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