The mystery of protein superfamilies: How do these ancient organisms prove the existence of a common ancestor?

Proteins have been essential to the functioning of organisms throughout the history of life. Among these proteins that build the basis of life, the concept of superfamily provides an important perspective, revealing the common ancestral connection between organisms. In this article, you will explore the mysteries of protein superfamilies and learn how they demonstrate the connections between different organisms.

Definition of protein superfamily

Protein superfamily is defined as the largest group of proteins inferred based on a common ancestor. This inference of common ancestry is often made based on structural alignment and mechanistic similarity, even though in some cases there is no obvious sequence similarity between the proteins. Through these interconnections, scientists are able to piece together the evolutionary history of proteins and understand how they evolved into their present-day forms.

Methods for inferring common ancestry

When defining protein superfamilies, scientists use three main approaches: sequence similarity, structural similarity, and mechanistic similarity. These methods have their own advantages and can capture different levels of association between proteins.

Sequence Similarity

In most cases, the similarity between different amino acid sequences is a common method to infer homology. This sequence similarity often points to the possibility of gene duplication and evolutionary divergence. However, these approaches also face some limitations because different proteins may have undetectable sequence similarities during the long evolution process.

For example, in the PA class of proteases, no residues are conserved across the superfamily, not even those in the catalytic triad.

Structural similarity

Structure is more evolutionarily conserved than sequence. Many proteins with highly similar structures may have completely different amino acid sequences. By using structural alignment programs such as DALI, scientists can look at a protein's three-dimensional structure to find other proteins with similar folds. This approach can in some cases even identify homologies between proteins that are not detectable in sequence.

Mechanical similarity

The catalytic mechanism of an enzyme is generally conserved within a superfamily, although the substrate specificity may vary widely. Taking the PA class of proteases as an example, although the residues of the catalytic triad have undergone divergent evolution, all members use similar mechanisms to perform covalent nucleophilic catalysis on proteins, peptides, or amino acids.

The evolutionary significance of protein superfamilies

Protein superfamilies represent the limit of the common ancestors we can currently identify. They are the most ancient evolutionary groups inferred based on direct evidence. Members of some superfamilies occur in all kingdoms of life, suggesting that the last common ancestor of these superfamilies existed in the last common ancestor of all life (LUCA).

Diversification and structural conservatism

Most proteins contain multiple domains; in fact, 66-80% of eukaryotic proteins and approximately 40-60% of prokaryotic proteins have multiple domains. Over time, many of the domains have been intermingled to form the diverse protein superfamilies we have today.

Conclusion

Through the above discussion, we have identified protein superfamilies, which not only enriches our understanding of biological evolution, but also provides important clues for future research in life sciences. As technology advances, our understanding of proteins will deepen, leading us to uncover the deeper mysteries of life. In this context, have you ever wondered how many unsolved mysteries these ancient creatures have left for us in the long river of evolution?

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