First complete marmoset genome
To study complex diseases like Alzheimer’s, scientists and clinicians analyze how genes change and malfunction in other species. Marmosets, a species of tiny monkey from South America, have become an important animal to study for understanding disease—but researchers have never had a complete baseline for understanding the primate’s DNA.
Now, the first complete genome of the common marmoset is available to the scientific community. With this resource, researchers will be able to study marmoset genetics with high accuracy and detail, revealing unseen features and enabling future insights into disease and evolution. The results are detailed in a study published today in Cell.
Marmosets are increasingly studied by scientists because as a new world primate, they are more closely related to humans than other model species like mice, while their small size makes them easier to work with than other primates like macaques. New-world primates like marmosets experience age-related memory loss, which has made them a great model for studying these conditions.
To study the genetic makeup of a species, scientists use a standardized DNA sequence called a reference genome. By comparing individuals to this reference, they can make insights into disease, traits, and evolution.
Scientists created the first marmoset reference genome in 2014, but this version contained gaps and errors, and left several regions of the genome unresolved, making it difficult for researchers to accurately identify genetic variation.
The updated reference resolves these errors and provides the first record of several complex features of the marmoset genome. The researchers used the new reference to examine genetic differences across 230 marmosets, finding variation at many of the genes linked to Alzheimer's disease in humans, and those vital to the immune system.
Because the marmoset is increasingly relevant as a model for studying neurodegenerative diseases, the researchers specifically searched for a shortlist of genes known to be linked to Alzheimer’s, Parkinson’s, and related neurodegenerative diseases in humans and provided high-quality references for 76 instances of matching genes in marmosets. This will enable other scientists to study the health impacts of these genes with much higher accuracy.
“We see variation in these marmosets in the same genes that we do in humans, further reinforcing the idea that the marmoset is a good model for studying Alzheimer’s disease in humans,” the first author said. “Now, we have this really complete, high-quality resource that people can take advantage of.”
Using their new reference along with transcriptomic data, which allows researchers to see which genes are “turned on” and “turned off,” the team identified previously undescribed forms of several genes, including the PSEN1 gene, which is the most frequent cause of early-onset familial Alzheimer's disease
The Major Histocompatibility Complex (MHC) is a cluster of genes that underlies the immune system, and is known to influence many autoimmune and other diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. The researchers provided a complete record of the marmoset MHC region, annotating several complex, previously un-catalogued genes.
The complete genome also revealed that marmosets shuffle sets of ribosomal DNA (rDNA), a crucial subset of DNA that enables protein production, between chromosomes more freely than expected, gaining and losing whole arrays on individual chromosomes in ways not previously documented in primates.
“We also identified sex differences in the distribution of these genes, a pattern that has previously been reported in orangutans and gibbons, widening our understanding of these genes that are extremely important to the biosynthesis of cells,” the senior author said. “While these sex differences may not have an effect on the species, now that we can do T2T sequences, we’ll find out more.”
The researchers also identified patterns in the centromeres, regions of the chromosomes vital for cell division, that will warrant further study.
