Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics

Abstract

The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals’ unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue—normal and transformed—can also contribute the framework for exploring animal evolution.

Bioelectric Pharmacology of Cancer: A Meta-Analysis of Ion Channel Drugs Affecting the Cancer Phenotype

“…The fundamental nature of cancer has been approached from many perspectives, focusing on diverse aspects such as microenvironment, genomic damage, stress, game theory of cooperation and competition among cells, evolutionary processes, and disorders of multicellularity (Kenny et al 2007;Tarin 2012b;Tarin 2012a;Shiozawa et al 2013;Tarin 2013;Sonnenschein and Soto 2015;Wu et al 2015;Sonnenschein and Soto 2016;Stankova et al 2018;Valkenburg et al 2018;Amend et al 2019;Archetti and Pienta 2019;Jacques et al 2022;Truskowski et al 2023). One critical aspect is the breakdown of the normal mechanisms that keep individual cells harnessed toward largescale anatomical goals -the maintenance of complex tissues and organs -and a reversion to ancient unicellular behavioral policies (Rubin 1985;Lineweaver et al 2014;Davies and Agus 2015;Bussey et al 2017;Cisneros et al 2017;Levin 2019).…”