A number of mitochondrial (mt) tRNAs have strong structural
deviations from the classical tRNA cloverleaf secondary
structure and from the conventional L-shaped tertiary structure.
As a consequence, there is a general trend to consider all
mitochondrial tRNAs as “bizarre” tRNAs. Here,
a large sequence comparison of the 22 tRNA genes within 31
fully sequenced mammalian mt genomes has been performed to
define the structural characteristics of this specific group
of tRNAs. Vertical alignments define the degree of
conservation/variability of primary sequences and secondary
structures and search for potential tertiary interactions
within each of the 22 families. Further horizontal alignments
ascertain that, with the exception of serine-specific tRNAs,
mammalian mt tRNAs do fold into cloverleaf structures with
mostly classical features. However, deviations exist and
concern large variations in size of the D- and T-loops. The
predominant absence of the conserved nucleotides G18G19 and
T54T55C56, respectively in these loops, suggests that classical
tertiary interactions between both domains do not take place.
Classification of the tRNA sequences according to their genomic
origin (G-rich or G-poor DNA strand) highlight specific features
such as richness/poorness in mismatches or G-T pairs in stems
and extremely low G-content or C-content in the D- and T-loops.
The resulting 22 “typical” mammalian mitochondrial
sequences built up a phylogenetic basis for experimental structural
and functional investigations. Moreover, they are expected to help
in the evaluation of the possible impacts of those point mutations
detected in human mitochondrial tRNA genes and correlated with
pathologies.