A Baylor College of Medicine and Washington University in St. Louis-led worldwide team of researchers has completed the genome sequence of the common marmoset, which is the first sequence of a New World Monkey. Recently published in the journal Nature Genetics, the study provides new information on the marmoset’s unique rapid reproductive system, physiology, and growth, and sheds new light on primate biology and evolution.
“We study primate genomes to get a better understanding of the biology of the species that are most closely related to humans,” said Dr. Jeffrey Rogers, associate professor in the Human Genome Sequencing Center at Baylor and lead author of the report. “The previous sequences of the great apes and macaques, which are very closely related to humans on the primate evolutionary tree, have provided remarkable new information about the evolutionary origins of the human genome and the processes involved.”
The sequence of the marmoset enabled the team to reveal first-hand the genome of a non-human primate in the New World monkeys, which forms a separate branch in the primate evolutionary tree more distant from humans than those whose genomes had previously been studied in detail. Researchers’ ability to study the human genome and its history as revealed by comparison with other primates has now been broadened.
Led by Dr. Kim Worley, professor in the Human Genome Sequencing Center, and Rogers at Baylor, and Drs. Richard K. Wilson, director, and Wesley Warren of The Genome Institute at Washington University, in collaboration with Dr. Suzette Tardiff of The University of Texas Health Science Center in San Antonio and the Southwest National Primate Research Center, the sequencing was conducted as a joint project by Baylor and Washington University.
“Each new non-human primate genome adds to a deeper understanding of human biology,” said Dr. Richard Gibbs, director of the Human Genome Sequencing Center at Baylor and a leading investigator of the study.
The research revealed unique genetic features observed in the marmoset, including a number of genes that are thought to be responsible for the marmoset’s ability to consistently produce multiple births.
“Unlike humans, marmosets consistently give birth to twins without the association of any medical issues,” said Worley. “So why is it OK in marmosets but not in humans where it is considered high risk and associated with more complications?”
The marmoset gene WFIKKN1 presents changes associated with twinning in those animals.
“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 Rogers, adding that this finding could apply to studies of multiple pregnancies in humans.
The team has also looked for genetic changes associated with a unique trait found in marmosets and close relatives, which had not been described in any other mammals. The dizygotic (or fraternal) twins in marmosets exchange stem cells called hematopoietic stem cells in utero, leading to chimerism, a single organism composed of genetically distinct cells.
“This is very unusual. The twins are full siblings, but if you draw a blood sample from one animal, between 10 and 50 percent of the cells will carry the sibling’s DNA,” Rogers explained. “Normally, fraternal twins do not share the same DNA in this way, and in other animals, this chimerism can cause medical problems but not in marmosets. It is very unique.”
“The translational implications of this work to pregnancy and reproductive medicine are significant. We have shown that there are several genes in the marmoset which likely enable twinning. However, it is not just a question of why they have such a high rate of twinning, but how do they manage to rear and raise these twins so successfully,” said Dr. Kjersti Aagaard, associate professor of obstetrics and gynecology — maternal fetal medicine at Baylor and co-author on the study. “Given the relatively high rate of complications of twins we see, ranging from preterm birth to unique complications such as Twin Twin Transfusion Syndrome (seen only amongst identical or monochorionic twins), it is crucial to understand the underlying adaptive biology of the marmoset which enables them to avoid these complications.”
In marmosets’ unique social system, the dominant male and female are the primary breeders for a family, but their relatives also care for the offspring, providing all the support and allowing the breeders to reproduce again quickly. It is interesting to observe that the relatives who provide such care are reproductively suppressed, as Worley explained.
“This species is clearly adapted to rapid reproduction and to the potential for rapid population expansion,” said Rogers. “Their ecological system connects with that as they are able to thrive in disturbed areas of forests. So one possibility is that they have evolved a feeding and dietary regimen that allows them to live in these type of conditions where they can reproduce quickly. This would be advantageous as any adults that move into a newly disturbed area would establish their offspring as the early initial residents of the newly available area.”
Another characteristic of the marmosets is their very small body size. According to the genome sequence, this may result from positive selection in five growth hormone/insulin-like growth factor axis genes (GH-IGF) with potential roles in producing small body size.
The team has also identified a cluster of genes affecting metabolic rates and body temperatures, adaptations usually associated with the challenges posed by small body size.
Additionally, the study provides new information about microRNAs, small non-coding RNA molecules that function to regulate gene expression.
“There has not been much research conducted on microRNAs in nonhuman primates, so we found this particularly important,” said Worley.
A team led by Dr. Preethi Gunaratne, an associate professor of biology and biochemistry at the University of Houston and of pathology and a member of the Human Genome Sequencing Center at Baylor, and Dr. R. Alan Harris, an assistant professor of molecular and human genetics at Baylor, has found that marmosets exhibit a significant number of differences in microRNAs as well as their gene targets as compared to humans, with two large clusters that could be involved in reproduction.
This newly completed sequence paves the way for further biomedical research using marmosets, said Rogers. “Researchers may have been more reluctant to study the marmoset due to lack of basic information, but this genome sequence opens new avenues for future research relevant to various aspects of human health and disease.”
Dr. Suzette Tardiff, professor of cellular and structural biology at the Barshop Institute for Longevity and Aging Studies at The University of Texas Health Science Center at San Antonio, a core scientist at the Southwest National Primate Research Center is an expert in marmoset biology and co-authored the paper. She provided fundamental information on the biology of marmosets, and helped researchers obtain samples for the sequence.