Werner Arber on Genetic Variation-Three Strategies
  Werner Arber     Biography    
Recorded: 08 May 2012

Really it is looking at the whole genome and we at that moment already had started, and other people had started, work on transposable elements. And of course recombinant was known, and horizontal transfer was known. So, at one time I kind of made a synthesis of all that knowledge and saying that there’s a multitude of different specific mechanisms in which—to which often gene products contribute either as variation generators, for example recombination enzymes, or as moderators of the rates of genetic variation in order to ensure that the living world has a relatively good stability, but not full stability. Still allowing evolutionary adaptations. And that came up with the conclusion that all these mechanisms on which enzymes are involved and also non-genetic elements, such as structural flexibilities or stabilities of some of the biomolecules, and so on. Or, the impact of an external mutagen, chemical or radiation mutagen, and so on. We kind of grouped—I called that into three strategies of nature, natural strategies, not of the researchers. One is occasionally introducing just a local change, meaning one or a few adjacent nucleotides are changed, are intermingled, or deleted, or adding one. That’s a local change.

Okay, the strategies are local, intra-genomic, rearrangement of segments, that can be duplications, can be deletions, inversions of a segment, depending of course. One of the ways to do such is by transposition of transposable elements, or also by site specific recombinations. We later on found out that in site specific, site specific means you recombine at very particular nucleotide sequences, but they do that recombination—enzymes do that also, at much lower frequencies at many other, what we call secondary sites of crossing over. And that’s the source of fusion of domains of different genes, and occasionally that can have some new function, or you bring by, for example, DNA inversion, you bring all of the sudden a control element for gene expression near a reading frame, and give out expression control.

Well, the third, I should say, is the horizontal transfer, which is also quite important, because in horizontal transfer the quality of the contribution to the evolution of the three strategies is different. In local modifications you may have a chance to slightly improve something existing. In intra-genomic recombination you may, as I mentioned for example before, make a new structure which wasn’t there before, but from existing material. And in the third strategy, you acquire something which some distant living organism has constructed in evolution and you actually benefit from the other organisms success, evolutionary success.

Werner Arber, (born June 3, 1929, Gränichen, Switz.), Swiss microbiologist, corecipient with Daniel Nathans and Hamilton Othanel Smith of the United States of the Nobel Prize for Physiology or Medicine for 1978. All three were cited for their work in molecular genetics, specifically the discovery and application of enzymes that break the giant molecules of deoxyribonucleic acid (DNA) into manageable pieces, small enough to be separated for individual study but large enough to retain bits of the genetic information inherent in the sequence of units that make up the original substance. Arber studied at the Swiss Federal Institute of Technology in Zürich, the University of Geneva, and the University of Southern California. He served on the faculty at Geneva from 1960 to 1970, when he became professor of microbiology at the University of Basel. During the late 1950s and early ’60s Arber and several others extended the work of an earlier Nobel laureate, Salvador Luria, who had observed that bacteriophages (viruses that infect bacteria) not only induce hereditary mutations in their bacterial hosts but at the same time undergo hereditary mutations themselves. Arber’s research was concentrated on the action of protective enzymes present in the bacteria, which modify the DNA of the infecting virus—e.g., the restriction enzyme, so-called for its ability to restrict the growth of the bacteriophage by cutting the molecule of its DNA to pieces.