Did you know that badly folded proteins could be the cause of our species’ destruction? Neither did I.

I know about nuclear bombs, climate change, asteroid strike and even pandemic as possible doomsday scenarios. I’m aware of predictions that in the not too distant future mankind might be overpowered by or merge with artificial intelligence (the Singularity). I know of plenty science fiction tales of ‘gray goo’ or some other nanotechnology disaster. In fact, to be honest, I’m becoming somewhat inured to the various ideas of how human beings could cease to exist. “Yeah, yeah…tell me about it next week.”

So when a couple of major science publications run a relatively brief article, Nature News 11-May-2011, paywall [The Achilles’ heel of biological complexity] and Scientific American 12 May 2011, paywall [Why Are You So Complex? Complicated Protein Interactions Evolved to Stave Off Mutations] which states:

…it may be a losing battle. Genetic drift may eat away at the ability of our proteins until they are overwhelmed, leaving us a sickly species.
…
“Species with low population are ultimately doomed by nature’s strategy of evolving complexity.”

I don’t get all that stressed. Neither does the article. Yet…the story is interesting in how it casts light upon a little discussed aspect of biology, the behavior of our proteins (and the field of proteomics), and their importance to life.

I’ll tell you that one factor in a doomsday scenario I was not expecting is that there are too few people. As we approach the 7 billion mark in population that seems far-fetched. However, compared to bacteria – where 7 billion of a thousand species might live in a pool of water – we don’t have a very large genetic population (i.e. gene pool). This leaves us exposed to what biologists call genetic drift.

Genetic drift occurs when a genetic mutation is carried by reproduction of genes merely by chance, and is not subjected to the winnowing process of natural selection. Biologists have known about genetic drift for many decades, but its significance was a matter of controversy. It was generally thought until the 1970’s that natural selection was far more important. What it eventually boiled down to is that in large populations natural selection and genetic drift are both active and essentially balance out. In small populations, genetic drift wins by the numbers. In this game of genetic chance, human beings have a small population.

This means that a detrimental genetic mutation isn’t necessarily removed from the human gene pool; in fact, it can continue to spread through genetic drift. In this case, the concern is with mutations to the ability of proteins to take required shapes and perform their required functions.

Proteins are the building blocks of life. They are manufactured in every cell under the guidance of DNA. How they work depends not only on their chemical composition (huge chains of amino acids called polypeptides), but also on their shape (their configuration or folding). A protein works because it has the right chemical properties and also the right shape. When proteins ‘misfold’ bad things can happen such as Alzheimer’s disease, Parkinson’s disease and prion diseases.

Normally proteins in animal cells sort of stick together (not a scientific term, I know), which has the effect of hiding or sheltering portions of the protein that are water-sensitive (generally hydrophilic, attracting water molecules). Scientists believe this evolved so that the shape of a protein would not be affected by intruding water molecules. Over the eons, however, as mutations continued to change how proteins were constructed, the protein-to-protein properties that protect the shape became increasingly complex. At some point, they began to be too complex to ‘fix’ – certain mutations changed the proteins so that water molecules could access the hydrophilic portions of the protein – and the shape would change. The most obvious example of this problem are prions, water-logged proteins so poorly constructed that they lose their shape (folding) and cause other proteins to do the same. There are many prion related diseases, such as ‘mad cow disease’ and Creuzfeldt-Jakob disease in humans.

Where is this leading? To some scientists this looks like a dead-end development. In humans, at least, the ability of proteins to use complex behavior to protect against genetic mutations has its limits. Random drift then ensures that mutations spread throughout the population, unchecked by natural selection. The worst case is that some prion-like mutation creates a disease that in pandemic fashion reduces the human population below the survival level. Translated, that means species extinction.

Of course, these ideas are controversial. The hypothesis that proteins stick together to protect their shapes and that this is an evolutionary defense mechanism against genetic drift needs much more work. The science is even further away from finding a true doomsday situation. So, scary predictions aside, the significant impact of this hypothesis may be to continue shifting focus to the importance and intricacy of proteins – the study of proteomics. It seems that proteins have spent too much time in the shadow of genetics and DNA, when in fact they have a world of their own – including epigenetics, the development of genetic-like properties outside DNA. Maybe a scary scenario is just what is needed.