Structural polymorphism and diversity of human segmental duplications.

Area of Science:

• Genomics
• Population Genetics
• Human Evolution

Background:

• Segmental duplications (SDs) are crucial for human evolution, diversity, and disease.
• Resolving SDs at the sequence level has been a significant challenge in genomics.

Purpose of the Study:

• To conduct a population genetics survey of segmental duplications (SDs) using long-read genome assemblies.
• To identify and characterize fixed versus structurally polymorphic SDs.
• To investigate population-specific differences in SDs and their impact on gene families.

Main Methods:

• Analysis of 170 human genome assemblies with long-read sequence data.
• Identification and quantification of duplicated sequences, distinguishing fixed and polymorphic events.
• Comparison with Iso-Seq read data to identify novel genes within SDs.

Main Results:

• Fully resolved the majority of SDs across 170 human genome assemblies.
• Identified 173.2 Mbp of duplicated sequence, including 47.4 Mbp not in the reference genome.
• Found intrachromosomal SDs to be highly variable, with African genomes showing significantly more SDs and higher gene copy numbers for duplicated families.
• Discovered 201 novel, potentially protein-coding genes associated with copy number polymorphic SDs.

Conclusions:

• Long-read sequencing enables comprehensive resolution of segmental duplications.
• Significant population differences exist in SDs, particularly between African and non-African genomes.
• SDs contribute to novel gene discovery and human genetic variation.