Identity-by-descent analyses for measuring population dynamics and selection in recombining pathogens

Area of Science:

• Genomics
• Population Genetics
• Parasitology

Background:

• Identical by descent (IBD) analysis is crucial in human genetics but underutilized in pathogens.
• Existing methods lack statistical approaches for non-diploid genomes and multiclonal infections.

Purpose of the Study:

• To develop a novel methodology for IBD analysis in haploid microorganisms with multiclonal infections.
• To create a statistic for identifying positive selection and explore relatedness networks.
• To apply these methods to Plasmodium falciparum whole genome sequencing data.

Main Methods:

• Developed isoRelate, a new IBD detection methodology for haploid organisms.
• Introduced a novel statistic for detecting positive selection.
• Constructed relatedness networks to visualize haplotype sharing.
• Analyzed over 2500 Plasmodium falciparum genomes.

Main Results:

• Identified Southeast Asia as a hotspot for highly related Plasmodium falciparum isolates.
• Detected numerous selection signals, many linked to known drug resistance genes.
• Discovered two novel selection signals in multiple countries.
• Observed intercontinental spread of one drug resistance sweep and independent emergence of another.

Conclusions:

• isoRelate is a valuable tool for exploring microbial population structure, selection, and haplotype distributions.
• The findings provide insights into Plasmodium falciparum evolution, drug resistance, and population dynamics.
• This methodology can aid in monitoring and controlling infectious diseases.