We have reached a stage where the amount of studies that describe the function of a particular gene in a particular model organism and under particular conditions has become unmanageable. At the same time, articles that describe a completely new cellular mechanism that may occur in all animal and plant cells, but has remained hidden so far, became extremely rare. That's why the two articles that appeared in the journal Nature last week are so special. And to understand what makes them special, we need to have a closer look on a paradoxical observation in the field of genetics that has become more prevalent over the last few years.

Genetic engineering methods such as CRISPR nowadays allow the targeted mutation of a gene, so that the function of the encoded protein is completely lost. This is called a genetic knock-out. Other methods, such as the use of RNA interference, allow the downregulation of gene function by blocking the mRNA transcript of the corresponding gene or initiate their degradation. As a result, the translation of these mRNA molecules is disturbed, so that much less of the corresponding protein is formed. However, a few functional molecules remain, which is why we call those methods knock-down procedures. Absurdly, however, it was repeatedly observed that these knock-down approaches lead to a stronger effect than the previously mentioned knock-out approaches, which nevertheless lead to a complete loss of the protein under investigation. How is that possible? This remained a mystery for quite some time…

Virus: CowpeaMosaicVirus3D by Thomas Splettstoesser for wikimedia.org, CC-BY-SA-3.0

The year 2018 is about to end and it was yet another extremely eventful year for molecular biology and biomedicine. CRISPR has captured the headlines around the globe. But not every piece of research that has caused a sensation and astonishment this year has been directly related to CRISPR. As early as January 2018, two articles were published in the same issue of the journal Cell, which was jaw-dropping for several members of our working group, including myself. Back then - due to an acute lack of time - I did not manage to explain why these two articles had such an effect. Anyway, here finally is the long overdue article on the ARC gene and the question about whether an evolutionarily ancient virus(!), could be responsible for us being able to remember things so well.

It took a while, but now the newspapers are filled with it: at the initiative of the states of Baden-Württemberg and Bavaria, the German Bundesrat recently had a draft for a far-reaching change in the law (printed matter 117/17; in German). It's about expanding the scope of investigations of so called "DNA-capable material". To date, German investigators have been allowed to compare a DNA sample saved at a crime scene with a database to determine a potential immediate match. If necessary - and only after court approval - the police can also ask a larger group of people to provide their DNA to verify their identity to the seized DNA. If this procedure does not lead to a hit, in a German criminal case usually the utilization of the DNA trace ends at this point. But, wouldn't it be possible to gather information on the origin, stature, skin, hair or eye color of an unknown person from it's DNA? And if so, why can't the German officials do that so far? And isn't it time to change this situation?

When in 1979 six research groups independently described a 53 kDa protein, none of the participants suspected to which genetic superstar this protein would develop. This protein, which due to its molecular weight was given the not-so-impressive name p53, is perhaps the most important policeman in our cells; but only as long as it works properly. If p53 loses its functionality, it’s getting pretty dangerous. In fact, no other gene is mutated more frequently in tumor cells than p53. So how does normal p53 manage to keep all of our body cells in check and what does it all have to do with CRISPR?

When I started researching this week's article, I was amazed myself. EPAS1 is a really fascinating protein. So I'll do my best to try and tell you what is so special about EPAS1. Only so much in advance: it has to do with Tibetans, athletes, oxygen and a long extinct human species. In fact, the only uninteresting thing about EPAS1 is its full name: endothelial PAS domain-containing protein 1. What was breathtaking, in contrast, was the observation that Tibetans almost exclusively carry a certain variant of the EPAS1 gene, which hardly ever occurs in Han Chinese (published in 2010 in science). In fact, the unequal distribution of these two variants between the two populations, which split only a few thousand years ago, is as high as has ever been observed for any other human gene. So what environmental factor could it be that has made this gene evolve so incredibly fast? There is very good evidence that it is the extraordinary sea level of Tibet. Even Tibets capital Lhasa is located at almost 4000m, a height in which a human being during normal breathing absorbs one third less oxygen than at sea level. Most Tibet travelers (whether Europeans, Americans or Han Chinese) respond to this with a full-blown altitude sickness.