To better understand what drives biodiversity on Earth, scientists have historically looked at genetic differences between species. But this only provides part of the picture. The traits of a particular species are not only the result of its genes but also the proteins that those genes code for. 4
Therefore, understanding the differences between species proteins—or all the proteins that can be expressed—is just as important as understanding the differences between genomes.
In a new study, Yale University researchers compared the proteins of skin cells from 11 mammals, which, they say, will help scientists understand the molecular drivers of biodiversity and how these factors have evolved over time.
They found that while many proteins are similarly variable across and within species, some are more diverse between species, providing clues about which proteins may be more important in mammalian evolution. The work may also help researchers understand why some types are so resistant to cancer.
Their findings were published on September 9 science progress.
“In order to understand biodiversity, along with knowing how DNA differs across species, you may also want to know how species behave, evolve, and look differently,” Gunther WagnerAlison Richard Emeritus Professor of Ecology and Evolutionary Biology.
And these traits — how the species looks, behaves, and develops — are thought to have more to do with protein levels than with DNA. Liu Yanshengassistant professor of pharmacology at Yale University School of Medicine.
Comparing protein amounts across species has been challenging, as there is no technology to perform large-scale analyzes. But Liu applied a method called mass spectrometry to the data-independent acquisition that now allows researchers to do this kind of work.
““It’s a conceptual and technical breakthrough that allows us to work at this higher, more functionally relevant level,” Wagner said.
Liu is a member of the Institute for Cancer Biology at Yale University, and Wagner is a member of the Institute for Systems Biology, both located on Yale University’s Western Campus. It was there, during a Cancer Systems Biology symposium that they both attended, that their collaboration began.
For the study, the researchers quantified all proteins expressed in the skin cells of 11 mammal species: rabbits, rats, monkeys, humans, sheep, cattle, pigs, dogs, cats, horses, and opossums.
They found that the analysis provided information that could not be obtained through other techniques. For example, while previous research investigated differences in mRNA – the genetic material used to make proteins – they found that measuring proteins provides additional information that cannot be captured by mRNA analysis alone, since mRNA is only an indirect measure of protein abundance.
A strand of mRNA carries the protein composition code. Liu explained that while single proteins can have a specific function, proteins can also interact with each other and act as groups. Just looking at mRNA will not provide this information.
“We found that the relationship of protein to mRNA is very low, especially for certain classes of proteins.” “This means that the mRNA profile alone would be misleading.”
The team then looked at protein variability across species and across individuals within the same species, and found that for most proteins, levels that were most variable between individuals were also more variable between species. But there were some proteins that did not fit this trend. For example, proteins related to cell division and RNA metabolism were more variable between species than among individuals of a single species (humans, in this case). This suggests that these functions play a particularly important role in mammalian evolution, the researchers said.
““The differences between species versus differences between individuals are very interesting from an evolutionary point of view,” Wagner said. “Comparing the two gives us an idea of how much variance is allowed within species and we can use this information to predict the ability to evolve.”
Finally, the researchers compared the protein removal systems across species. There are two main systems responsible for removing proteins in cells, and they found that one was similar across species while the other showed a great deal of variation between different mammals.
Wagner added that this protein turnover rate determines how quickly a cell can change its state. “If a new signal appears, the cell needs to get rid of the proteins that were necessary for its previous state and create new ones,” he said.
And how quickly a cell’s condition changes can be related to cancer.
““Healthy cells can be affected by nearby cancerous cells,” Wagner said. It will be important to understand whether protein turnover rates are related to how well cells react to the effects of cancer cells. Species that are more resistant to cancer, such as hoofed animals such as cows and pigs, probably have cells that are less able to alter their state and are less susceptible to signals than cancer cells. “
Understanding cancer susceptibility is just one potential application of this work, the researchers said. For example, they can begin to relate protein differences to any other traits that differ across species, says Liu.
Proteins undergo chemical modifications that occur when other molecules attach to a protein and activate or deactivate it. These modifications contribute to traits that differ between and within species because they play a major role in influencing protein function. The researchers evaluated one type of modification in this study, phosphorylation, and found that differences in phosphorylation levels were, for the most part, unrelated to differences in protein abundance, providing another layer of understanding about what drives biodiversity. The researchers will continue to evaluate other modifications in future work.
“It would provide a more complete picture,” Liu said, adding that it is the biological differences between species and individuals that shape biodiversity on Earth. “Measuring differences in both proteins and modified proteins across species will advance our understanding of biodiversity at the molecular level.”
Reference: Ba Q, Hei Y, Dighe A et al. Proteotypic coevolution and quantitative diversity across 11 mammal species. Science fiction attorney. 8 (36): eabn0756. dui: 10.1126 / sciadv.abn0756.
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