Thursday, 21 February 2008

dna - Why did high A+T content create problems for the Plasmodium falciparum genome project?

The main paper for the Plasmodium palciparum genome project (Gardner et al., 2002) repeatedly mentioned that the unusually high A+T content (~80%) of the genome caused problems. For example they imply that it prevented them using a clone-by-clone approach:




Also, high-quality large insert libraries of (A + T)-rich P. falciparum DNA have never been constructed in Escherichia coli, which ruled out a clone-by-clone sequencing strategy.




And that it made gene annotation difficult:




The origin of many candidate organelle-derived genes could not be conclusively determined, in part due to the problems inherent in analysing genes of very high (A + T) content.




Question:
What is the biological significance of high A+T content, and why would it cause problems in genome sequencing?



Ref:
Gardner, M.J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R.W., Carlton, J.M., Pain, A., Nelson, K.E., Bowman, S., Paulsen, I.T., James, K., Eisen, J.A., Rutherford, K., et al. (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 419 (6906), 498–511.

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