The establishing of the complete genome sequence of the first animal, C. elegans had been preceded by a two-decade long thoughtful phenotypic and genetic analysis of the organism. As a consequence, from the sequence information we could go back to the biology, and vice versa. We believed that the genomic information from the model organism C. elegans would ease to explore the biology of other nematodes, like the entomopathogenic Heterorhabditis and Steinernema species. It was hoped that if we determine the genomic sequences of these nematodes and compare them scientifically with that of C. elegans it will help to explore the differences and similarities at the level of the organisms. Although the genome of H. bacteriophora has been sequenced by a large consortium and was compared professionally to that of C. elegans, it may not replace the thoughtful genetic analysis of that species. There are some conclusions that could not be drawn simply from the sequence information without a functional aspect. Let me provide two examples of unsolved problems which might not been over-bridged by the comparative sequence analysis.
- Thank for the thoughtful genetic analysis of the Riddle laboratory, the genetic pathway of dauer-larva formation and recovery in C. elegans is well known. The dauer stage is of a vital importance for entomopathogenic nematodes. Surprisingly enough, there are hardly any genes related to C. elegans daf (C) and daf (def) genes were found in H. bacteriophora. Despite the sequence information, the genetic analysis of the dauerlarva formation and recovery in H. bacteriophora cannot be avoided.
- Thank for the pioneer work followed by a thoughtful genetic analysis at the highest intellectual level of the forth member of the three-member Nobel- laureate team, Jonathan Hodgkin, the sex determination and dosage compensation in C. elegans is completely known. Disappointingly, hardly any of the genes of playing key role in these processes could be found in the H. bacteriophora genome.
Both examples indicate that similar biological problems could be solved by different genes in closely related species. The classical genetic analysis of biological functions cannot exclusively be replaced by the sequence analysis. In the absence of the proper classical genetic information the road from sequence to biology is only a one-way street with a dead end.
References
Adhikari BN, Lin CY, Bai X, Ciche TA, Grewal PS, Dillman AR, Chaston JM, Shapiro-Ilan DI, Bilgrami AL, Gaugler R, Sternberg PW, and Adams BJ. (2009). Transcriptional profiling of trait deterioration in the insect pathogenic nematode Heterorhabditis bacteriophora. BMC Genomics. 10:609. 
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