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Referee Comments: Referee 1 (Doron M Behar)

Posted by PLOS_ONE_Group on 17 Mar 2008 at 23:50 GMT

Referee 1's Review (Doron M Behar):

This is an interesting paper that provides a comprehensive revision of all previously reported complete mtDNA sequences from Native Americans as well as providing 14 novel sequences. By doing so, the paper provides an up-to-dated phylogeny of the four Pan-American clades, allows the estimation of the number of the Beringian founders, and sets the needed framework for future phylogenetic studies in the subject. In addition, the paper just fully corrects inaccuracies in the medical knowledge accumulated in the literature with respect to the potential causative role of mtDNA mutations in some diseases affecting the discussed population. Therefore, I find the paper of interest to the wide audience as well as to mtDNA experts both in the fields of population and medical genetics. I am listing below my few comments for the authors to consider:

1. Page 1, line 8 of abstract: "suggest that only six haplotypes might have been present in the Beringian founders": - I am not sure that this claim can be made. I would feel more comfortable with a claim that regards the survival to present day of only six haplotypes as there is no real way to estimate the number of extinct maternal founders.

2. Page 2: The authors use the word Eskimos - to my knowledge in some parts of North America the term might be offensive.

3. Page 3: A2 phylogeny - The labeling A2a and A2b are concordant with Tamm 2007 and Derenko 2007. However there is some confusion with the labeling of A2a and Tanaka 2004. It actually seems that Tanaka A2a shares 11365 with A2b as presented herein, Tamm and Derenko. As this recycling of the label was not discussed it will be important to do so and avoid future confusion.

4. Clock: the timing and coalescence analysis leading to the conclusions in this paper strongly depend on the specific calibration and estimation used. At a lack of final resolution between the approach taken herein and the one taken by Tamm 2007, I find it hard to have a final understanding regarding the migration process to the Americas. It is important that the two models, one suggesting that Native American's founder took a break in the Beringia, and the second presented hetrein will be visible. The authors might consider including 1-2 sentences highlighting this issue and the need to work towards a consensus in the "clock" issue.

5. Discussion: first paragraph: in continuum to point one above: there is a need to emphasis that the real number of maternal founders in Beringia can not be estimated from the analysis presented in this paper. Only the number of maternal lineages surviving to our days should be discussed.

N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.