ASYMMETRICAL DIRECTIONAL MUTATION PRESSURE IN THE MITOCHONDRIAL GENOME OF MAMMALS

The base composition of 25 complete mammalian mitochondrial (mt) genom es has been analyzed taking into account all three codon positions (P- 123) and fourfold degenerate sites (P-4FD) of H-strand genes. In the n ontranscribed L strand, G is the less represented base and A is the mo st represented one in all cases, while C and T differ among species. H -strand protein-coding genes show an asymmetric distribution of the fo ur bases between the two strands. The asymmetry indexes AT and GC skew s on P-4FD are much higher than those on P-123, suggesting the existen ce of asymmetrical directional mutation pressure. Relationships betwee n the compositional features and transcription or replication processe s have been investigated in order to find a possible mechanism that co uld explain the origin of this asymmetry. AT and GC skews, the base co mposition in fourfold degenerate sites, and the number of variable sit es for each gene are significantly correlated with the duration of sin gle-stranded state of the H-stranded genes during replication. We test ed different replication-related hypotheses, such as the existence of biased dNTP pools, gamma DNA polymerase mispairing, and the asymmetric replication itself. Most of them failed to explain the observed resul ts, hydrolytic deaminations being the only one in agreement with our d ata. Thus, we hypothesize that one of the crucial processes for the or igin of asymmetric and biased base composition of mammalian mitochondr ial genomes is the spontaneous deamination of C and A in the H strand during replication.