BMC Genomics 2006, 7:282 http://www.biomedcentral.com/1471-2164/7/282 ORFs containing MGE domains were identified in the genome in three ways: i) a HMMER search using Pfam_fs HMMs ii) a BLASTP search using the RT consensus sequence developed in this study, and iii) a BLASTP search using the P. y. yoelii and P. falciparum MGE domain sequences identified from InterPro but not located in Pfam. Only the Pfam entries with significant hits are listed. Number of ORFs E values and/or sequence alignment scores 2 1 23 1 1 2 10 E values -9 and -10 Scores 37 and 39 E value -8 Score 35.5 E values -8 to -27 Scores 35 to 104 E value -13 Score 52 E value -3 Score 21 E values -2 and -3 E values -4 to -168 Table 2: P. vivax ORFs containing MGE domains. Pfam entry PF03184 Endonuclease CENP-B protein PF00692 DeoxyUTP pyrophosphatase PF00078 Reverse transcriptase PF00589 phage integrase catalytic domain PF07460 Intron-encoded nuclease 2 Similarity to RT sequence developed in this study Determined by BLASTP search Similarity to P. y. yoelii and P. falciparum ORFs not in Pfam Determined by BLASTP search identity to ORFs in the M. musculus genome and were rejected from the data as being contaminating sequences. These were PY06984, PY07613, PY07841, PY07669, PY07288, PY06363 and PY07014. The fact that these ORFs have homologues in other rodents e.g. Rattus nor- vegicus, confirms they are contaminating sequences. MGEs and the P. falciparum genome Given the above limitations and that the evidence pre- sented here would need to be confirmed experimentally, these findings raise some interesting questions. While there are potentially several MGEs of different classes in P. y. yoelii and P. vivax, P. falciparum appears to contain very few. MGEs are ubiquitous in nature and are considered important catalysts for genome evolution. An interesting exception is the fungal genus Neurospora, which has the widest array of genome defence mechanisms found in eukaryotes, including the repeat-induced point mutation (RIP) mechanism whereby cytidine is mutated to thymi- dine [20,21]. This has had a profound impact on the organism's genome: it has extinguished active MGEs and driven the genome to become AT-rich, particularly in the non-coding regions [22]. Since the discovery of RIP- induced MGE silencing in Neurospora, this mechanism has been demonstrated in all kingdoms of life. Most recently, Kuhlmann et al have demonstrated that a RIP-like mecha- nism is capable of silencing retrotransposons in Dictyostel- ium [23]. This not only extinguishes MGE activity, but drives the AT bias in repeated sequences by subsequent deamination of methylated cytidine residues. These two features – an AT-rich genome (increasing to ~90% in non- coding regions) and an apparent lack of active MGEs – are notable features of P. falciparum. In addition, two putative DNA methyltransferases (PF11_0284 and PF13_0286) and a putative cytidine deaminase (PF13_0259) have been identified in P. falciparum, suggesting that the poten- tial exists for methylation and deamination of cytidine residues in the genome. The evolutionary forces that drive genomes to become compositionally biased are complex and largely theoreti- cal. The arguments put forward depend upon the ecologi- cal niche of the individual organism and proposed hypotheses are therefore species specific. No hypothesis has been forthcoming for the AT richness found in P. fal- ciparum. Since the initial effect of MGE invasion on the host genome is almost always negative [4], a selective pressure would exist to minimize MGE activity. Based on the data presented in this study, we propose the following two hypotheses, both of which may offer an evolutionary explanation for part of the AT richness of the P. falciparum genome: i) A genome protective mechanism, such as the RIP- induced silencing of transposable elements, has been a potential driving force behind the compositional bias of the P. falciparum genome. ii) The AT-rich genome of P. falciparum has been selected for as a result of its inherent resistance to MGE invasion. Page 7 of 10 (page number not for citation purposes)