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Download Ivy Mead 24 February 2011 Bioinformatics Lab report 3 The analysis
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Ivy Mead 24 February 2011 Bioinformatics Lab report 3 The analysis for Telomerase Reverse Transcriptase (TERT) has been done at the protein level because the evaluation can provide a more clear distinction between those kind of sequences. Because transcriptase is such an important protein for maintaining DNA quality, it is less likely to change in monumental ways, at least in the mammalian structures. The ciliate and yeast sequences are expected to be more different from the mammalian sequences because of the longer time since divergence. Looking for important differences can be better done at the protein level by avoiding problems with synonymous DNA mutation and that only 4 exchange values versus 20 amino acid residues for exchange. The analysis for Telomerase RNA Component (TERC) has been done at the nucleotide level because it is never translated into a protein. For the TERT, the parameter of gap opening penalty is increased in anticipation that the most of the sequences will be similar, because the protein is likely conserved. By increasing the gap opening penalty, the program is more discriminate and provides a more stringent criteria for the sequence alignment. Thus, the active sites of the protein should be easily found. For the TERC the default SWAMI gap opening penalty has been used because the sequences are likely less closely related for reasons stated in the former paragraph. A middle range alignment is best for a component that is more likely to differ, although the standard should not be so low as to not align the binding site. It is also important to note that the default gap penalty is not ideal for all sequence alignments; it should only be used as a baseline and with caution. The two components of telomerase can be quantitatively compared using alignment scores. The alignment score for TERT was found to be 103905 and the alignment score for TERC was found to be 67033. Thus, when comparing the two components with the alignment score as the standard the TERC appears to be evolving more quickly because on average the sequences are less closely aligned. Because the TERT alignment has a higher alignment score, there are fewer mutations between sequences, even those that are not as recently related appear to have fixed less mutations than the TERC sequences. Thus, it is highly likely that the TERC sequence is fixing mutations at a higher rate than the TERT protein sequence. The functional domain in TERC is approximately from 197 to 377 nucleotides in the mammalian sequences. The two functional domains are approximately from 1473 to 2184 nucleotides and 2289 to 3153 nucleotides in the mammalian sequences. These were estimated by looking for areas that were particularly conserved among a majority of the organisms selected. The yeast and the ciliate sequences were significantly different from the mammalian sequences even in the functional domains, but that is to be expected as they are less closely related and have had more evolutionary time to diverge in sequence. Thus, it would be safe to assume that the yeast and ciliate homologs of TERC and TERC have functional similarity but not evolutionary similarity or structural similarity to the mammalian versions. Paralogs of TERT exactly do not appear to exist that we know of; however, a paralog of the yeast EST1 (a third component of the ribonucleoprotein telomerase complex) has been found in humans called EST1A, which can affect telomere capping (Reichenbach et al., 2003). Another study found a possible paralog in the Melanoma antigen family (MAGE) (Amin et al., 2009). Paralogs of TERC are unlikely to occur unless they end up evolving alongside TERT, no literature on the subject has been found. Works Cited: Amin, et al., (2009) In silico Analysis of Human Telomerase Reverse Transcriptase (hTERT) Gene: Identification of a Distant Homolog of Melanoma Antigen Family Gene (MAGE). Cancer Inform. 7: 171–181. Reichenbach, et al., (2003) A Human Homolog of Yeast Est1 Associates with Telomerase and Uncaps Chromosome Ends When Overexpressed. Current Bio. 13: 568-574.