Biology Principles

[Gualtar Pennington]

BiologicalPrinciples is an active-learning class that will introduce you to basic principles of modern biology, including evolution, ecological relationships, biomacromolecules, bioenergetics, cell structure, and genetics. This course will help you develop critical scientific skills that include hypothesis testing, experimental design, data analysis and interpretation, and scientific communication. Class time will include a variety of team-based activities designed to clarify and apply new ideas by answering questions, drawing diagrams, analyzing primary literature, and explaining medical or ecological phenomena in the context of biological principles. We will spend class time on building your comprehension of the material you find the most difficult, based on pre-class assessments.

This textbook is editorially agile to keep pace with the course as it develops. We craft content for readers carefully, and then seek reader feedback. If you see blue text while you read, that reflects text (or images) changed in real time during the semester to help you better work with and learn the course material.

The UN SDGs, or United Nations Sustainable Development Goals, are a set of 17 global goals that were adopted by all United Nations Member States as a universal call to action to end poverty, protect the planet, and ensure that all people enjoy peace and prosperity by 2030. The pages within this book have been deliberately connected to these goals to show the relevance of course content to solving real-world problems.

Biological Principles is an online, open education resource written and curated by faculty in the School of Biological Sciences at Georgia Tech and licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Groundbreaking research on the universality and diversity of microorganisms is now challenging the life sciences to upgrade fundamental theories that once seemed untouchable. To fully appreciate the change that the field is now undergoing, one has to place the epochs and foundational principles of Darwin, Mendel, and the modern synthesis in light of the current advances that are enabling a new vision for the central importance of microbiology. Animals and plants are no longer heralded as autonomous entities but rather as biomolecular networks composed of the host plus its associated microbes, i.e., "holobionts." As such, their collective genomes forge a "hologenome," and models of animal and plant biology that do not account for these intergenomic associations are incomplete. Here, we integrate these concepts into historical and contemporary visions of biology and summarize a predictive and refutable framework for their evaluation. Specifically, we present ten principles that clarify and append what these concepts are and are not, explain how they both support and extend existing theory in the life sciences, and discuss their potential ramifications for the multifaceted approaches of zoology and botany. We anticipate that the conceptual and evidence-based foundation provided in this essay will serve as a roadmap for hypothesis-driven, experimentally validated research on holobionts and their hologenomes, thereby catalyzing the continued fusion of biology's subdisciplines. At a time when symbiotic microbes are recognized as fundamental to all aspects of animal and plant biology, the holobiont and hologenome concepts afford a holistic view of biological complexity that is consistent with the generally reductionist approaches of biology.

Copyright: 2015 Bordenstein, Theis. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Funding: This publication was made possible by National Science Foundation ( ) grants DEB 1046149 and IOS 1456778 to SRB, and IOS 0920505 to KRT. KRT was supported, in part, by the BEACON Center for the Study of Evolution in Action (National Science Foundation Cooperative Agreement DBI 0939454). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The object of this essay is to make the holobiont and hologenome concepts widely known. We clarify and append what they are and are not, explain how they are both consistent with and extend existing theory in ecology and evolutionary biology, and provide a predictive framework for evaluating them. Our goal is to provide the main conceptual foundation for future hypothesis-driven research that unifies perceived divisions among subdisciplines of biology (e.g., zoology, botany, and microbiology) and advances the postmodern synthesis that we are now experiencing [41,42]. We distill this topic with evidence-based reasoning to present the ten principles of holobionts and hologenomes (summarized in Box 1).

To determine if evolutionary changes at the hologenomic level are indeed concordant with evolutionary changes at the nuclear level, there are a handful of critical questions that must be answered across a broad swath of animal and plant clades. How stable is the interspecific covariance, or correlation, between a host and its microbiota and their interacting genes? How consistent is microbial transmission from one holobiont generation to the next? Is genetic disequilibria between host and microbial genes strong enough for evolution to drive covariance and changes in their frequencies over multiple holobiont generations? How much intergenomic epistasis occurs in the hologenome such that one nuclear allele's effect on a trait depends on the state of another microbial allele? Although these inquiries are formidable, they are unquestionably within the realm of population and community genetics approaches.

