Integrated bug management

In late 1970s, agriculture encountered a major crisis in pesticide resistance leading to the near-collapse of the cotton industry in several countries. This crisis forced the industry to devise the Integrated Pest Management (IPM), an approach that aims to minimize the risk of pesticide resistance by limiting pesticide use and by trying to manage pests rather than trying to eradicate them. Our recent paper provides a small “stone” for the emerging “building” of a similar approach – adaptive therapy – that aims to improve the way use antimicrobial and anticancer drugs: https://www.pnas.org/content/early/2020/07/10/2003132117

Please check out this wonderful blog post by Maria O’Hanlon discussing our work and this emerging new trend in more sustainable drug application: https://bit.ly/3fs45sr

New research brings us closer to understanding the origin of the eukaryotic cell

A new study by Yale scientists provides an insight into a milestone event in the early evolution of life on Earth – the origin of the cell nucleus. Dating back to around 2.5 billion years ago, the origin of the nucleus enabled the transformation of relatively simple organisms, such as bacteria, into more sophisticated ones that ultimately gave rise to modern animals, plants, and fungi. The details of this key event have remained elusive for many years. This is because not a single transitional fossil has been found to date that could point to any intermediate stages, or the logic underlying this massive transformation that took place among living cells, all that time ago.

A study led by Dr. Sergey Melnikov, from the Dieter Soll Laboratory (Department of Molecular Biophysics and Biochemistry at Yale University), has finally found these missing fossils. Yet they were found not in clay or rocks but inside currently living cells, known as Archaea – the organisms that are believed to most closely resemble the ancient intermediates between bacteria and the more complex cells that we now know as eukaryotic cells. These transitional forms are nothing like the traditional fossils we think of, such as dinosaur bones deposited in the ground or insects trapped in amber. Known as ribosomal proteins, these particular transitional forms are about 100-million times smaller than our bodies. Melnikov and his colleagues discovered that ribosomal proteins can be used as living “molecular fossils”, whose ancient origin and structure structure may hold the key to understanding the origin of the cell nucleus.

“Simple lifeforms, such as bacteria, are analogous to a studio apartment: they have a single interior space which is not subdivided into separate rooms or compartments. By contrast, more complex organisms, such as fungi, animals, and plants, are made up of cells that are separated into multiple compartments,” explained Melnikov. “These compartments are connected to one another via microscopic ‘doors’ and ‘gates’; to pass through these doors and gates, the molecules that inhabit living cells carry special IDs, some of which are called nuclear localization signals, or NLSs.”

In attempting to find and analyze NLSs in ribosomal proteins from virtually all known organisms that inhabit our planet, Melnikov and colleagues have discovered that these special IDs are present not only in complex cells but also in Archaea – the relatively simple organisms whose cells lack internal compartments linked by subcellular doors and gates. The logical question which then arose was: what was the original biological function of these IDs?

“If you think about an equivalent to our discovery in the macroscopic world, it is similar to discoveries made during the last century of bird-like dinosaurs such as Caudipteryx zoui. An example of these ancient flightless birds has illustrated that it took multiple millions of years for dinosaurs to develop wings. Yet, strikingly, for the first few million years their wings were not good enough to support flight. This fact led to fierce debates about what the evolutionary advantage was in having these seemingly useless yet complex and costly ‘half-wings’. Also, what was the driving force behind the gradual development of wings in dinosaurs, if for most of this time these wings were unable to support flight? Our discovery raised similar questions about the origin of the cell nucleus: why did the IDs that allow movement between different cell compartments initially emerge in cells that were devoid of compartments? And what was the original biological function of these IDs in non-compartmentalized cells?”

In fact, studies of bird-like dinosaurs have suggested that even though half-wings could not support flight, they could support flight-like locomotion, such as gliding and accelerated climbing, suggesting that the advantage offered by gliding and climbing (and not flight itself) was the initial driving force behind the evolution of wings. Similarly, the study by Melnikov and colleagues suggests that, even though NLSs may not initially have emerged to allow cellular molecules to pass through microscopic gates between cellular compartments, they could have emerged to fulfill a similar biological function – to help molecules get to their biological partners. As Melnikov explains: “Our analysis shows that in complex cells the very same IDs that allow proteins to pass through the microscopic gates are also used to recognize biological partners of these proteins. In other words, in complex cells the IDs fulfill two conceptually similar biological functions. In the Archaea, however, these IDs play just one of these functions – these IDs, or NLSs, help proteins to recognize their biological partners and distinguish them from the thousands of other molecules that float in a cell.”

So what was the initial trigger that led to the evolution of these IDs among cellular proteins? As Melnikov explains, “When life first emerged on the face of our planet, the earliest life forms were likely made of a very limited number of molecules. Therefore, it was relatively easy for these molecules to find one specific partner among all the other molecules in a living cell. However, as cells grew in size and complexity, it is possible, even probable, that the old rules of specific interactions between cellular molecules had to be redefined, and this is how the IDs were introduced into the structure of cellular proteins – to help these proteins identify their molecular partners more easily in the complex environment of a complex cell. Coming back to the analogy with bird-like dinosaurs, our study illustrates the remarkable similarity between how evolution happens in the macroscopic world and how evolution happens in the world that Darwin never saw – the world of invisible molecules that inhabit living cells.”

More about the work:
https://academic.oup.com/mbe/advance-article-abstract/doi/10.1093/molbev/msz207