Revathi Rajkumar; Jheelam Banerjee; Hima Bindu Gunturi; R Trivedi; VK Kashyap

“ While some authors have suggested a southwest Asian origin of M macrohaplogroup, followed by a back migration to Africa [ [5] , others support its African ancestry [ [11] . One major drawback in arriving to a conclusion is the limitation of control region sequences in providing reliable estimate of phylogeny owing to homoplasy and recurrent mutations [ [9] , [12] .
Complete mitochondrial genome sequencing has gained importance in resolving phylogenies and understanding human evolution. ”

“ Since M macrohaplogroup is derived from L3, which finds its roots in East Africa, it is believed that presence of M1 in Ethiopia further substantiates an African origin of M. A similar hypothesis had been drawn for the U6 lineage that is autochthonous to North Africa although U haplogroup displays its maximum diversity in Near East [20] . The authors of this study prepared an in-depth phylogeography of U6 to infer a back migration of this lineage from West Asia to North Africa. ”

“ However, more M2b genomes need to be completely sequenced before reaching this conclusion and though HVSI sequences are not very reliable for constructing phylogenies, this cluster can well differentiate individuals with only one or both mutations and in turn resolve the phylogeny to its finer sub-lineages. M2 lineage is the oldest M lineage found in India with an estimated age of approximately 50,000 YBP, using only coding region motifs estimation, opposed to the expansion date of 60,000–75,000 yrs calculated from control region sequence information [ [5] . ”

“ The M2 genome and its sub-lineages, more specifically M2a, have been well described in Indian population. Nevertheless complete sequencing of M2a demonstrated the presence of a novel site T9758C, which is characterized as a diagnostic marker for M2a sub-lineage, in addition to the previous reported, G5252A and A8396G transitions [ [5] . This finding reinforces the importance of sequencing a large number of individuals belonging to a lineage for describing a detailed phylogeny. The study was unable to trace any specific marker for M2b sub-lineage. ”

“ The deep roots of M phylogeny clearly establish the antiquity of Indian lineages, especially M2, as compared to Ethiopian M1 lineage and hence, support an Asian origin of M majorhaplogroup.
Background
During the last few years a surge in information on mitochondrial DNA control region sequence has been observed along with information from coding region substitutions in diverse populations of the world to understand their genetic diversity, structuring and origins [1] - [2] . ”

“ The M phylogenetic tree constructed on whole mt sequence information of twenty four samples belonging to different M lineages and their sub-types including M1, M2, M2a, M2b, M30, M30a, M18, M*, M3, M4, M5, M6, and M25 is provided in Figure 1.
Phylogenetic tree of M macrohaplogroup based on complete mt DNA genome sequences. Numbers along links refer to substitutions at nucleotide positions with respect to rCRS. Suffixes are transversions. Grey colour represents potential new lineage. Asterisk denotes unclassified lineage. ”

“ With the exception of the M1 lineage that is confined to Ethiopia [ [7] , all the other branches of this macrohaplogroup including M*, C, D, G, E and Z haplogroups are observed in Asia [ [3] , [8] , [9] , [10] . The lineages M2, M3, M4, M5, M6, M18 and M25 are exclusive to India, with M2 reported to be the most ancient lineage in the sub-continent with an age estimation of 60,000 yrs-75,000 yrs. ”

“ This site was nevertheless absent in the other two samples, one of which had a similar HVSI motif as M5a mt DNA genome, while the other exhibited an additional site G16048A in its control region motif. Our study identifies a transversion at C10986A, shared by all the three samples, suggesting that these sequence types branched out from a common root. Analysis of C10986A substitution in seven Indian samples possessing HVSI motif, G16048A, G16129A and C16223T, confirms our finding that different branches emerged from M5 lineage. ”

“ A total of eighteen Indian individuals belonged to M30a lineage. Three mt DNA genomes further branched out from M30 lineage, possessing only G12007A substitution. Interestingly, the newly described M18 (C16223, A16318T) matriline is one of the branches that directly emerged from M30 lineage. Sequence analysis of ten M18 mt DNA genomes showed the presence of G12007A transition. Eighteen Indian individuals were identified from our mtDNA database as possessing a HVSI motif (C16223T, A16300G) similar to the Saora sample, which arose as an offshoot of M30 lineage. ”

“ Presence of T12477C transition in only one of the two M5 mt DNA genomes sharing an identical HVSI motif, C16223T and G16129A, further substantiates the importance of coding region markers in precisely identifying mitochondrial phylogenies. ”