Marmoset study establishes standards for the new era of biodiversity genomics

The international consortium today announces a series of publications in a special collection of Nature that resulted from the first phase of the Vertebrate Genome Project (VGP) to release 16 high quality reference genomes. The research group led by Professor Guojie Zhang of the Department of Biology has made substantial contributions to the VGP and this first wave of publications.

In collaboration with VGP, the research group has published a research paper in Nature on platypus and echidna genomes early this year (see report in the right column). In the Nature current special issue, the research group published another study on the genome of the common marmoset, an important primate model for neurodegenerative diseases, drug development and other biomedical research.

The genome includes two sets of chromosomes, one inherited from the mother, the other from the father. In traditional genome sequencing efforts including the human genome project, the sequencing only produced a mosaic reference genome mixing randomly with sequences from the maternal or paternal chromosomes. Now, the research group reported a new strategy to produce completed assemblies of the two sets of genomes independently into chromosomal level. They have applied this method to produce the diploid genomes of a male common marmoset and showed huge number of variations between the two paternal genomes that previous genomic sequencing methods could not obtain. The study has established standards for the new era of biodiversity genomics.

The two parental genomes in our cell are not completely identical but have different nucleotide compositions. These differences can affect the function of genes and also our health. Some of these differences in men, for examples, the X chromosome from our mother and Y chromosome from our father have different structures and harbor genes with intensified sexual conflicts."

Guojie Zhang, Study's Senior Author

The researchers have sequenced a trio (the mother, father and a male offspring) of the common marmosets. Taking advance of the long reads sequencing technology, now the researchers can distinguish the two parental genomic sequences in the male offspring based on the genomic features from the mother and father. For the first time, the researchers present a completed diploid genome with two sets of paternal chromosomes have been assembled independently into chromosome level.

- "This allows us to detect large genomic variations between the parental genomes, " says Chentao Yang, who is a BIO-BGI joined PhD student and the first author of this paper, 'surprisingly, we found the heterozygosity level in the diploid genome is 10 times higher than that can be revealed by previous method'.

The completed assembly also allows the researchers to closely investigate the structure and evolution of the sex chromosomes in this primate species. This New World Monkey species has different structure of sex chromosome than our human. A lineage-specific inversion occurred on the Y chromosome of the common marmoset leading to a more degenerated Y chromosome in this species.

The study also discovered genetic changes occurred in common marmosets that might explain many unique biological traits in this species, such as small body size, high frequency of twin born, gum chewing, and maintaining bone density during aging. Some genes related to the gonadotropin releasing hormone and fertility have accumulated mutations that might provide selection advantage for these animals to produce more twin offspring. The changes on the gonadal estrogen and genes involved in osteoclastogensis and bone metabolism might explain why this primate species does not suffer from osteoporosis during aging because of the reduced level of gonadal estrogen which other primates including human would experience.