Contributed by Rafael Palacios, February 17, 2021 (sent for review December 7, 2020; reviewed by Jef D. Boeke, Patricia L. Foster, and Joseph Schacherer)The accuracy of the nucleotide sequence of genomes is of utmost importance. The Perfect Match Genomic Landscape (PMGL) is a precise, sensitive, and nonstatistical strategy to detect genome variation. We used this strategy to refine reference genomes from microorganisms belonging to the three domains of life. Our studies show as well that the PMGL can be useful to detect variants in pathogen agents during a pandemic, and to isolate mutations...…Contributed by Rafael Palacios, February 17, 2021 (sent for review December 7, 2020; reviewed by Jef D. Boeke, Patricia L. Foster, and Joseph Schacherer)The accuracy of the nucleotide sequence of genomes is of utmost importance. The Perfect Match Genomic Landscape (PMGL) is a precise, sensitive, and nonstatistical strategy to detect genome variation. We used this strategy to refine reference genomes from microorganisms belonging to the three domains of life. Our studies show as well that the PMGL can be useful to detect variants in pathogen agents during a pandemic, and to isolate mutations...WW…