Animal Cell Differentiation Patterns Suppress Somatic Evolution

Cell differentiation in multicellular organisms has the obvious function during development of creating new cell types. However, in long-lived animals with extensive cell turnover, cell differentiation often continues after new cell types are no longer needed or produced. Here we address the question of why this is true. It is believed that multicellular organisms could not have arisen or been evolutionarily stable without possessing mechanisms to suppress somatic selection among cells within organisms, which would otherwise disrupt organismal integrity. Here we propose that one such mechanism is a specific pattern of ongoing cell differentiation commonly found in metazoans with cell turnover, which we term “serial differentiation”. This pattern involves a sequence of differentiation stages; starting with self-renewing somatic stem cells and proceeding through several (non-self- renewing) transient amplifying stages before ending with terminally differentiated cells. We test this hypothesis using an agent-based computer simulation of cell population dynamics and evolution within tissues. The results indicate that, relative to other, simpler patterns, tissues organized into serial differentiation experience lower rates of detrimental cell-level evolution. Self-renewing cell populations are susceptible to somatic evolution, while those that are not self-renewing are not. We find that a mutation disrupting differentiation can create a new self-renewing cell population that is vulnerable to somatic evolution. These results are relevant not only to understanding the evolutionary origins of multicellularity, but also the causes of pathologies such as cancer and senescence in extant metazoans including humans.