AUTHOR=Williams Donnell L. , Sikora Veronica Maria , Hammer Max A. , Amin Sayali , Brinjikji Taema , Brumley Emily K. , Burrows Connor J. , Carrillo Paola Michelle , Cromer Kirin , Edwards Summer J. , Emri Olivia , Fergle Daniel , Jenkins M. Jamal , Kaushik Krishangi , Maydan Daniella D. , Woodard Wrenn , Clowney E. Josephine TITLE=May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.720798 DOI=10.3389/fcell.2021.720798 ISSN=2296-634X ABSTRACT=

How does the information in the genome program the functions of the wide variety of cells in the body? While the development of biological organisms appears to follow an explicit set of genomic instructions to generate the same outcome each time, many biological mechanisms harness molecular noise to produce variable outcomes. Non-deterministic variation is frequently observed in the diversification of cell surface molecules that give cells their functional properties, and is observed across eukaryotic clades, from single-celled protozoans to mammals. This is particularly evident in immune systems, where random recombination produces millions of antibodies from only a few genes; in nervous systems, where stochastic mechanisms vary the sensory receptors and synaptic matching molecules produced by different neurons; and in microbial antigenic variation. These systems employ overlapping molecular strategies including allelic exclusion, gene silencing by constitutive heterochromatin, targeted double-strand breaks, and competition for limiting enhancers. Here, we describe and compare five stochastic molecular mechanisms that produce variety in pathogen coat proteins and in the cell surface receptors of animal immune and neuronal cells, with an emphasis on the utility of non-deterministic variation.