A Complete Genome for the Common Marmoset

Area of Science:

• Genomics
• Primate Evolution
• Comparative Genomics

Background:

• The common marmoset is a widely used New World monkey (NWM) model organism for studying primate evolution and human diseases like Alzheimer's and neuropsychiatric disorders.
• Existing genomic resources for marmosets have limitations in resolving complex and rapidly evolving genomic regions.

Purpose of the Study:

• To generate the first telomere-to-telomere (T2T) high-quality reference genome assembly for the common marmoset.
• To enable deeper insights into complex genomic structures, including centromeres, sex chromosomes, ribosomal DNA (rDNA), and the major histocompatibility complex (MHC).
• To improve the common marmoset's utility as a biomedical model organism and advance understanding of primate evolution.

Main Methods:

• Utilized long-read sequencing technologies to achieve telomere-to-telomere (T2T) genome assembly.
• Generated an additional near-T2T assembly from a second individual to obtain four high-quality haplotypes.
• Employed comparative genomic analyses to investigate centromere structure, rDNA organization, MHC genes, and pseudo-homologous regions (PHRs).

Main Results:

• Delivered the first T2T reference genome for the common marmoset, adding over 88 Mb of sequence and resolving previously challenging genomic regions.
• Fully resolved all marmoset centromeres, revealing chromosomal-specific dimeric alpha satellites and evidence of ancestral centromere turnover.
• Identified novel marmoset-specific MHC genes and over 500 transcribed genes unique to the marmoset lineage, alongside a sexually dimorphic rDNA structure.
• Constructed a marmoset pangenome using multiple long-read assemblies, providing a robust reference for short-read mapping.

Conclusions:

• The T2T marmoset genome provides an unprecedentedly accurate and complete reference, significantly enhancing its value as a biomedical model.
• Resolved genomic features like centromeres, rDNA, and MHC offer new avenues for research into primate evolution and disease mechanisms.
• The developed pangenome resource will improve genetic studies across diverse marmoset populations and facilitate comparative genomics.