BMC Genomics 2005, 6:136 http://www.biomedcentral.com/1471-2164/6/136 PFyigriumriedi6ne-purine codon position walks of human mtDNA-encoded protein transcripts Pyrimidine-purine codon position walks of human mtDNA-encoded protein transcripts. The COX1 transcript walk, absent in this figure, is shown in Figure 5A. All 13 genes have similar patterns in the codon positions of the pyrimidine- purine walks. Discussion Mitochondrial-encoded membrane protein transcripts are pyrimidine-rich Protein transcripts with an abundance of U (T) in the sec- ond codon position encode hydrophobic amino acids [10,13] that tend to form membrane-spanning alpha hel- ices [14] or beta strands [12]. This is likely the most important factor that contributes to the relative pyrimi- dine-richness of mitochondrial membrane complex transcripts. However it does not explain the entire signal in humans where large quantities of C in the third codon position also play an important role. In fact, the pyrimi- dine-rich signal in humans is mainly driven by C in the third codon position (Table 2). The signal is also partially driven by the lack of G in the transcripts. Mitochondrial DNA is replicated by a strand asymmetric mechanism [15] that is likely responsible for the unequal strand distribu- tion of G nucleotides [16]. G is the most easily oxidized base, forming 8-hydroxy guanine [17]. A low percentage of G in the vertebrate mitochondrial transcripts has been hypothesized to contribute to mRNA stability in the oxi- dative environment of the matrix space [18]. However, we must emphasize that the low G abundance in the light strand in vertebrates is not the primary source of the pyri- midine richness in these transcripts, because membrane protein transcripts are also pyrimidine-rich in species where no mitochondrial strand asymmetry in G content is present (see Table 2). Page 10 of 12 (page number not for citation purposes)