Evolutionary Characteristics of Missing Proteins: Insights into the Evolution of Human Chromosomes Related to Missing-Protein-Encoding Genes

Although
the “missing protein” is a temporary concept
in C-HPP, the biological information for their “missing”
could be an important clue in evolutionary studies. Here we classified
missing-protein-encoding genes into two groups, the genes encoding
PE2 proteins (with transcript evidence) and the genes encoding PE3/4
proteins (with no transcript evidence). These missing-protein-encoding
genes distribute unevenly among different chromosomes, chromosomal
regions, or gene clusters. In the view of evolutionary features, PE3/4
genes tend to be young, spreading at the nonhomology chromosomal regions
and evolving at higher rates. Interestingly, there is a higher proportion
of singletons in PE3/4 genes than the proportion of singletons in
all genes (background) and OTCSGs (organ, tissue, cell type-specific
genes). More importantly, most of the paralogous PE3/4 genes belong
to the newly duplicated members of the paralogous gene groups, which
mainly contribute to special biological functions, such as “smell
perception”. These functions are heavily restricted into specific
type of cells, tissues, or specific developmental stages, acting as
the new functional requirements that facilitated the emergence of
the missing-protein-encoding genes during evolution. In addition,
the criteria for the extremely special physical–chemical proteins
were first set up based on the properties of PE2 proteins, and the
evolutionary characteristics of those proteins were explored. Overall,
the evolutionary analyses of missing-protein-encoding genes are expected
to be highly instructive for proteomics and functional studies in
the future.