I’m looking at hundreds of millions of years in protein past with Alpha Fold and looking to learn about the beginning of life itself
Pedro Bertrao is a geneticist from ETH Zurich in Switzerland. He shares the story of the Alphafold.
As a scientist, I am interested in our differences.
More specifically, I am interested in how these differences arise. There are many people about how changes in DNA lead to changes in our traits, such as predispositions to certain diseases, or whether some people are taller than others, but our research is examining why that happens.
Ultimately, what we want to have is a model that accurately conveys how a person changes or the traits they have when carrying mutations at a particular location in the DNA.
There’s a long way to go to build it.
The first layer involves finding which mutations in the DNA do not cause any changes. To do that, you have to ask: Does it affect proteins? Next, we need to know how it works and how such functions exist, as proteins work together. This could mean that it depends on whether you are considering brain cells, kidney cells, or skin cells. Of course, each organ is different. There are many progressions and variables that can help you come up with proteins, groups of proteins, the cell tissue itself, and how the whole organism works from a single mutation.
Before the Alphafold, there were several protein structures in both individual proteins and complexes. For example, about 5% of interacting pairs had known structures, for example. Now this is changing rapidly. Furthermore, we now have an exciting opportunity to study the evolution of proteins in the origin of life.
I think this part of our research is particularly exciting. When you want to go back in time to see evolution, the way to do this is to compare sequences between proteins of different species. By doing that, you can try to guess what that sequence looks like in the evolutionary past.
Without the protein structure, we can go back to the past. There is a point where you lose confidence in what things look like hundreds of millions of years ago. Using alphafolds to compare the 3D shapes of proteins, they retain a long signal, as the 3D structure of the protein is preserved longer than the sequence encoding the shape.
As a result, we can track protein evolution over long periods of evolutionary timescales, and by looking at what proteins look like over the last hundred million years, we are more likely to infer what the earliest ancestral cells look like.
In many cases, science has these accumulations of progressive changes that accumulate over time, or slowly evolve over time. And often, you have a time of transformation. There is no doubt that Alphafold caused an era of transformation. It’s incredibly exciting. Now we have the opportunity to learn more about human biology and the origins of life itself.
