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Scientific Serendipity Initiates an Intron Odyssey

M. Belfort

Published 2009 in Journal of Biological Chemistry

ABSTRACT

As the child of German immigrants to South Africa and disillusioned by the Apartheid regime, I made my way to the United States for graduate school. After earning my Ph.D. from the University of California at Irvine and a postdoctoral degree at the Hebrew University in Jerusalem, both in phage λ genetics, I faced a five-body problem: two careers and three children. Two positions and a family-friendly environment brought us to the Capital District in New York. For me, it was a research scientist position, working on thymidylate synthase (TS). Even in the 1970s, TS was a well studied enzyme, highly regulated in each organism in which it had been studied, and above all, TS was a geneticist's dream: positive selections for both gene function and dysfunction in bacteria. So, I set to work with respected biochemists Frank and Gladys Maley, and almost 30 years ago, we published our first paper together on a single functional arginine involved in TS catalysis (1). This arginine was to reappear on my research radar in a completely different context more than 20 years later. Meanwhile, I developed the TS genetic system for studying the enzyme's function and regulation (2) and taught my colleague Fred Chu how to sequence the TS coding sequence (the td gene) of phage T4. Sequencing was a big deal in those days; entire papers were dedicated to decoding a single gene, and I had taken a week-long course to learn how to sequence DNA. Chu did a superb job, but he presented us with a conundrum. The td gene contained a chunk of sequence that did not correspond to TS. Without the benefit of GenBank™ and BLAST searches, we were left to ponder for ourselves what that intervening sequence might be: an artifact? An intron? But dogma insisted that introns existed only in eukaryotic genes.

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