[4] The process of neofunctionalization begins with a gene duplication event, which is thought to occur as a defense mechanism against the accumulation of deleterious mutations.
[6] It is much more rare to see major changes in protein function, such as subunit structure or substrate and ligand affinity, as a result of neofunctionalization.
The first reason is that functional changes typically require a large number of amino acid changes; which has a low probability of occurrence.
[11] In 1970, Ohno suggested that neofunctionalization was the only evolutionary mechanism that gave rise to new gene functions in a population.
[6] Today, subfunctionalization is a widely accepted alternative fixation process for gene duplicates in the population and is currently the only other possible outcome of functional divergence.
The evolution of the antifreeze protein in the Antarctic zoarcid fish Lycodichthys dearborni provides a prime example of neofunctionalization after gene duplication.
After duplication one of the paralogs began to accumulate mutations that lead to the replacement of SAS domains of the gene allowing for further development and optimization of the antifreeze functionality.
These five classes of vertebrate visual opsins emerged through a series of gene duplications beginning with LWS and ending with Rh1.