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Updated: Mar 24, 2026

A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing

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Published on: July 3, 2016

The Jackprot Simulation Couples Mutation Rate with Natural Selection to Illustrate How Protein Evolution Is Not

Guillermo Paz-Y-Miño C¹, Avelina Espinosa², Chunyan Y Bai³

¹Department of Biology, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, MA 02747-2300, USA.

Evolution

|March 15, 2016

Summary

Protein evolution is not random. Natural selection guides molecular improvements, as demonstrated by the "jackprot" simulation, showing faster evolution than chance alone for complex ion channels.

Keywords:

Design creationism Ion channels Jackacid Jackdon Molecular evolution

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Area of Science:

Molecular Biology
Evolutionary Biology
Biophysics

Background:

Protein evolution is often mistakenly viewed as a random process.
Previous models failed to adequately explain the complexity and adaptive nature of proteins.
Ion channels, crucial for cellular function, present a complex structure requiring explanation.

Purpose of the Study:

To demonstrate that protein evolution is a directed process, not random.
To model the interplay between mutation rate and natural selection in protein evolution.
To provide a didactic tool illustrating the evolution of complex ion channels.

Main Methods:

Utilized slot-machine probabilities and ion channel structure to illustrate biological directionality.
Developed a computer program and online interface, "The Jackprot Simulation," to model polypeptide evolution.
Contrasted random DNA sequence generation with a selection-driven scenario ('jackprot') for KcsA potassium channel evolution.

Main Results:

The 'jackprot' scenario predicted significantly faster evolution than random chance.
Cumulative selection at codon positions ('jackdons') led to the highest-fitness peptide sequence ('jackprot').
The simulation demonstrated that mutation rate coupled with natural selection explains specialized protein evolution.

Conclusions:

Protein evolution is a directed process, guided by natural selection retaining adaptive sequences.
The 'jackprot' model effectively illustrates how complex proteins like ion channels evolve.
This work refutes creationist claims of design and supports a scientifically grounded understanding of molecular evolution.