Investigating Evolutionary Pressures on Protein Sequence: Applications to Drug Resistance in Flatworm Parasites

Abstract

Abstract: The aim of This report is that it focuses on a particular flatworm called S mansoni and the disease it causes in humans and cattle, called schistosomiasis. This disease causes a million deaths annually across the globe. The drug for this disease is praziquantel, which is quite effective. Though lately, S mansoni is showing resistance towards this drug. In particular, The aim of this project is to find the regions showing evolutionary pressure in its protein structure and, hence, know how the protein structure mutates. The methods used in this project, amongst others, are SNAP, rasmol, clustal omega mainly. They are supported by using fundamentals from PDB, Biomart, blast. These methods are very helpful to biologists or people with less programming experience. This report will explore each method in detail before using them, and the steps needed to properly execute them are discussed as well. Along with the methods, this will use raw data in the form of protein sequence/ FASTA sequence from biomart. For the results, 12 different types of flatworms are chosen but narrowed down to 3-4, which closely resemble the structure of S mansoni. These flatworms are combined into a multiple sequence alignment. They are later compared using SNAP tool. Using the data from SNAP, the dn/ds ratio for each codon number is computed and the type of selection is determined. {dn/ds ratio and selection type are defined in further sections} For discussion and conclusion, the selection type, if positive, shows evolutionary pressure and the protein structure mutates and discusses its inference. It is shown visually through RASMOL tool. This tool helps in locating the binding sites where mutation takes place, so, focusing on those will help future researchers in finding a universal vaccine for this and some other viruses as well. The main finding of this experiment is the detection of regions of positive selection in the protein structure of the flatworm, using dn/ds. Also, the amino acid residues are explored as well. As with every experiment, this report covers the limitations of the process and the future works being carried on. The referencing style is APA Harvard, and the appendix section covers all the raw data used.