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We present the first telomere-to-telomere (T2T) reference genome for the common marmoset, a vital model organism. This high-quality genome resolves complex regions, enhancing its use in studying primate evolution and human diseases.

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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.