Direct long-read visualization reveals hidden variation in GCH1 gene copy number and precise expansion steps.

ABSTRACT:

Background

Increases in the copy number of large genomic regions, termed amplifications, are an important adaptive strategy for many organisms. Numerous amplifications across the AT-rich Plasmodium falciparum genome contribute directly to drug resistance or impact the fitness of this protozoan parasite. During the characterization of malaria parasites selected with a dihydroorotate dehydrogenase (DHODH) inhibitor that targets pyrimidine biosynthesis, we detected increased copies of a genomic region that encompassed 3 genes (~ 5 kb) including GTP cyclohydrolase I (GCH1 amplicon). While amplification of this gene is reported in antifolate-resistant parasites, GCH1 amplicons had not previously been implicated in DHODH inhibitor resistance.

Results

Here, we explored the expansio

SUBMITTER: Liu S 

PROVIDER: S-EPMC12273453 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature