Probability-Based Sequence Comparison Finds Pre-Eutherian Nuclear Mitochondrial DNA Segments in Mammalian Genomes

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Nuclear-mitochondrial DNA segments (NUMTs) arise from mitochondrial DNA insertions into the nuclear genome.
• NUMTs are significant drivers of genome evolution and can acquire new cellular functions.
• Existing methods struggle to detect ancient and degraded NUMTs, underestimating their prevalence and impact.

Purpose of the Study:

• To identify ancient NUMTs in mammalian genomes using advanced high-sensitivity sequence comparison.
• To provide a comprehensive analysis of the quantity and evolutionary history of mammalian NUMTs.

Main Methods:

• Development of a sensitive and accurate NUMT searching pipeline.
• Application of enhanced high-sensitivity sequence comparison methods for NUMT detection.

Main Results:

• Prediction of 1013 NUMTs in the human reference genome, with 364 (36%) being newly identified.
• Discovery of 90 pre-eutherian human NUMTs, dating back at least 100 million years.
• Identification of the most ancient mammalian NUMT originating over 160 million years ago in the common ancestor of therian mammals.

Conclusions:

• Ancient NUMTs play a substantial role in genetic functions, potentially contributing to functional exon acquisition.
• This research offers a deeper understanding of NUMT abundance and evolutionary trajectories in mammals.
• The findings pave the way for future studies on endosymbiotic influences on nuclear genome evolution.