A recent update of Adobe Flash Player for Mac made the allele frequency bars shifted to the left. The bars were placed somewhere between two nucleotides, and the hight of the bars did not meet allele frequency data in the info window. The problem has now been corrected. If you use an old version of Flash Player on your Mac, the correction might actually cause a shift to the right. If this is the case, please let me know (along with the version number of your Flash Player), or simply update your Flash Player.

Since this is the first update after three and a half years, I would like to thank to all users of MitoWheel. Special thanks to those who shared their opinion with me or gave some suggestions. Do not give up the hope that Mitowheel 2.0 will come some day (but then without Flash Player)! While waiting, you can read about MitoWheel in the book “The Human Genome – A User’s Guide” by Julia E. Richards and R. Scott Hawley.

The way how the MitoWheel loads at start has been redesigned. On some computers where the loading procedure lasts longer, an error message appeared in previous versions due to time out. (Thanks to nuin for pointing out the problem.) With this update, the Flash Player message should not pop up anymore. In addition, you can also see the progress of the calculations as shown by dots in the search box. If you still have problems loading the MitoWheel, please let me know.

There were small corrections made to the program. However, the most relevant change happened to the web site. I deleted the words ‘Under construction’ in the section ‘How to use’, and I wrote quite a lot of other words instead. Most of the instructions and tricks have been already mentioned here in the blog, but now you can find a more systematic guide right there where the Wheel is. To make the manual more enjoyable, I also included three short videos showing the Wheel in action.

As an appetizer, here you can see the first video about navigating the Wheel. For better quality, check out the original.

1. After a few years of hesitation, I finally switched the orientations of the two replication origins. If you prefer the previous version, or you find some evidence that the previous version was more correct, please let me know.
2. Now you can really spin the Wheel directly! Just click on it and drag it around.

1. MitoWheel incorporates now data on fully sequenced human mitochondrial genomes that have been deposited in the GenBank nucleotide database by different research groups. This means at the moment 2982 complete human mitochondrial DNA sequences. You can type the GenBank accession number into the search field and you will get the list of mutations (positions that are different from the reference sequence). Of course, you can see multiple sequences at the same time (“AY665667, DQ862537″). In this case, the sequences will be distinguished by color. Well, you might ask, who will really search for DQ862537? Probably, you are right… But don’t stop reading!
2. MitoWheel 1.2 is able to show a number of human mitochondrial sequences as a group. In the group view, mutations that occur in any of the sequences in the group are divided into four classes: (a) Mutations that are specific for the group, i. e. they cannot be found in any other known human mtDNA sequence, only in the analysed group. (b) Mutations that are present in all sequences belonging to the group (“ubiquitous“), but also occur outside of the group. (c) Mutations that are missing from some of the sequences, so they define a subgroup within the group. (d) At last, the status of certain sites is shown, although they are identical to the revised Cambridge reference sequence (rCRS). It is necessary, because the reference sequence itself carries some polymorphisms that actually represent a minority within the human population. At such nucleotide positions, where sometimes 98% of the human mtDNA sequences differ from the reference sequence, the lack of the “mutation” is more informative than its presence. For the same reason, rCRS polymorphisms are faded out if they fall into the “ubiquitous” group. Color intensity gives additional information about “specific” and “subgroup” mutations too: those that are carried by many individuals in the group are shown in bright color, while rare ones are faded out. You can also find exact numbers about these features in the info window: next to the name of the mutation, frequency data are shown. The first pair of numbers says how many sequences carry the mutation within the group, and the second pair of number describes how frequent the mutation is in the entire human population.
3. How to create groups of human sequences? By mutations! Select all sequences that carry a certain mutation, or select exactly those that lack it. You just simply have to  type a “+” or a ”-” in front of the name of the mutation. For example, “+4917G, +1888A, -12633A, -930A” means “include sequences that carry 4917G and 1888A, but lack both 12633A and 930A”. This will give a nice little group of 24 sequences with many characteristic mutations (“ubiquitous”), and a dark blue “subgroup” mutation, 11812G, that is missing only from one of the sequences (“23/24″ in the info window). So why don’t you check out that subgroup by typing “+4917G, +1888A, -12633A, -930A, +11812G”? Are you aware that you are doing phylogenetics right now? You landed in a subgroup of the human T2 subclade in haplogroup T.

1. You have already discovered for sure that the MitoWheel is able to show multiple results from any query. You get such multiple results if you type something like “tRNA” or ”AGCTA”. You can then walk through the results by clicking the red arrow in the search field, or simply pressing ENTER over and over. With the  MitoWheel 1.1, we are going one level higher: you can now see several lists of results at the same time. As you might guess from the title of this blog, the different groups of matches are distinguished by color. For example, you can try “complex I, complex III, complex IV, complex V” (as a matter of fact, “c1, c3, c4, c5″ works as well). You will get all the mitochondrially encoded subunits of these protein complexes, each complex in another color. To find out what each color stands for, take a look at the lower left corner. The only rule to make multiple searches is: separate the terms with commas.
2. If your search returns a region that is longer than 30 nucleotides, it will now be shown as an arc.

1. Beside positions, regions, gene names, general terms, or sequence motifs, now you can type into the search field mutations too. What happens is not very different from that when you are searching for a specific position: the wheel moves to the corresponding position. The change is in the info window. If your position is in a protein coding or a tRNA coding region, you will get an additional info on the functional change caused by the mutation. Mutations are accepted in the following forms: 12276A, G12276A, 12276G>A, or if you are a perfectionist m.12276G>A.
2. The results of your queries can be now sent to the clipboard of your operating system. If a search returns a region (i.e. more than just one nucleotide position) a small sign appears in the upper right corner of the info window. If you click on this sign, the sequence will be saved in the clipboard. You can now easily paste it into any other program.

Tipp:  If you more or less found the region on the wheel that you were searching for, and want to make some fine navigation, try the following possibilities:

1. Click on the left or right arrows quickly.
2. Press briefly the left or right buttons on your keyboard.
3. Click on a nucleotide in the sequence bar. This nucleotide will move to the center.