The debatable and testable issue of the hologenome is whether nuclear genes and microbes are coinherited to a degree that evolution can operate on their interaction. Coinheritance of hologenomic interactions can occur either by vertical transmission via internal (e.g., transovarial) or external (e.g., breast milk) transfer mechanisms or through stable symbioses acquired faithfully from the environment. We discuss these crucial transmission mechanisms further in principle IV.

The geneticist Sewall Wright stated that "selection, whether in mortality, mating or fecundity, applies to the organism as a whole and thus to the effects of the entire gene system rather than to single genes" [94]. In other words, selection operates on phenotypes encoded by the organism's underlying gene system. In this light, the hologenome is the entire gene system of the holobiont, including elements of the nuclear genome, organelles, and microbiome that increase fitness, decrease fitness, or do not affect fitness at all. Within these genomic subunits, mutations are constantly arising at their own finite rates. In the nuclear genome, selection fixes favorable variants and purges the deleterious ones, or "selfish" genes can spread to enhance their own fitness. In the microbiome, selection favors the spread of beneficial microbes involved in nutrition, defense, or reproduction [20], while pathogenic microbes are either purged by holobiont selection or the pathogens deploy adaptations such as reproductive distortions to enhance their selfish transmission to the next generation [95,96]. Moreover, neutral mutations in the nuclear genome can drift to fixation or extinction across generations, as do microbes without any fitness consequences. Thus, nuclear genes with adaptive, deleterious, and neutral mutations that change their frequencies in a holobiont population are generally analogous to beneficial, parasitic, or neutral microbes that also change their frequencies in a holobiont population. How these entities change their frequencies can of course vary with transmission mode, and we address similarities and differences below. Also, classifying microbes at just one end of the symbiotic spectrum pigeonholes the reality that microbial symbioses can be pleiotropic or context-dependent. These varied evolutionary forces can sufficiently explain why animal and plant holobionts harbor species-specific microbial communities that are segregated into their own limited supply of hologenomic variability [31,35].

If hologenomic variation underscores fitness differences, then manipulating the total microbiota will alter host fitness, and therefore germ-free, gnotobiotic, and transbiotic (i.e., populated by an atypical microbiota) hosts will exhibit reduced fitness compared to wild-type and conventionalized hosts. Such predictions need assessment among a broad phylogenetic range of hosts, but ample evidence already exists. For example, in hemipteran insects, germ-free and interspecific gut microbiota cause a decrease in survivorship and delayed development in comparison to control or conventionalized species [97,98], and mice with human gut microbiota have a global immunodeficiency including less T cell proliferation and increased susceptibility to enteric infection [99]. Moreover, interspecific hybridizations can lead to a breakdown in hologenomic interactions within species [100,101].

Every hologenome is a multiple mutant, meaning that there is variation across many individual genomes spanning the nucleus, organelles, and microbiome. Without this variation, there can of course be no evolutionary change in a population of holobionts. Random nucleotide changes are the most obvious source of variation in the hologenome, followed by recombination within and between chromosomes, horizontal gene transfer within and between holobionts, and duplications/losses of gene regions. These changes can occur in any portion of the hologenome, so there is potential for immense genetic diversity across the entire gene network.

Any analysis of holobionts and their hologenomes must also account for the multiple generations that microbes experience within the host's single generation. These differences in generation time are not fatal to the concepts, but they likely affect evolutionary outcomes of the symbiosis. For example, the propensity for symbiosis to drive molecular complexity is now a foundational premise [123], such as in obligate symbionts (with their own generation times) supplementing the missing nutrients in the inadequate diets of thousands of holobiont species spanning cicadas, bedbugs, and aphids [124]. In cicadas, the case is so extreme that genomic and cellular complexity has increased even in the absence of new symbionts via symbiotic heteroplasmy [125]. Notably, even nuclear genomes of mammalian species including humans, nonhuman primates, rodents, and elephants increase in complexity via microbial symbiosis and independent gene transfer events from virus-derived elements [126]. Similarly in Drosophila melanogaster, viral sequences are endogenized adjacent to retrotransposon DNA, and when transcribed, the RNA is altered by the RNA interference (RNAi) machinery and used as part of the immune system to combat lethal viral infections [127].

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