The Wonder of Our Presence Here: A Commentary on the Evolution and Maintenance of Human Diversity

THE WONDER OF OUR PRESENCE HERE: A COMMENTARY ON THE EVOLUTION AND MAINTENANCE OF HUMAN DIVERSITY JAMES V. NEEL* Introduction The title of this address is deliberately ambiguous. In fact, there are not one, but many wonders to our presence here. The first is the wonder that none of us can escape as we walk the streets ofJerusalem, aware that this region is one of the cradles of civilization, with documented, probably continuous, human habitation for the past 12,000 years, and that the city in which we are meeting is seminal to Judaism, Christianity, and Islam. From no other comparably small area have concepts with greater worldwide impact originated. There is, next, a much more mundane connotation in which I use the word "wonder"; I marvel that in these difficult times so many of you have accommodated to the regional uncertainties and also that we have finally generated the financial support necessary to a Congress of this magnitude, and that it has been possible to generate a program of this scope. May I be permitted to express on behalf of all of us our deep appreciation to the many who have worked to bring this about. The wonder I wish to address is neither of these but, rather, that sense of astonishment and amazement thrust upon all geneticists by the recent revelations concerning the complexity of our biological being. I am struck with wonder, as we gather here to open this Congress, at the sequence of events which, beginning some 4 billion years ago, must have transpired to create the genetic material which enables us to undertake A shorter version of this paper was presented on September 14, 1981, as the Presidential Address at the Sixth International Congress of Human Genetics in Jerusalem, Israel. This expanded version permits a more rigorous documentation of my thesis than was then possible. *Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109.© 1982 by The University of Chicago. AU rights reserved. 003 1 -5982/82/2504-03 1 3$01 .00 518 I James V. Neel · Evolution ofHuman Diversity such a meeting as this. In what follows, let us first refresh our memories as to the nature of that complexity and the many potentialities for its undoing. Next, we will examine our limited comprehension of how this complexity is not only maintained in good working order but is able to adapt and evolve in an ever-changing world. Finally, we will consider some of the hints now emerging for new directions in our thinking. The Complexity of Our Genetic Organization There is sufficient DNA in a human gamete to accommodate approximately 2 x 109 nucleotide pairs. The remarkable advances in recent years in assigning specific functions to specific regions of the chromosome in which this material is packaged will be summarized elsewhere at this Congress (see also [I]). Shortly after the nature of the genetic material became known, a number of geneticists made the obvious calculation that, if the average protein was a polypeptide composed of 300 amino acids, the requisite information could be carried by less than 1,000 nucleotide pairs, so that we humans have the coding potential for some 2,000,000 proteins. Since no one seems to believe humans have need for more than some 50,000 different proteins, then even with a seemingly generous allowance for the necessary nuclear "control" apparatus , the arithmetic suggested we might have DNA far in excess of our needs, and there was a rash of speculation about "junk DNA," an unnecessary and unloved relic of our evolutionary past. As in the past 10 years the true complexity of genetic organization has begun to emerge, it is clear no generalization was ever more premature, a tribute to our incurable intellectual arrogance in the face of the unknown. Let us consider very briefly one example of the complexity of organization and function of the DNA, the still unfolding story ofthe ?-8-ß and a hemoglobin loci (reviewed in [2-8]). Figures 1 and 2 depict what genetic fine structure analysis has revealed concerning the organization of the DNA in the regions in which the ?-8-ß and a hemoglobin structural genes are found...