Mutation patterns of mtDNA: empirical inferences for the coding region.
BACKGROUND
Human mitochondrial DNA (mtDNA) has been extensively used in population and evolutionary genetics studies. Thus, a valid estimate of human mtDNA evolutionary rate is important in many research fields. The small number of estimations performed for the coding region of the molecule, showed important differences between phylogenetic and empirical approaches. We analyzed a portion of the coding region of mtDNA (tRNALeu, ND1 and tRNAIle genes), using individuals belonging to extended families from the Azores Islands (Portugal) with the main aim of providing empirical estimations of the mutation rate of the coding region of mtDNA under different assumptions, and hence to better understand the mtDNA evolutionary process.


RESULTS
Heteroplasmy was detected in 6.5% (3/46) of the families analyzed. In all of the families the presence of mtDNA heteroplasmy resulted from three new point mutations, and no cases of insertions or deletions were identified. Major differences were found in the proportion and type of heteroplasmy found in the genes studied when compared to those obtained in a previous report for the D-loop. Our empirical estimation of mtDNA coding region mutation rate, calculated taking into account the sex of individuals carrying new mutations, the probability of intra-individual fixation of mutations present in heteroplasmy and, to the possible extent, the effect of selection, is similar to that obtained using phylogenetic approaches.


CONCLUSIONS
Based on our results, the discrepancy previously reported between the human mtDNA coding region mutation rates observed along evolutionary timescales and estimations obtained using family pedigrees can be resolved when correcting for the previously cited factors.
Center for Research in Natural Resources (CIRN), University of the Azores, 9500 Ponta Delgada, S, Miguel, Azores, Portugal. cristina.santos@uab.es
Cristina
C
Santos
Rafael
R
Montiel
Adriana
A
Arruda
Luis
L
Alvarez
Maria Pilar
MP
Aluja
Manuela
M
Lima
D001394:Azores; D004272:DNA, Mitochondrial / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D005819:Genetic Markers; D054629:Genome, Mitochondrial; D006239:Haplotypes; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D012355:RNA, Transfer, Ile / Q000235:genetics; D012356:RNA, Transfer, Leu / Q000235:genetics; D017422:Sequence Analysis, DNA
D004272:DNA, Mitochondrial; D005819:Genetic Markers; D012355:RNA, Transfer, Ile; D012356:RNA, Transfer, Leu; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human