GENE SCULPTING: OF MICE,MEN;APE AND ESSENCE

Sci Tech Gene sculpting: of mice, men; ape and essence WHEN IN 1975, graduate student Mary Claire King at Berkeley, California compared the DNA of chimpanzees and humans, she obtained the surprising result that the two are 98.5 per cent identical. This led the biologist Jared Diamond to dub us humans as the Third Chimpanzee. (The other two are the two Pan chimps, one to the right bank of the Congo river, which is the common chimp, and the other `the left bank chimp' or the bonobo). The result tied in pretty much with what Charles Darwin had suggested in the 1860s that the descent of man has been from the ape. King did not go into the details of the sequences of the DNA in the genomes of the chimp and man. It was not possible then in 1975 to do so. Since then, technology and tools have become available to read out the sequence, letter by letter, of the genomic books of life of various organisms - microbes, plants, worms, mammals and man. The genomes of the mouse and man have been decoded and that of the chimpanzee is fast nearing completion. A draft version of the sequence of 3.1 billion bases of a single male chimp's genome has now been put on line by an American consortium of biologists. The draft of the 3.2 billion units-long human genome sequence is already on line. This development plus the also available mouse genome sequence has led a group of university researchers collaborate in the scientists at the Celera group of companies (of the human genome `private' initiative fame) to compare in detail 7600 genes shared by mouse, chimp and man. Their report appears in the 12 December 2003 issue of Science. Changes and divergence in DNA sequences can arise by random drift, or can be driven by evolution or through natural selection imposed by the environmental conditions. It is the latter that is of interest when we want to understand how close (or how different) we are to the chimps, and what we lost and what we got. And likewise, as mammals evolved from the mouse to the monkey and man. The way molecular geneticists do so is to choose a large number of genes that mammals - seniors and latecomers in the saga of evolution - share, and find out the ones that have changed to offer special survival advantage to each of the latecomers. Michele Cargill and her colleagues chose as many as 7600 genes shared by the mouse, ape and man and analyzed them using two statistical tests in order to identify the genes that have undergone `adaptive protein evolution'. The emphasis on proteins is because they are the workhorses or action molecules in cells, which facilitate metabolism, growth and development. Such analysis revealed that as many as 1547 human genes and 1534 chimp genes (and hence the proteins they code for) had experienced relatively rapid changes (in comparison to the mouse genome) that most likely endowed these species a survival advantage. In other words of the 7600 common to mouse, ape and man, 1547 were `sculpted' by natural selection pressure to endow `humanness' (leaving rest 6053 as those of mice and men), and 1534 sculpted to generate `chimpitude' (ape and essence). Both the chimp and human are now known to have come out of a common ancestor about 5 million years ago. Now the group compared the 1547 and 1534 to find that the changes in the chimp genes took on a path different from the route of change of human genes. The selection pressures of the environment have, presumably, been different for the two species. The family tree is the same but the branching different, making apes and humans cousins - once removed and not `sahodhara', namely, of the same womb. The group next looked at the groups of genes involved in body development, digestion and metabolism of metabolites like amino acids, signalling of cells to make tissues, and sensory perception such as sight, hearing and speech. Such comparison of the chosen ape and human genes suggested to them that the different life styles of chimps and humans might have led to divergent selection pressure on these. For example, when they compared the 48 genes responsible for endowing the sense of smell (olfaction and protein machinery involved in it), 27 of them showed rapid changes in humans. Several of the olfaction genes in humans are seen as `pseudogenes' - they are disabled and unable to make proteins. The sense of smell in man is thus somewhat inferior to that of the ape or the mouse. Of the 21 genes responsible to bestow the sense of hearing (tectorial genes), 3 of them have likewise undergone accelerated changes in man, in comparison to the chimp. On the other hand, the genes involved in the development of muscle, bone, blood and cartilage structures have gone through accelerated changes in the chimp. The study also confirmed an earlier report that the genes responsible for the development of speech have experienced unusually rapid changes in humans compared to the chimp. While this would seem obvious to us since we speak well, and in about thousand tongues at that, the chimp does not, it is reassuring and indeed enlightening to take a peek at what might be the biological driving force. It is clear that while comparing and contrasting the genomes of mouse and the primates has given us some insights, a direct comparison of the chimp genome (once it is completely decoded and available) and the human genome would be exciting and help us understand a bit more about what has made us human. It is also important to note that what these authors have done is to compare only protein-coding genes. There are other sequences that regulate gene expression, or control which genes should be turned on or off, when and where. These are just as important and would likely have had a role in branching the human lineage off the chimp's. The 1.5 per cent genetic difference between the two will then become even more understandable.