Proteins 2003;53:241–251.
© 2003 Wiley-Liss, Inc.
Analysis of Singleton ORFans in Fully Sequenced Microbial Genomes
Naomi Siew1,2 and Daniel Fischer2*
1Department of Chemistry, Ben Gurion University, Beer-Sheva, Israel
2Bioinformatics Group, Department of Computer Science, Ben Gurion University, Beer-Sheva, Israel
ABSTRACT
Singleton sequence ORFans are orphan ORFs (open reading frames) that have no detectable sequence similarity to any other sequence in the databases. ORFans are of particular interest not only as evolutionary puzzles but also because we can learn little about them using bioinformatics tools. Here, we present a first systematic analysis of singleton ORFans in the first 60 fully sequenced microbial genomes. We show that although ORFans have been underemphasized, the number of ORFans is steadily growing, currently accounting for 23,634 sequences. At the same time, the percentage of ORFans as a fraction of all sequences is slowly diminishing, and is currently about 14%. Short ORFans comprise about 61% of all ORFans. The abundance of short ORFans may be due to a yet unexplained artifact. The data also suggest that the number of longer ORFans may soon diminish as more genomes of closely related organisms become available. To better address the questions about the functions and origins of ORFans, we propose to focus further studies on the longer ORFans, with emphasis on three new types of ORFans: ORFan modules, paralogous ORFans, and orthologous ORFans. We conclude that the large number of ORFans reflects an intrinsic property of the genetic material not yet fully understood. Further computational and experimental studies aimed at understanding Nature’s protein diversity should also include ORFans.
Key words: ORFans; complete genomes; evolution; singletons; microbial diversity
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EXCERPT/EXCERTO:
If evolution works through descent with modification, then why is it that no similar sequences are found in other organisms? Why is it that we do not find today any of the necessary “intermediate sequences” that must have given rise to these ORFans? Is the origin of these highly divergent sequences due to massive gene loss, or to a process of rapid evolution? 13,17,18
Although ORFans entail interesting evolutionary puzzles and comprise a significant portion of the genetic material, they have not received proportional attention from the scientific community, and calls for “affirmative action” for ORFans have been suggested. 3
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