Evidence Record

Changes in Protein Function

Protein Innovation  •  Biological Innovation and Evolutionary Mechanisms
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Mutations can alter protein activity, specificity, stability, regulation, and interactions. Experimental studies allow researchers to trace some pathways between related protein functions.

The Investigative Question

How readily can existing proteins acquire different or expanded functions?

What We Observe

Proteins often tolerate some sequence changes while retaining function. Other mutations alter activity, binding, stability, specificity, or regulation. Experiments show that mutations can substantially increase weak secondary or promiscuous activities already present in a protein, sometimes allowing those activities to become increasingly specialized.

Scientific Background

Protein evolution can be studied through comparative sequences, ancestral reconstruction, mutagenesis, directed evolution, and laboratory selection.

Why It Matters

New protein functions are central to biological innovation because cellular structures and pathways depend upon proteins performing specific tasks and interacting with other components.

What Is Known

Protein functions can change through mutation. Laboratory studies have documented shifts in substrate specificity, catalytic activity, stability, regulation, and molecular interactions. Experiments also show that weak secondary activities can provide starting points from which mutations produce substantially increased activity toward a different substrate or function.

What Is Proposed

Evolutionary models propose several pathways toward altered protein functions. These include modification of weak secondary activities, gene duplication followed by divergence, recruitment of existing molecular interactions, and successive mutations that alter activity or specificity.

What Remains Uncertain

Experimental accessibility varies greatly among proteins. Demonstrating a pathway between related functions does not automatically establish the historical pathway for every protein family. The starting activity, number and order of mutations, effects on other functions, and availability of selectable intermediate states must be examined in particular cases.

Design Relevance

Intelligent Design discussions often focus on whether functional proteins are accessible through undirected sequence change. Experimental studies of actual proteins provide a way to investigate that question directly.

Assessment

Existing proteins can acquire substantially altered functions. Experimental studies demonstrate changes in activity and specificity and show that pre-existing secondary activities or molecular interactions can provide starting points for further change. The scale of the change, the starting function, the number and order of mutations required, and the availability of selectable intermediates should therefore be examined in specific cases.

Research Sources

Aharoni et al. — Evolvability of Promiscuous Protein Functions
Amir Aharoni; Leonid Gaidukov; Olga Khersonsky; Stephen McQ Gould; Cintia Roodveldt; Dan S. Tawfik • Nature Genetics • 2005
Use: Experimental Evidence
Relevance: Provides direct experimental evidence that mutations can substantially alter weak secondary activities of existing proteins while preserving much of their native activity.
DOI: 10.1038/ng1482
Bridgham et al. — Evolution of Hormone-Receptor Complexity
Jamie T. Bridgham; Sean M. Carroll; Joseph W. Thornton • Science • 2006
Use: Ancestral Reconstruction
Relevance: Uses ancestral protein reconstruction and experimental testing to investigate historical changes in steroid receptor function and specificity.
DOI: 10.1126/science.1123348
Yuan et al. — Laboratory-Directed Protein Evolution
Ling Yuan; Itzhak Kurek; James English; Robert Keenan • Microbiology and Molecular Biology Reviews • 2005
Use: Scientific Foundation
Relevance: Provides a broad review of laboratory evidence showing that mutation, recombination, selection, and screening can alter protein properties and functions.
DOI: 10.1128/MMBR.69.3.373-392.2005