The Human Factor
Now that the human genome is known in its entirety, it must be possible to find it: the gene that makes humans human. In fact, a prime suspect has now been identified - even if it's not a "real" gene.
"Light will fall on man and his history," Charles Darwin once prophesied. For the founder of the theory of evolution it was clear that man can only be the result of his own evolution. But what makes a human a human? Ultimately, the answer must lie hidden in his genetic make-up.
150 years after the publication of Darwin's seminal work, On the Origin of Species, geneticists finally have the means to tackle this question: the (nearly) fully deciphered human genome. The almost three billion building blocks should contain hereditary factors that only exist in their special form in the species Homo sapiens. The fact that we share 99 percent of our genome with our closest relative-the chimpanzee-limits the search somewhat.
And there are already candidates for typical human genes – like FOXP2, which is said to play an important role in human language, or ASPM, which is involved in brain maturation. But these genes are more or less similar in our monkey cousins.
The researchers led by David Haussler from the University of California in Santa Cruz have now systematically investigated the matter: They trawled through the chimpanzee genome, which had also been deciphered, for regions that over a distance of one hundred base pairs were at least 96 percent identical with the corresponding Sections in the mouse and rat genome are identical. These ranges - about 35,000 in total - can therefore be considered highly conservative, where little has happened in mammalian evolution.
The task now was to fish out those sections of the human genome that have changed more here than would be expected from the normal genetic drift since the separation between humans and chimpanzees.
The result: A total of 49 regions – called HARs (human accelerated regions) by the researchers – deviate significantly from the corresponding chimpanzee counterparts. The clear winner - the 118 base pair region HAR1 - has changed at 18 positions in humans; 0.27 substitutions would be statistically expected. In contrast, HAR1 differs between chicken and chimpanzee in only two places. In other words, almost nothing has changed here since the last common ancestor of mammals and birds - who walked the earth an estimated 300 million years ago. That changed dramatically when man's ancestor went his own way about six million years ago.
Now what do these human factors do? Interestingly, only two of the 49 regions contain building instructions for proteins, so they are "real" genes. The remaining 47 belong to the enigmatic non-coding "dark matter" of the genome, which makes up 98.5 percent of the entire genome.
The candidate HAR1 on chromosome 20 is also one of these. The researchers were able to identify two regions here - HAR1F and HAR1R - which do not code for a protein, but each code for an RNA. The researchers do not yet know what task these RNAs perform. However, there were indications that HAR1F plays an important role in embryonic brain development: the gene is transcribed in seven to nine-week-old embryos – in the developing cerebrum. In particular, the Cajal-Retzius cells, named after the anatomists Santiago Ramón y Cajal and Gustaf Magnus Retzius, which produce the protein Reelin, which is important for brain maturation, proved to be particularly good HAR1F candidates.
So is this the key to humanity? Maybe. As long as the role of HAR1F is not clear, there is still much room for speculation.