Historical Constraints and the Evolution of Development 1097
and throughout the abdomen (see Fig. 10-15), Lewis assumed that the functional
basis of duplication lay in the need for more genes to achieve evolutionary
differentiation from the ancestral homonomy of repeated and similar (if not identical)
appendages on each body segment—in this case, and for dipterans in general, to
suppress the development of legs on abdominal segments and to convert the second
pair of wings (on the third thoracic segment) into the small pair of balancing halteres.
The model then implied an elegant mechanism for gene functioning in
morphological differentiation. Lewis argued that the first gene in the array turned on
in the second thoracic segment and in all posterior segments, with each subsequent
gene having its anterior boundary of expression one or two segments further back,
but then turning on from there to the posterior end of the fly. Clearly, such a system
would build a simple and linear gradient with least gene product at the anterior end of
expression for the entire array (where only the first gene turns on), and most products
at the posterior end of the animal (where all genes are active).
The further beauty of this model then lies in the simple testability of the implied
10 - 15. E. B. Lewis's original, brilliant, but not entirely correct model for developmental action
of genes in the bithorax complex of Drosophila. Lewis assumed that differentiation of
complexity from original homonomy, particularly the conversion of the second pair of wings
to halteres, and the suppression of legs on the abdominal segments, required a duplication of
further genes in the set. He proposed a tandem array of up to eight genes, each turning on in
sequence, but with expression beginning in successively more posterior parts of the developing
larva—thus establishing a gradient with ever more gene product accumulating towards the
rear of the animal. Therefore—and this part of the model remains basically correct—loss-of-
function mutations should weaken the gradient and cause anterior structures to develop in a
more posterior position; while gain-of-function mutations should intensify the gradient and
cause posterior structures to develop in more anterior sites.