The Evolution of Human Cells in Terms of Protein Innovation

Abstract

Humans are composed of hundreds of cell types. As the genomic DNA of each somatic cell is identical, cell type is determined by what is expressed and when. Until recently, little has been reported about the determinants of human cell identity, particularly from the joint perspective of gene evolution and expression. Here, we chart the evolutionary past of all documented human cell types via the collective histories of proteins, the principal product of gene expression. FANTOM5 data provide cell-type–specific digital expression of human protein-coding genes and the SUPERFAMILY resource is used to provide protein domain annotation. The evolutionary epoch in which each protein was created is inferred by comparison with domain annotation of all other completely sequenced genomes. Studying the distribution across epochs of genes expressed in each cell type reveals insights into human cellular evolution in terms of protein innovation. For each cell type, its history of protein innovation is charted based on the genes it expresses. Combining the histories of all cell types enables us to create a timeline of cell evolution. This timeline identifies the possibility that our common ancestor Coelomata (cavity-forming animals) provided the innovation required for the innate immune system, whereas cells which now form the brain of human have followed a trajectory of continually accumulating novel proteins since Opisthokonta (boundary of animals and fungi). We conclude that exaptation of existing domain architectures into new contexts is the dominant source of cell-type–specific domain architectures.

Promoter Architecture and Sex-Specific Gene Expression in Daphnia pulex

“…Kimura et al (2006) propose that alternative promoters lead to alternative first exon usage, which contributes to proteome diversity. Using the panel of CAGE data in human cell lines generated by FANTOM5 [FANTOM Consortium and the RIKEN PMI and CLST (DGT) 2014], Sardar et al (2014) presented evidence in support of this hypothesis, demonstrating that alternative promoter usage causes putative inclusion or exclusion of entire domains in the amino termini of proteins. While this hypothesis is enticing, its drawback is the relative lack of transcript connectivity evidence; in nearly all circumstances each CAGE peak is informatically connected to a downstream gene body, thus, (+1) is identified by the blue arrow, and the TATA consensus sequence is represented by the red rectangle.…”

Origins and structural properties of novel andde novoprotein domains during insect evolution

“…Most proteins can be defined by a list of domains corresponding to a domain architecture or domain arrangement, linked by unstructured amino acid sequences [7]. Changes in the repertoire of domain arrangements can be used to quantify divergence between organisms [8,9] and are often linked to novel traits and adaptation [10][11][12][13][14][15][16][17][18].…”

Evolutionary Cell Biology of Proteins from Protists to Humans and Plants

“…What previously had been considered as pre‐adaptation is now called “exaptation,” that is, a shift in function of a trait/molecule during evolution (Sardar et al. ). Exaptation is now considered an important mechanism in evolution.…”

“…Neofunctionalization and refunctionalization mean establishment of an essentially new function for a newly evolved protein and reassignment of a new function to an already existing type of protein, respectively. What previously had been considered as pre-adaptation is now called "exaptation," that is, a shift in function of a trait/molecule during evolution (Sardar et al 2014). Exaptation is now considered an important mechanism in evolution.…”