Black Ice, Lake Baikal, Russia by Sergey Pesterev
Fossils are the remains of living organisms which are preserved by very specific conditions and covered by layers of sediment, mud, or tar. As it turns out, ice can encapsulate and protect the remains of animals too though not to the same degree. Typically when cells freeze they undergo lysis which causes their cell membranes to rupture and their contents to spill out or mix with environmental substances. While this kills the organism, it may not entirely destroy the living organisms machinery. A mammoth found in the Siberian permafrost seems protected from the environment and was carbon dated to be around 28,000 years old. As it turns out, this unconventional preservation may still hold some interesting details.
Yamagata et. Al. not only analyze the cells from the nicknamed woolly mammoth “Yuka,” but also test the capabilities of our current technology. They take special care in identifying the integrity of their subject samples, and rightly so given that Yuka was found in atypical preservation conditions. They begin by analyzing the proteins present in their samples and comparing them with similar species of elephants and elephantids. By studying the proteome, the collection of all generated proteins of an organism, they identify common proteins between that of Yuka and other elephant species such as Loxidonta africana, Elephas maximus, and Mammut americanum. These matched species helped identify changes in the proteome that may be specific to Yuka of the Mammothus primigenius species. They find 869 distinct proteins, of which 192 are found in bone marrow, 461 from muscle tissues, and 216 which are found in both. This shows that these tissues were preserved adequately and that there are a lot of conserved proteins specific to the tissues. They also observed specific changes to eight protein such as Laminin subunit gamma and find that among those, only 13 non-synonmymous substitutions occured in the amino acids that made up the proteins. This is most likely only a fraction of all the changes that occurred but it still gives a good idea of the amount of preservation the mammoth received.
In addition to this, the team wanted to test the amount of deterioration the proteins may have undergone. They do this by a method developed by van Doorn, referenced in their paper, which entails quantifying the amount of deamidations in the proteins. Deamidations are changes in specific amino acids such as glutamine or asparagine whereby they can interact with other nearby amino acids. Asparagine for example can undergo a condensation reaction to form aspartic acid. By finding the amino acids in the protein chains that were deaminated, they can compare the amount of deterioration that the proteins have experienced. Yamagata and colleagues find that of the bone marrow and muscle samples, the bone marrow experience more deterioration showing more deamidation. As such it seemed that muscles were more conserved which suggested their data would provide more acccurate pre-mortem information.
Observing the samples, they also found histones, histone chaperones, and other proteins as well as methylation of the histones. This suggested that the cells may still be able to function properly given the right conditions. As such they may be reconstituted using other cells via a process known as nuclear transfer. Nuclear transfer is typically the process by which DNA is removed from a cell and replaced with another in hopes of making a pluripotent cell with the new DNA. In this case however, the study attempts to find if the proteins from the mammoth cell are able to promote the growth and division of the cell. While they struggle to find mammoth DNA intact, they are able to conclude that the proteins are suitable not only for some mitotic processes, but also for reforming nuclear blebs. These blebs were taken as initial or not complete forms of a cellular nucleus. As such the team is hopeful that with the right sample or another preserved specimen, the mammoth cell could be reconstituted using a mouse oocyte similar to this.
In the paper, the team mentions that not only had nuclear transfer processes in the past failed readily, but they had rarely been successful in showing hopeful signs of nucleas-like structures form. In light of this it seems that their findings are encouraging as it may be possible to generate a reconstituted mammoth cell. As they mention however, it would take a sample with intact DNA in order to do so. Despite this, the team was able to show that it is not entirely impossible and tested the full capabilities of nuclear transfer. This is equally as important given that without testing, we would not know what the technology is able to do. As of now they state that some fine tuning is necessary to perform a seamless transfer as well as using the right samples in order to create a mammoth cell.
In Depth
Overall the study does a fine job of taking purposeful steps in identifying their sample subject. They are able to clarify that the proteins are what they think they are and that there was no contamination from the environment or additions from other areas. A lot of work was put into collecting different data to test their hypothesis. As such it would be helpful to spend more time on the figures and the corresponding legends to explain them. A lot of the paper could be condensed to make statements clearer while a lot of data analysis and explanations could be fleshed out further. As the paper stands it requires a lot more focused reading and understanding of the jargon and techniques used in the paper. Of course this could be said of many papers and it is understood that a good paper must be concise, however this particular paper might need more of this work than most. There are also a lot of references to supplemental figures which, for the same issue of conciseness, have not been directly included but perhaps should have been considering the amount of support it might gain from them. The evidence presented do suggest that the samples are relatively uncontaminated and depict the mammoth individual. In addition they make good points as to the use of the conclusions made and the reflection of the function and efficacy of current nuclear transfer techniques among others. Much of their methods were written out concisely and remained accurate enough to reproduce the results.
Yamagata, K., Nagai, K., Miyamoto, H., Anzai, M., Kato, H., Miyamoto, K., … & Plotnikov, V. V. (2019). Signs of biological activities of 28,000-year-old mammoth nuclei in mouse oocytes visualized by live-cell imaging. Scientific reports, 9(1), 4050.
Sergey Pesterev. https://unsplash.com/@sickle
Unsplash. https://unsplash.com
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