Gene Duplication and Alternative Splicing as Evolutionary Drivers of Proteome Specialization

Animals comprise hundreds of cell types, each with specialized biological functions. However, many genes expressed in each cell type belong to widely conserved gene families with ancestrally ubiquitous expression. This raises a paradox: how have these genes evolved to shape cell type-specific traits without compromising their ancestral function in all other cells? This can be achieved through gene duplication and the origin of regulated, alternatively spliced exons, which generate new related proteins in the form of paralogous genes and alternative isoforms, respectively. Here, we explore how such new related proteins can contribute to the evolution of specific cell types while preserving broader ancestral roles. Specifically, we separately classify possible expression and functional fates for new related proteins and discuss their interplays and evolutionary likelihood. Our primary hypothesis is that expression specialization, mostly coupled with functional specialization, is the predominant fate for both paralogous genes and alternative isoforms throughout animal evolution.