We use the grey short-tailed opossum, Monodelphis domestica, as a model system to answer questions relating to our own evolutionary transition from “reptile” to mammal and the process of aging in mammals.
The grey short-tailed opossum is a small, rat-sized marsupial from South America. Opossums are nocturnal, solitary, breed year round, and, unlike their North American cousins, do not have a pouch.
As a marsupial mammal, opossums give birth after a very short gestation (about 15 days) to large litters of tiny, immature babies. These babies complete their development while attached at the mother’s nipple. Opossums are born at a developmental stage similar to a human baby at 40 days post-fertilization developing in its mother’s womb.
Opossums are also born with many “reptile”-like traits, discussed in detail below. The physical changes that occur during an opossum’s development mirror those that occurred during the transition from “reptile” to mammal during our own evolutionary history.
Opossums have other unique adaptations with relevance to human health. For example, opossum spinal cords can completely regenerate for several days after birth. Opossums can also develop melanomas through exposure to UV light, similar to humans.
IUCN Red List of Threatened Species, species assessors and the authors of the spatial data. / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)
The mammalian middle ear is a textbook example of evolutionary transformation and one of the few, key bony hallmarks for the origins of mammals in the fossil record. “Reptiles” possess many bones in the jaw but only a single bone (stapes) in the middle ear. In contrast, all mammals possess a single bone in the jaw, and many bones in the middle ear in addition to the stapes. On this page “reptiles” is in quotes because in scientific-speak the term reptiles includes reptiles and all of their descendants, meaning that birds and sometimes even mammals are reptiles! We use “reptiles” to refer to the ancestors of modern mammals and birds, and sauropsids. These extra bones migrated from the “reptile” jaw to the mammal middle ear over the course of evolution. Amazingly, opossums are born with these extra bones still attached to the jaw, like in adult “reptiles”. As they grow up, the bones migrate to the middle ear. We can therefore study opossum development to gain insights into how mammals, and their middle ears, evolved.
Opossum aging differs in several ways from that observed in all other mammals. We are taking advantage of this fact and using opossums as an “exception that proves the rule” to study the role of developmental processes and other biological drivers in aging in mammals, including humans.
Mammalian development and aging are linked
The universality of aging across mammals has engendered much speculation on its causes. In collaboration, we developed “aging clocks” that use methylation patterns to can estimate age across mammal tissues and species. Digging deeper, clock results also suggest that development and aging are linked in most mammals because of their shared reliance on the same methylation machinery. The only mammal lacking this link appears to be opossum, the “exception that proves the rule.”
Mammal middle ear bones came from the “reptile” jaw
The possession of a middle ear with several bones is a key mammalian trait. We linked small changes in genes and cells to the separation of the future middle ear bones from the jaw during opossum development. This suggests that it might have been relatively easy for mammals to re-purpose parts of their jaw to make a middle ear. This finding, and others, support the hypothesis that more than one group of mammals independently evolved a middle ear made up of several bones.
Opossums respond to thalidomide like humans
The drug thalidomide has caused disabilities in thousands of children. However, how thalidomide disrupts development in humans remains unresolved. This is, in part, because thalidomide does not disrupt rodent development. We found that opossum embryos exposed to thalidomide display malformations similar to humans. Our findings suggest that opossums make a good mammalian model for future studies of the impact of thalidomide, and other teratogens, on human development.
Our research in opossums has potential to:
Reveal how teratogens disrupt normal development in mammals, including humans
Unravel the relationship between development and aging in mammals, including humans
Decode the developmental rules that have shaped the evolution of form in mammals, including humans
Illuminate the evolutionary transition from “reptile” to mammal
