Challenges in estimating effective population sizes from metagenome-assembled genomes

Area of Science:

• Microbial Ecology
• Evolutionary Biology
• Genomics

Background:

• Effective population size (N) is crucial for understanding microbial ecological dynamics and the balance between selection and drift.
• Estimating N typically requires neutral genetic diversity from closely related genomes, but culturing difficulties limit this for many prokaryotes.
• Metagenome-assembled genomes (MAGs) offer a high-throughput alternative for genomic data, but their accuracy for N estimation is unverified.

Purpose of the Study:

• To evaluate the reliability of MAGs for estimating effective population size (N) in microbial populations.
• To compare N estimates derived from MAGs versus traditional isolate-based methods.
• To identify factors contributing to discrepancies in N estimates between MAGs and isolates.

Main Methods:

• Examined the Thermococcus genus using 66 isolated strains and 29 MAGs.
• Compared phylogenetic distribution and average nucleotide identity (ANI) between isolate and MAG populations.
• Analyzed N estimates derived from both isolate and MAG data across multiple bacterial genera.

Main Results:

• MAG populations consistently yielded lower N estimates compared to isolate populations within the Thermococcus genus.
• This N underestimation trend was also observed in MAG populations of three other bacterial genera.
• Underestimation is likely due to the underrepresentation of genetic variation, including allele frequency data and variable genomic segments, in MAGs.

Conclusions:

• MAGs may underestimate effective population size (N) due to inherent limitations in capturing genetic diversity.
• Caution is advised when utilizing MAGs for evolutionary studies that rely on accurate nucleotide-level diversity and genome assemblies.
• Further validation and methodological improvements are needed for robust evolutionary inference from MAGs.