White-Tufted-Ear Marmoset (Callithrix jacchus).

Marmoset Genome Sheds Light on Primate Biology and Evolution

A team of international researchers, led by The Genome Institute at Washington University in St. Louis and Baylor College of Medicine, have reported the whole-genome sequence of the common marmoset (Callithrix jacchus) in Nature Genetics.

The common marmoset, native to east-central Brazil, is a New World Monkey that routinely produces healthy dizygotic (fraternal) twins that exchange hematopoietic stem cells in utero. This twinning and exchange results in blood containing a substantial proportion of leukocytes acquired from its co-twin (chimerism). Additionally, marmosets are unusual in their small body size when compared to other primates.

Sequencing and Analysis

The whole genome of a female marmoset (2.2-gigabases, representing 90% of genome) was assembled using Sanger read data (6x) and a whole-genome shotgun strategy. Blood DNA contained sequences from the germ line and also from her co-twin. Since the co-twin was male, researchers were able to estimate the proportion of reads originating from the co-twin, which indicated 10% were derived from the co-twin. Analysis showed that the marmoset gene WFIKKN1 exhibits changes associated with twinning. A single, nonsynonymous substitution in this gene was common to all callitrichids except one species, which does not regularly twin.

“From our analysis it appears that the gene may act as some kind of critical switch between multiples and singleton pregnancies, though it is not the only gene involved,” said Dr. Jeffrey Rogers of Baylor, who added the finding could apply to studies of multiple pregnancies in human.

The genome sequence showed the small size of marmosets may be the result of positive selection in five growth hormone/insulin-like growth factor axis genes (GH-IGF) with potential roles in producing small body size. Additionally, the team identified a cluster of genes that affect metabolic rates and body temperatures, adaptations associated with challenges of small body size

Comparative Analysis of miRNA

777 mature miRNAs (mapped to 1,165 hairpin precursor miRNAs) were identified and most confirmed through expression. Many (377) mature miRNAs were novel, not found in any other species analyzed. Comparing the annotated genes containing predicted let-7 target sequences, researchers found 165 common to human marmoset, 44 unique to marmoset, and 64 unique to humans.

Model for Human Diseases

"The marmoset is an excellent model for the study of many of the same diseases that afflict humans, including Parkinson’s disease and multiple sclerosis, among others," said TGI's Dr. Richard K. Wilson. "Our marmoset genome reference has already provided insight into key comparative differences with the other widely used non-human primate model, rhesus macaque. We hope this first examination of the marmoset genome will facilitate discoveries that accelerate therapeutic intervention strategies in humans," Wilson added.