Image by Alva et al (CC BY 4.0)

Piecing together the evolution of proteins

Comparisions of modern proteins provides new clues as to how the first proteins may have emerged billions of years ago.

Life as we know it today is largely the result of the chemical activity of proteins. Much research suggests that the ancestors of most modern proteins were already present in the ‘Last Universal Common Ancestor’, a theoretical ancient organism from which all life on earth descended and which lived around 3.5 billion years ago.

Today, related versions of these ancestral proteins are found in organisms as different as bacteria, humans and plants. While they seem highly diverse, these proteins were all assembled from only a few thousand modular units, termed domains. However, it is not clear how the first domains emerged.

Previously, in 2001 and 2003, researchers hypothesized that the first protein domains arose by joining and swapping short lengths of proteins called peptides that had emerged before there were living cells on earth — a time that is often called the “RNA world”. Now, Vikram Alva and colleagues — including the researchers involved in the 2003 work — have attempted to detect remnants of these ancient peptides in modern proteins.

Alva and colleagues first compared modern proteins in a way that is similar to how linguists have compared modern languages to reconstruct ancient vocabularies. This revealed 40 fragments that occur in seemingly unrelated proteins, but are very similar in their sequence and structure. These fragments are commonly found in what are likely the oldest observable proteins, and are involved in the activities that are most fundamental to life (for example, binding to DNA and RNA). This led Alva and colleagues to propose that these fragments represent the observable remnants of a primordial “RNA-peptide world”.

The hypothesis that proteins evolved from peptides provides a number of predictions that can be tested in experiments. These fragments open avenues to explore in the laboratory the origin of modern proteins and to build new proteins not seen in nature.

To find out more

Read the eLife research paper on which this eLife digest is based: “A vocabulary of ancient peptides at the origin of folded proteins” (December 14, 2015).
eLife is an open-access journal for outstanding research in the life sciences and biomedicine.
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