BMC Genomics 2008, 9:122 http://www.biomedcentral.com/1471-2164/9/122 FMiagturerseh4ka distribution Matreshka distribution. Five parameters are displayed: matreshka amino acid length (x-axis), the number of positions where a stop codon could have interrupted the matreshka (y-axis), presence of tandem repeats (matreshkas with no measured tan- dem repeats in any species are in white, matreshkas with tandem repeats in any species are in grey), whether the matreshka starts with any amino acid (circles) or with methionine only (triangles), and whether the probability of matreshka truncation by a stop codon is lower (small shapes) or higher (large shapes) than 0.999. The most interesting candidates are the longest matreshkas with the highest number of possible stop positions, and with no measured tandem repeats (black). An important indication, however, that the THPO matreshkaM may be translated not from a leaky scanning event, but instead as part of a frameshifted splice variant, came from a BLAST search of the matreshkaM against the UniProt protein database [18]. A 100% identity match was found against the translation of the 'nirs' THPO splice variant. No function specific to the nirs THPO appears to be documented. This variant contains a frameshift down- stream of the matreshkaM start, which effectively places the 3' half of the transcript in the same frame as the matreshkaM (Fig. 6C). A SNP [19] exists which can generate a stop codon in (and thus truncate) the matreshkaM at the 45th amino acid (Fig. 6A). The SNP replaces a glycine with a glutamate at posi- tion 116 in THPO itself, on a loop between an alpha-helix and a beta sheet. Gly116 is within the conserved, 184aa long Erythropoietin-Thrombopoietin domain in the N- terminal portion of THPO. This domain is responsible for Page 8 of 16 (page number not for citation purposes)