Asymmetrical directional mutation pressure in the mitochondrial genome of mammals

Abstract

The base composition of 25 complete mammalian mitochondrial (mt) genomes has been analyzed taking into account all three codon positions (P1230 and fourfold degenerate sites (P4FD) of H-strand genes. In the nontranscribed L strand, G is the less represented base and A is the most represented one in all cases, while C and T differ among species. H-strand protein-coding genes show an asymmetric distribution of the four bases between the two strands. The asymmetry indexes AT and GC skews on P4FD are much higher than those on P123, suggesting the existence of asymmetrical directional mutation pressure. Relationships between the compositional features and transcription of replication processes have been investigated in order to find a possible mechanism that could explain the origin of this asymmetry. AT and GC skews, the base composition in fourfold degenerate sites, and the number of variable sites for each gene are significantly correlated with the duration of single-stranded state of the H-stranded genes during replication. We tested 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 results, hydrolytic deaminations being the only one in agreement with our data. Thus, we hypothesize that one of the crucial processes for the origin of asymmetric and biased base composition of mammalian mitochondrial genomes is the spontaneous deamination of C and A in the H strand during replication.

The Response of Amino Acid Frequencies to Directional Mutation Pressure in Mitochondrial Genome Sequences Is Related to the Physical Properties of the Amino Acids and to the Structure of the Genetic Code

“…All these lines have slopes significantly different from zero (p< 0.001 for U and C, p < 0.005 for G, p < 0.01 for A). This confirms that there is a significant variation in the mutational process along the genome, as has already been seen (Reyes et al 1998;Faith & Pollock, 2003;Gibson et al 2005). Following the arguments given in the main part of this paper, we would expect this to cause a corresponding variation in frequencies at 1 st and 2 nd positions, i.e.…”

“…A quantity D ssH has been proposed as a measure of the amount of time a gene is single stranded (Reyes et al 1998;Faith & Pollock, 2003). If mutations occurring in the single stranded state are responsible for the asymmetry of the mutation process, we would expect base frequencies to vary along the genome according to the amount of time spent single stranded.…”

“…If mutations occurring in the single stranded state are responsible for the asymmetry of the mutation process, we would expect base frequencies to vary along the genome according to the amount of time spent single stranded. In fact, base frequencies in individual genes are found to correlate with D ssH (Reyes et al 1998;Faith & Pollock, 2003;Gibson et al In a phylogenetic context, maximum likelihood models have also been developed that incorporate strand asymmetry (Bielawski & Gold, 2002;Krishnan et al 2004). Raina et al (2005) have also shown that strand asymmetry at 1 st and 2 nd positions is related to that at FFD sites in a maximum likelihood phylogenetic study of primates.…”

“…These frequencies are shown in Figure 12. The genes are ranked in order of increasing D ssH (following Reyes et al 1998). …”

Genetic aspects of mitochondrial genome evolution

“…Since this difference is physically measurable (Anderson et al, 1981) the G rich strand is also termed heavy strand (H-strand) and the other light strand (L-strand). In particular one strand of mammalian mitogenomes has been reported to be GT rich (Reyes et al, 1998). In contrast (both strands) of the mitogenomes of Arthropoda are AT rich (Crease, 1999).…”