Parent-progeny sequencing indicates higher mutation rates in heterozygotes

Area of Science:

• Genetics
• Evolutionary Biology
• Genomics

Background:

• Mutation rate variation within genomes is observed but poorly understood.
• Previous studies often relied on indirect methods, potentially introducing bias due to selection.
• Directly observing mutation events is crucial for accurate rate determination.

Purpose of the Study:

• To directly quantify mutation rates across different genomic contexts.
• To investigate the influence of heterozygosity and recombination on mutation rates.
• To reconcile observed patterns of mutation rate variation with genomic diversity.

Main Methods:

• Employed a parent-offspring sequencing strategy for direct mutation calling.
• Utilized Arabidopsis for primary study, with rice and honey bee as replication models.
• Analyzed mutation proximity to heterozygous sites and crossover events.

Main Results:

• Mutation rates are significantly higher in heterozygous regions compared to homozygous regions (approx. 3.5-fold).
• Increased mutation rates are observed in proximity to meiotic crossover events.
• A correlation exists between recombination rate and intraspecific diversity, partly due to higher mutation rates in high-recombination domains.
• Pathogen resistance genes, often under balancing selection, exhibit a ten-fold higher mutation rate.

Conclusions:

• Genomic heterozygosity and recombination directly influence mutation rates.
• Observed mutation rate patterns can be explained by direct effects rather than solely selection on mutation rate.
• This provides a mechanistic explanation for mutational hot and cold spots corresponding to different selection regimes.