Integrating the Study of Polyploidy Across Organisms, Tissues, and Disease

Abstract

Polyploidy is a cellular state containing more than two complete chromosome sets. It has largely been studied as a discrete phenomenon in either organismal, tissue, or disease contexts. Increasingly, however, investigation of polyploidy across disciplines is coalescing around common principles. For example, the recent Polyploidy Across the Tree of Life meeting considered the contribution of polyploidy both in organismal evolution over millions of years and in tumorigenesis across much shorter timescales. Here, we build on this newfound integration with a unified discussion of polyploidy in organisms, cells, and disease. We highlight how common polyploidy is at multiple biological scales, thus eliminating the outdated mindset of its specialization. Additionally, we discuss rules that are likely common to all instances of polyploidy. With increasing appreciation that polyploidy is pervasive in nature and displays fascinating commonalities across diverse contexts, inquiry related to this important topic is rapidly becoming unified.

Keywords: cancer; development; evolution; polyploidy; stress; whole-genome duplication.

Figure 1

Terminology, generation, and occurrence of polyploidy. (a) The contrast between endopolyploidy and organismal polyploidy. A cell with one set of homologous chromosomes, drawn here with each having two sister chromatids, indicates diploid, while a cell with two sets of homologous chromosomes indicates tetraploid (a proxy for all polyploidy). (b) Mechanisms leading to polyploidy. Chromosomes denote diploid/polyploid as in panel a, while darkened circles indicate the presence of one or more nuclei in a cell. For unreduced gamete fusion, note that the illustration shows the union of two gametes, both of which are unreduced. (c) Organismal polyploidy across the tree of life. Shown are approximate occurrences of WGD events (yellow dots). This is by no means a comprehensive compilation of WGD across the tree of life, nor do the dots correspond to a point in time. Panel adapted from Reference with modifications by Stephen Smith. (d) Tissue polyploidy across animal organ systems. A pregnant human female is used to represent the prevalence of tissue polyploidy. Symbols (see key) indicate polyploidy arising during development, aging, stress, and in cancer. Although a human is used in the diagram, the symbols indicate polyploidy in the indicated organ system for at least one animal species. Abbreviations: SAR, clade of eukaryotes including stramenopiles, alveolates, and rhizarians; WGD, whole-genome duplication.

Figure 2

Emerging rules of polyploidy. (a) Polyploidy alters geometry and biological scaling. Pictured are two cells or organisms depicted as spheres: (left) one small diploid and (right) one large polyploid. Distinctly colored bumps on the sphere indicate changes in the distribution of molecules (in the case of a cell) or cells (in the case of an organism) on the surface of a cell or organism. (b) Polyploidy facilitates the exploration of genomic space. Simulated evolution of (upper) a diploid and (lower) a polyploid cell or organism over time. Colored bars on chromosomes indicate a genetic change of any kind (mutation, copy number change, etc.) to illustrate that polyploidy increases genetic change over time. Large focal changes (such as large duplications or deletions) are shown by changes in overall chromatid length.