Protein Space and the Protein Universe: Introduction

Evolution is easier than we think, and one great way to see why is to look at what we know about protein evolution.

Proteins have been evolving on our planet for about 4 billion years. Their appearance almost certainly precedes the beginning of life itself. We still don't know how the whole thing got off the ground, but once the stage was set (in living cells), evolution began exploring Protein Space. As it did so, it slowly created the Protein Universe. Since these two concepts — Protein Space and the Protein Universe — are so central to understanding and picturing protein evolution, we should carefully define what they mean.

Contemplating libraries in biology. Not that kind. Not that one either.

What is a library? If you ask a biologist (especially a molecular biologist) this question, they are likely to ask for clarification. In their work, they are likely to make regular use of two very different kinds of libraries.

The first is the kind that we've had for millenia: a collection of books, journals, and media that is ordered and curated by people. These are the OG libraries, with 'book' at the very root of the word. They're rapidly evolving in our digital world, but I think they are still essentially what they've always been. Your friend the molecular biologist may not regularly go to a separate room or building to find materials, but they will use the library often.

The second is an extension of the OG concept of a library, but is still called a 'library' by your friend. It contains information, perhaps in vast amounts, but is not ordered or curated. Crucially, it is a specific collection of a particular type of information: genetic information. And while it's neither ordered nor curated, it is physical, and is designed to be searched. The contents of the library might be DNA sequences (genes or even just chunks of some interesting genome) or protein sequences. Unlike your favorite public library, this one doesn't come with a search feature: you have to do that yourself. The process of searching a library is called screening. Your molecular biologist friend can go to the institutional library to read about these kinds of libraries, and find techniques on how to screen one, then perhaps go to a colleague or a vendor to obtain a library. Or she will obtain tools to make one herself.

In my previous post, I talked of an even more radical extension of the concept of a library: a collection of all the versions of any kind of text (a book, a genome, a set of proteins).

The library of possible proteins is beyond vast. Does this cause us to view evolution as harder than it is?

Bates Hall at the Boston Public Library

One of the most effective metaphors for evolutionary change is the image of an exploration of a space, perhaps a map that shows "fitness peaks" or, better, a library of possibilities. The philosopher Daniel Dennett, writing in Darwin's Dangerous Idea, suggested The Library of Mendel as a way of thinking about the total set of possible gene sequences. He was adapting an idea famously employed in a short story by Jorge Luis Borges called "The Library of Babel," which consists of the total set of possible books of a particular length. (This "library" exists on a website designed for creators and researchers.)

Contemplating a space of possibilities—whether that space consists of books written in English (26 letters), or "books" written in the language of DNA (four letters), or "books" written in the language of protein (20 letters)—is both fun and dizzying. The dizziness is induced (for me, at least) by the vastness of these libraries (Babel or Mendel, doesn't matter). How vast? Here is how Dennett describes the Library of Babel's size (italics are his):

No actual astronomical quantity (such as the number of elementary particles in the universe, or the amount of time since the Big Bang, measured in nanoseconds) is even visible against the backdrop of these huge-but-finite numbers. If a readable volume in the Library were as easy to find as a particular drop in the ocean, we'd be in business!

—Darwin's Dangerous Idea, p. 109

Dennett then uses Vast to indicate "Very-much-more-than-astronomically" large and Vanishingly small to indicate the likelihood of something like discovering a "volume with so much as a grammatical sentence in it" in the Library. In other words, we lack words to adequately describe the size of the Library and the improbability of randomly discovering anything coherent inside it.

Exploring the protein universe: a response to Doug Axe

One of the goals of the intelligent design (ID) movement is to show that evolution cannot be random and/or unguided, and one way to demonstrate this is to show that an evolutionary transition is impossibly unlikely without guidance or intervention. Michael Behe has attempted to do this, without success. And Doug Axe, the director of Biologic Institute, is working on a similar problem. Axe's work (most recently with a colleague, Ann Gauger) aims (in part, at least) to show that evolutionary transitions at the level of protein structure and function are so fantastically improbable that they could not have occurred "randomly."

Recently, Axe has been writing on this issue. First, he and Gauger just published some experimental results in the ID journal BIO-Complexity. Second, Axe wrote a blog post at the Biologic site in which he defends his approach against critics like Art Hunt and me. Here are some comments on both.