Can the occurrence of rare insertion/deletion polymor-phisms in human mtDNA be verified from phylogeny?

Owing to its maternal inheritance, absence of re-combination and high evolution rate, mtDNA has been widely used in unraveling the migration history of modern human and in medical genetics as well as in forensic prac-tice1,2]. Compared with the Cambridge reference sequence (CRS) which was first sequenced in 19813] and the later revised CRS4], insertions and deletions (indel) occur fre-quently in the mtDNA sequences available. Some of the indel polymorphisms are characteristic to mtDNA…

Can the occurrence of rare insertion/deletion polymor-phisms in human mtDNA beverified from phylogeny?

Due to its specific characteristics, such as ma-ternal inheritance and absence of recombination, each mtDNA belongs to certain monophyletic clade in the rooted mtDNA tree (haplogroup) according to the mutations it harbors. Rare mutation (excluding parallel mutation) occur-ring at multiple times in different haplogroups could thus be a potential reading error according to the mtDNA phylogeny. This experience has been widely used in double-checking the credibility of the rare mutations in human mtDNA sequences. However, no test has been performed so far for the feasibility of applying this strategy to the rare insertion/deletion (indel) events in mtDNA sequences. In this study, we attempted to relate the rare indels in mtDNAs to their haplogroup status in a total of 2352 individuals from 50 populations in China. Our results show that the insertion of A at position 16259 is restricted to a subclade of haplogroup C and can be verified. The other indel polymorphisms, which occur in the repeat of the deleted or inserted nucleotide(s), may not be distin-guished from phantom mutations from a phylogenetic point of view. Independently and multiply sequencing the frag-ment with the indel is the best and the most reliable way for confirmation.