Population genetics and anticoagulant resistance of Rattus tiomanicus in oil palm plantation inferred from VKORC1 gene mutations / Mohamad Harris Nasir

Mohamad Harris , Nasir (2022) Population genetics and anticoagulant resistance of Rattus tiomanicus in oil palm plantation inferred from VKORC1 gene mutations / Mohamad Harris Nasir. PhD thesis, Universiti Malaya.

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Abstract

Rat of the Rattus species is the main group identified as pests in oil palm plantation in Malaysia. The constant use of anticoagulant rodenticides (ARs) for rat control in oil palm plantations exert selective pressure on Vitamin K epOxide Reductase Complex subunit 1 (VKORC1), potentially resulting in rodenticide resistance. The aims of this study were to determine Rattus species diversity by using genetic tools and to characterize the dominant species population structure. In addition, the resistance region of VKORC1 gene in the population of Rattus species and assess the impact to the rodenticides efficacy rate were investigated. Rats from five oil palm plantations in Peninsular Malaysia were trapped from 2018-2019 and morphologically identified. COI sequences extracted from the rat liver tissue were used for molecular identification based on DNA barcoding and population structure analysis. The VKORC1 gene was screened for mutations using MEGA X software, and the mutated residue’s structure was visualized using the I-TASSER platform. Molecular docking using Chimera software were also used to predict the favoured interaction between the mutated protein structure and the ARs active compound to support a possible AR resistance. A total of 341 COI sequences of rats were used for the species identification. Based on DNA barcoding analysis and phylogenetic analysis, R. tiomanicus was the most abundance in our study sites with highest diversity index (H’= 1.31) compared with other species; R. argentiventer, R. rattus diardi, R. exulans and R. tanezumi. The most abundance, R. tiomanicus has been chosen for the population structure study and VKORC1 screening. In this study, a pattern of isolation by distance was detected in R. tiomanicus populations, suggesting an unlikely event of inbreeding and migration with no recent event of population pattern expansion and low gene flow between populations (FST= 0.045, p>0.001). Thus, population migration is not a risk factor in eradication effort. Screening on the R. tiomanicus VKORC1 gene resulted in identification of four mutated foci on residue Gly64Ala, Gly64Val, Leu65Pro and Glu67Ala in Exon 2 that led to nonsynonymous mutations. The outcome of the protein-ligand interaction with the active compound of ARs shows a promising lead to the development of resistance towards Brodifacoum, Flocoumafen, and Bromadiolone. This result is important to determine which type of ARs are safe to use in the oil palm plantation to control the rats. Analysis between resistant (R-) and susceptible (S-) populations of R. tiomanicus resulted in a negative result of Tajima’s D and significant FST, implying a recent population expansion that was caused by balancing selection due to rodenticide use in the oil palm plantation. The population is at a high risk if a large number of resistant individuals migrate from outside the treated region, the frequency of resistance may develop more rapidly than expected by rodenticide usage. Thus, control programs should be coordinated between neighbouring plantations within each population for successful and more effective eradication campaigns, as well as to limit the frequency of rodenticide resistance in oil palm plantations.

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