The primate α-globin gene family: A paradigm of the fluid genome

The α-globins are an extraordinarily useful model for analyzing the dynamic processes that produced the human genome and that still occur within it, most of which could hardly have been imagined 20 years ago. We are approaching problems of genomic turnover from a structural, biophysical, and cellular perspective, in the hopes of deepening our knowledge of the mechanisms involved in these recombinations. Nevertheless, it is always possible, in the highly focused realm of molecular studies, to lose sight of the larger spectacle of phylogeny and evolution. We appreciate that our work interfaces with other disciplines, such as systematics, primatology, and biological anthropology, and that interchange can be mutually illuminating. The θ1 gene was discovered first in the orangutan because the human α-cluster had proven difficult to clone downstream from α1, and all the known globin proteins were accounted for genomically and there seemed no reason to expect anything of interest to exist there. By focusing our attention not only on genomic evolutionary processes, but on their evolutionary products in other closely related species as well, we have been able to frame and test hypotheses about the structure of the human genome, and reciprocally to make inferences about the processes themselves. It is now obvious that the genome is not the stable entity it was once considered to be. On the contrary, it is in a fairly constant state of flux. The 30-kb stretch comprising the human α-globin cluster affords us a window through which we may glimpse the genomic turnover processes operating, model them, and, in the end, gain a deeper understanding of the cryptic factors that govern the genetic evolution of our species.