In the Absence of DNA, Did Heat Cause the First Cells To Divide?

Without genetic material, how did the earliest cells divide? A new theoretical model proposed by researchers at the Palais de la Découverte in Paris suggests that heat might have been the driving force. The study is published in Biophysical Journal.

Regulated cell division is important

The cells of your body are like mini molecular factories. Day and night, they encapsulate the vast array of biological and chemical reactions that are required for you to function as a human. These processes are beautifully orchestrated by biology – you don't even have to think about them, they are the silent workings of your existence.

The regulation of cells – how they grow and divide – is important for their correct function and survival. In conditions such as cancer, we see how accelerated cell division can lead to disease. It is therefore important for scientists to understand the complex network of synchronized processes that drive cell division and how they have evolved. While researching in this space, a research group from Universcience created a model that proposes how protocells – the ancestors of modern cells – divided.

Meet LUCA and FUCA

When we trace the ancestry of living organisms that inhabit our planet today, be it humans, animals, plants, fungi and algae, we all have a common ancestor. "Our Last Unicellular Common Ancestor – or "LUCA" – was a cell that already contained DNA and probably a paraphernalia of enzymes and other proteins," explained Romain Attal, project manager at Palais de la Découverte. LUCA was the product of a chemical evolution of several million years; so, what processes were responsible for reproduction prior to LUCA?

To answer this question, we must go further back in time, to the very beginnings of life on Earth, around 3.8 - 4 million years ago. "Before that, during the Hadean eon, the physical conditions of our planet were too hostile for any imaginable form of life. The oldest fossils known today (stromatolites) are about 3.8 billion years old," Attal said. "This means we have around 200 million years of time between abiotic matter to the first known cells."

Protocells are similar to the first unicellular common ancestor, or FUCA. FUCA is, as Attal described, is the grand-grand-grand (and so on) mother/father of LUCA.

Protocells comprise a vesicle that is bound by a membrane bilayer and has a primeval form of metabolism inside. Attal and colleagues postulate that, due to the fact they did not possess genetic material or organelles, protocells must have adopted a very simple mechanism to reproduce. What was this mechanism? "A protocell must be able to reproduce before the emergence of complex molecules (RNA, enzymes, cytoskeleton etc.). Therefore, the ability to split a protocell into two daughter protocells must be a purely physical process, Attal said.  

Hot then you're cold

The physical process, Attal and colleagues propose in their paper, was temperature difference. "Life is a complex network of intertwined irreversible physical and chemical processes. A general setting for the study of such processes is provided by non-equilibrium thermodynamics […] In short, these processes are described by 'currents' (of molecules, of heat, of electricity, ...) and 'forces' (differences of concentrations, of temperature, of electrical potential and so on."

Attal said. The relations of the currents are supposed to be linear, and thus can be written in the following equation

Currents = conductance x force

"This is a generalization of Ohm's law (electric current = conductance x electric tension) taught in high school," added Attal. In this equation, among the forces, there are differences in temperature between the interior and the exterior of the protocell's vesicle. The gap in temperature induces a heat current that moves from the hot inside to the cooler outside.

"We propose that this temperature difference is an important driving force that can help the vesicle to split. The membrane of the vesicle is a bilayer made of amphiphilic molecules. If the inner leaflet (L_in) of this bilayer is hotter than the outer leaflet (L_out), the hottest molecules can go from L_in to L_out more easily than cold molecules can go from L_out to L_in," Attal described. The asymmetric nature of this current forces the outer leaflet of the protocell to grow at a faster rate than the inner leaflet, curving the surface of the vesicle until it splits.

Rethinking the central dogma of biology

The model is purely theoretical and, unfortunately, protocells did not leave any fossils behind. But Attal thinks that it might be possible to recreate them in a laboratory environment: "We could encapsulate some fluorescent molecules inside tiny vesicles and illuminate them with visible light. If these molecules radiate in the infrared domain, the inside of the vesicle will heat up gradually, thus creating a gradient of temperature with respect to the outside," he said. The challenge here would be to select the correct membrane molecules and fluorescent molecules. Attal joked that, as a "non-experimentalist" he will hand over this conundrum to those that study real vesicles in the laboratory.

This work is an invitation for other research groups to reconsider the basic dogma of cell biology, which states that cells cannot function as thermal machines due to the need for their temperature to be uniform. "We propose the opposite hypothesis, that temperature gradients ARE important in cell biology. More generally, the biological processes are triggered and guided by simple physical forces, and life itself is an ineluctable phenomenon based on the laws of physics," said Attal.

"Experimentally, we would like our model to enrich the various approaches of the origin of life, and to provide a new look at cancer. This complex illness, characterized by an uncontrolled cell proliferation, might be caused by simple physical forces," he concluded.

Reference: Attal R and Schwartz L. Thermally driven fission of protocells. Biophysical Journal. 2021. doi: 10.1016/j.bpj.2021.08.020.