Micro-to multi-chimerism: the multiple facets of a singular phenomenon

Natural chimeras are prevalent in nature (> 10 phyla of protists, plants, invertebrates, and vertebrates), disrupting the conventional believe that genetically homogeneous entities are selected to prevent conflicts within an organism. Chimerism emerges as a significant ecological/evolutionary mechanism, shaping the life history characteristics of metazoans, and it develops in various forms, one of which is called 'microchimerism'. Furthermore, chimerism is a pivotal phenomenon, presenting complex biological and ecological expressions akin to a "double-edged sword", bypassing both innate and adaptive immune responses. Considering the proportionate contribution of chimeric partners and their spatial arrangements within chimeras, unveils six somatic states of chimerism (purged-chimerism, sectorial-chimerism, mosaic-chimerism, mixed-chimerism, microchimerism and multi-chimerism) and three states of germline chimerism (mixed-chimerism, male/female chimerism and parasitic germline chimerism). These diverse chimeric states are categorized into two distinct series of continua, namely 'somatic cell chimerism' and 'germline chimerism' scenarios where dynamic chimeric states transit into other states, and vice versa, within a specific continuum that relies on the concept of an endless 'Escherian stairwell' of chimerism states. Also, the same chimera may portray simultaneously, different chimeric states in various parts/organs. We further reviewed the evolutionary perspectives for chimerism, raising five commonly shared features of chimerism (multichimerism, ontogenic windows, reproductive chimerism, transmissible chimerism, germline hitchhiking) and 'costs' and 'benefits' accrued to chimerism, shared between invertebrates and vertebrates, including humans. We contest that 'microchimerism' lacks any quantitative definition, represents just a single facet in the multi-facet panorama of chimeric phenomena that demonstrate transitions over time into other states. All of the above carry evolutionary and clinical implications.