{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:45:52Z","timestamp":1773665152988,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Summary: Central to the unraveling of the early evolution of the genome is the origin and role of introns. The evolution of the genome can be characterized by a continuous expansion of functional modules that occurs without the interruption of existing processes. The design-by-contract methodology of software development offers a modular approach to design that seeks to increase flexibility by focusing on the design of constant interfaces between functional modules. Here, it is shown that design-by-contract can offer a framework for genome evolution. The definition of an ancient exon module with identical splice sites leads to a relatively simple sequence of events that explains the role of introns, intron phase differences and the evolution of multi-exon proteins in an RNA world. An interaction of the experimentally defined six-nucleotide splicing consensus sequence together with a limited number of primitive ribozymes can account for a rapid creation of protein diversity.<\/jats:p>\n               <jats:p>Contact: \u00a0albert.de.roos@thebeaglearmada.nl<\/jats:p>","DOI":"10.1093\/bioinformatics\/bth475","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T00:15:36Z","timestamp":1092356136000},"page":"2-9","source":"Crossref","is-referenced-by-count":12,"title":["Origins of introns based on the definition of exon modules and their conserved interfaces"],"prefix":"10.1093","volume":"21","author":[{"given":"Albert D. 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