial genome only codes for 37 genes. Remarkably, well over half of these don’t code for proteins. Twenty-two of them encode mitochondrial tRNA molecules{222} and two encode mitochondrial rRNA molecules. This allows the mitochondria to produce ribosomes, and to use these to create proteins from the other genes in its DNA.[30],{223}
This seems a very risky strategy in evolutionary terms. Mitochondrial function is critical for life and ribosomal function is absolutely critical to mitochondrial function. So why have such an important process with no safety net of extra copies of the ribosomal genes in our power generators?
We can get away with this because mitochondrial DNA isn’t inherited in the same way as nuclear DNA. In the nucleus we inherit one set of chromosomes from each parent. But mitochondrial inheritance is different. We only inherit our mitochondria from our mother. This would seem to make for an even riskier scenario because it means if we inherit a mutant mitochondrial gene from our mother, there is no chance of a back-up normal gene from dad.
But there is (of course) a complication. We don’t just inherit one mitochondrion from our mother, we inherit hundreds of thousands, maybe even a million. And they aren’t all the same genetically, because they haven’t all originated from one mitochondrion in a previous cell. Every time a cell divides, the mitochondria also divide and are passed on to daughter cells. Even if some of these mitochondria have developed mutations, there will be plenty of other mitochondria in the cell that are fine.
That’s not to say that problems never develop, and many of those that do have been reported to be in the tRNA genes on the mitochondrial DNA. These include conditions with muscle weakness and wasting;{224} hearing loss;{225} hypertension{226} and cardiac problems.{227} But the symptoms may vary a lot from patient to patient, even within the same family. The most likely reason for this is because symptoms may not develop until the percentage of mutant mitochondria in a tissue reaches a threshold. This may not be until relatively late in life, as a consequence of random unequal distribution of ‘good’ and ‘bad’ mitochondria when a cell divides.
If all of this hasn’t been enough to demonstrate that RNA is not just some poor relation of DNA or an inferior species compared with proteins, consider this. Despite DNA being the poster child for biology, all life on earth may have originated not with DNA but with RNA.
DNA is a great molecule. It stores a lot of information, and because of its double-stranded nature it’s easy to copy and to maintain the sequence stably. But if we try to think back billions of years, to when life began to develop, it’s hard to see how it could happen based on a DNA genome.
That’s because although DNA is fantastic at storing information, it’s no use in terms of creating something from that information, not even another copy of itself. DNA can never function as an enzyme. Because of this, it can’t make copies of itself so how could it have been the starting genetic material? It is always reliant on proteins to do its bidding.
But if we look at rRNA, a molecule which has received very little by way of the spotlight even among most scientists, there’s a bit of a eureka moment. rRNA contains sequence information but it is also an enzyme. This raises the possibility that RNA could have had a range of enzymatic activities in the past, and this could have led to the evolutionary development of self-sustaining and self-propagating genetic information.
In 2009 researchers published extraordinary work in which they generated such a system. They genetically created two RNA molecules both of which could act as enzymes. When they mixed these molecules in the lab, and gave them the raw materials they needed, including single RNA bases, the two molecules made copies of each other. They used the existing RNA sequences as the templates for the new molecules, creating perfect copies. As long as they were supplied with the necessary raw materials, they made more and more copies. The system became self-sustaining. The researchers went even further by mixing higher numbers of different RNA molecules, each of which had enzymatic activity. When they activated the experiment, they found that two sequences would rapidly outnumber all the others. Essentially, the system was not only self-sustaining, it was also self-selecting because the most efficient pairs of RNA molecules would recreate each other far more rapidly than any of the other pairings.{228} Very recently, scientists have even succeeded in creating a type of enzymatic RNA that will generate copies of itself.{229}
An expression that is still heard in the UK is ‘Where there’s muck, there’s brass’, meaning that where there is dirt or rubbish, there’s money. Maybe where there’s junk, there’s life.
12. Switching It On, Turning It Up
With a mere $1,700,000 price tag, the Bugatti Veyron is the world’s most expensive production road car. It’s hard to be sure what the cheapest car is, although the Dacia Sandero probably has a good claim to this honour, at about 1 per cent of the cost of the Veyron. But both cars have a number of things in common, and one of these is that each needs to be switched on before you can go anywhere. If you don’t activate the engine systems, nothing will happen.
Our protein-coding genes are the same. Unless they are activated and copied into messenger RNA, they do nothing. They are simply inert stretches of DNA, just as a Veyron is a stationary hunk of metal and accessories until you hit the ignition. Switching on a gene is dependent on a region of junk DNA called the promoter. There is a promoter at the beginning of every protein-coding gene.
30
Mitochondria use lots of other proteins for their biochemical processes, but most of them they import from the cell cytoplasm. The ones that are uniquely encoded in the mitochondria are all involved in a process called the electron transport chain, which takes place within mitochondria themselves. This process is essential for life, as it is how we generate storable usable energy to power our cells.