Scientists would rely on Whole Genome Sequencing (WGS) to compare the Shelekhov isolate against local wildlife strains, specifically those from marmots and ground squirrels. A natural spillover typically mirrors the genetic diversity found in these regional reservoirs. If the outbreak strain is nearly identical to a known laboratory reference strain or a distant lineage not present in Siberian fauna, the evidence points toward a leak.
Single Nucleotide Polymorphism (SNP) analysis allows for the construction of high-resolution phylogenetic trees. This reveals the evolutionary trajectory of the pathogen. A natural event shows a slow genetic drift. In contrast, a lab leak often looks like a sudden appearance of a dormant or foreign strain, lacking the expected intermediate mutations from local wildlife.
Investigators would also examine the pPCP1 and pMT1 plasmids for anomalies. Unusual insertions or synthetic markers would be definitive. By calculating the molecular clock, researchers can determine when the strain diverged from its ancestor. If this date clashes with the known biology of local rodent cycles, a laboratory origin becomes the most plausible explanation.