Entering edit mode
6.9 years ago
Zar
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0
For my undergraduate project, we were interested in finding out why Atlantic killifish from a polluted site were resistant to PCBs while fish from a reference site were sensitive. We hypothesized that PCBs interfered with the interaction between two proteins, RYR and FKBP12, at specific residues. However, sequencing results showed no mutation in any of the selected residues. I decided to use dbSNP and filtered for SNPs involving the RYR-FKBP12 interaction and found no such SNPs as well. Would it be correct to assume that the sequences involved in the interaction are conserved?
What was the reasoning behind that hypothesis? Is PCB known to do that?
Yeah, certain PCBs enhanced the activity of different RYR isoforms.
Your observations are in line with the findings of this paper which seems to indicate that the differences may be due to increased gene expression (through altered regulation perhaps?)
Since you did not find any SNP's in the regions that code for the interacting residues on those proteins those regions are potentially under selection pressure.
Assuming all the unknown details of your experimental set up are correct (good sample size, proper sequencing, possibly known phenotype of the individuals genotyped, etc), even then it would be risky to assume the sequences are conserved.
How can you rule out alternative explanations, like a huge bottleneck, or a selective sweep?