Jacob was convinced that although morphological analysis supports his notion of
bricolage, one would find more evidence of tinkering at the
molecular level. The tinkering model suggests that the
genes of the earliest organisms were very short, and all subsequent genes were formed by
duplication, combination, and reassorting these original sequences. It is well established that gene duplication has produced a great deal of diversity throughout evolutionary history. One example of molecular tinkering can be found in
mitochondrial nucleoproteins, some of which originate from
eukaryotes; in this case, the tinkerer used whatever tools were at her disposal, including materials from an entirely different
taxonomic domain. To understand molecular tinkering, it is important to grasp the concept of a
protein domain, which is a distinct region of a
protein that has a defined shape, which determines the function of the protein. There are many different means by which tinkering can result in molecular and
phenotypic novelty, primarily by taking apart the Lego blocks of proteins and putting them together again in unique patterns. Generally, these processes add to the organizational complexity of the
genome, the
proteome, or both. Eukaryotic genes have undergone frequent internal gene duplication throughout evolutionary history. One example is seen in the dinucleotide-binding regions of glyceraldehyde 3-phosphate dehydrogenase and alcohol dehydrogenase: the duplicated domain is capable of binding with more molecules than the unduplicated. Most domains only have a small number of uses, while very few domains are used as Lego blocks over and over again in multidomain proteins. Phenotypic innovation does not arise solely from the creation of new proteins, but also from changing gene expression and
protein-protein interactions. One example of novelty associated with domain shuffling is multicellularity. Gene fusion (the creation of a
fusion gene by joining two genes together) and gene fission or fragmentation, which results in splitting one gene with many domains into multiple smaller genes, are the other two molecular mechanisms by which mosaic proteins can be formed.
Alternative splicing Alternative splicing is another mechanism of molecular tinkering that may be responsible for increasing diversity in the proteome. One special kind of alternative splicing is
nested genes, which produce intron-encoded proteins. It has been proposed that nested gene structures could be maintained via neutral processes according to the
neutral theory of evolution.
De novo evolution of protein-coding genes from non-coding DNA De novo gene birth is very rare. The most probable path from noncoding DNA to a protein-coding gene is to first become a
protogene, similar to how functional genes first become
pseudogenes before becoming completely
nongenic. Although they are too rare to notably increase the number of proteins in a given lineage, the tinkering model posits that adding just a few Lego blocks to the collection allows for many new possible combinations of domains, i.e., proteins with new shapes and functions.
Exonization of introns and pseudoexonization of exons Exonization is a very rare phenomenon in which an intron becomes an exon. In pseudoexonization, an exon becomes nonfunctional; this in turn changes the shape and function of the protein.
Gene loss and unitary pseudogenes When
selective constraints disappear, it is possible for genes to be lost via one of two mechanisms. The first is deleting a single-copy gene. The second is
nonfunctionalization of a single-copy gene; this produces a unitary
pseudogene, which has no functional paralogs, is comparable to
vestigial anatomical structures, and is uncommon due to its often deleterious nature. In the rare case that gene loss becomes fixed in a
population, it is difficult to definitively say what was the cause. == References ==