The estimated ages (18–24 ky) of the four pan-American haplogroups A2, B2, C1, and D1 are quite similar with an average value of 20 ky. Thus, if A2, B2, C1, and D1 entered the Americas without variation in the coding region – in other words, each with only a single (successful) founder sequence (the root haplotype), their entry into the Americas would have occurred right after the peak of the Last Glacial Maximum (LGM, centered at ~21.0 kya and extending from 19.0 to at least 23.0 kya 
), or slightly earlier, so that a coastal (Pacific) route would have been the only option during such glacial periods. On the other hand, it is quite plausible that some intra-haplogroup variation – hardly noticeable at the level of HVS-I motifs – already existed in Beringia and was carried directly further south into the American double-continent. If one assumes that at least the root haplotypes of A2, B2, D1, as well as of C1b, C1c, and C1d were of Beringian origin, then the entry time would come slightly down (19.0 kya), that is, falling exactly at the end of the LGM. Moreover, the relatively lower coalescence time (~17 ky) of the entire haplogroup A2 () – including the shared sub-arctic branches A2b (Siberians and Inuits) and A2a (Siberians, Inuits and Na-Dené) 
– is probably due to secondary expansions of haplogroup A2 from Beringia long after the end of the LGM, which would have averaged the overall internal variation of haplogroup A2 in North America – the main source of the A2 mtDNAs in this study.
In any case, all the abovementioned scenarios do not support the ‘Clovis-first’ hypothesis, but are well in agreement with the undisputed ages of the earliest Paleoindians in South America 
. This conclusion would not change if one adopted the effectively faster rate of Kivisild et al. 
based only on synonymous substitutions, which would generally shrink ages by a factor of ~3/4, as judged from a comparison with both the ages of the Native American haplogroups 
and those of super-haplogroups L, L3, M, and N 
. Therefore the main difference between both rates seems to concern only the absolute calibration as manifested in the estimated global coalescence times for super-haplogroup L. It is dubious whether the partial utilization of the coding-region information 
leads to more credible age estimates, taking into account the extremely low amount of synonymous mutation data characterizing younger clades, such as the Amerindian ones, and the extreme discrepancies with ages based on control-region variation of some haplogroups such as H, I, T, and U5 
. Moreover, if as suggested 
, the molecular clock did not apply to the entire coding region, but only to the synonymous mutations in the 13 genes coding for protein subunits, it would be rather unlikely that an age overlapping such as that reported for the well represented founder haplogroups (A2, B2, D1, C1b, and C1c) in would be observed. In any case, with both clocks, a Beringian stage preceeding the expansion into the Americas – estimated at slightly different starting times and with a different duration depending on the clock employed – most likely took place, thus explaining the differentiation of the pan-American lineages from the Asian sister-clades ().
Our snapshot of the phylogenies for haplogroups A2, B2, C1, and D1 is only partially representative of Native American mtDNA variation, since most likely it only marginally includes the variation of Native American populations from Central and South America. However, despite this limitation, it is clear that one has to anticipate a pronounced starlike pattern near the root of each respective founder haplogroup/branch. The starlike pattern enhances the precision of the dating of the human entry into the Americas, but inevitably hinges upon the calibration employed and, perhaps more importantly, on a detailed founder analysis across the double-continent. Therefore it will require major sampling and sequencing efforts in the future for uncovering all of the most basal variation in the Native American mtDNA haplogroups by targeting, if possible, both the general mixed population of national states and autochthonous Native American groups, especially in Central and South America.
A widespread knowledge of the specifics for the Native American haplogroups can also prevent the publishing of effectively mutilated or distorted mtDNA sequences from complete sequencing efforts in clinical studies 
, but most importantly, the dissection of pan-American haplogroups into clades of younger age and more limited geographic and ethnic distributions is essential for reliable association studies between mtDNA haplogroups and complex disorders