sign in sign up
<<
Home , Cell biology

PERSPECTIVE PERSPECTIVE Evolutionary : Two origins, one objective Michael Lyncha,1, Mark C. Fieldb,2, Holly V. Goodsonc,2, Harmit S. Malikd,e,2, José B. Pereira-Lealf,2, David S. Roosg,2, Aaron P. Turkewitzh,2, and Shelley Sazeri,1 aDepartment of Biology, Indiana University, Bloomington, IN 47405; bDivision of Biological and Drug Discovery, University of Dundee, Dundee DD1 5EH, United ; cDepartment of Chemistry and , University of Notre Dame, Notre Dame, IN 46556; dDivision of Basic Sciences and eHoward Hughes Medical Institute, Fred Hutchinson Research Center, Seattle, WA 98195; fInstituto Gulbenkian de Ciência, P-2781-901 Oeiras, Portugal; gDepartment of Biology, University of Pennsylvania, Philadelphia, PA 19143; hDepartment of Molecular and Cell Biology, University of Chicago, Chicago, IL 60637; and iVerna and Marrs McLean Department of Biochemistry and , Baylor College of , Houston, TX 77030

Edited by W. Ford Doolittle, Dalhousie University, Halifax, NS, Canada, and approved October 20, 2014 (received for review September 3, 2014)

All aspects of biological diversification ultimately trace to evolutionary modifications at the cellular level. This central role of cells frames the basic questions as to how cells work and how cells come to be the way they are. Although these two lines of inquiry lie respectively within the traditional provenance of cell biology and , a comprehensive synthesis of evolutionary and cell-biological thinking is lacking. We define evolutionary cell biology as the fusion of these two eponymous fields with the theoretical and quantitative branches of biochemistry, , and genetics. The key goals are to develop a mechanistic understanding of general evolutionary processes, while specifically infusing cell biology with an evolutionary perspective. The full development of this interdisciplinary field has the potential to solve numerous problems in diverse areas of biology, including the degree to which selection, effectively neutral processes, historical contingencies, and/or constraints at the chemical and biophysical levels dictate patterns of variation for intracellular features. These problems can now be examined at both the within- and among-species levels, with single-cell methodologies even allowing quantification of variation within . Some results from this emerging field have already had a substantial impact on cell biology, and future findings will significantly influence applications in agriculture, medicine, environmental science, and .

evolutionary cell biology | cell biology | adaptive | random | cellular evolution

The origin of cells constituted one of ’s levels, much of today’s study of evolution is motivate and illustrate the potential for this most important early evolutionary transi- only moderately concerned with cellular fea- new field. tions, simultaneously enabling replicating en- tures, perhaps due to lack of appreciation for Why Are Cells the Way They Are, and tities to corral the fruits of their catalytic their wide variation among taxa. However, Why Aren’t They Perfect? labor and providing a unit of inheritance nec- a full mechanistic understanding of evolu- essary for further evolutionary refinement tionary processes will never be achieved with- Although it is easy to marvel about the re- and diversification. The centrality of cellular out an elucidation of how cellular features fined features of cells and their robustness to features to all aspects of biology motivates the become established and modified. perturbations (1), the field of bioengineering focus of cell biology on the biophysical/bio- The time is ripe for bridging the gap imagines and even implements more efficient chemical aspects of a broad swath of traits between the historically disconnected fields cellular mechanisms in extant . that include gene expression, , in- of cell biology and evolutionary biology and What, then, limits the levels of molecular/ – tracellular transport and communication, cell integrating them with the principles of cellular refinements that have been ach- cell interactions, locomotion, and growth. No biophysics and biochemistry into a formal ieved by ? one questions the rich contributions that have field of evolutionary cell biology. Recent resulted from this focus on how cells work. To What Extent Is Cell Biology Beholden advances in cell-biological analysis and the However, with an emphasis on maximizing to Historical Contingency? We have learned acquisition of ’omic-scale datasets have experimental consistency in a few well-char- an enormous amount about the genetic broadened the opportunities for research acterized model systems, cell have mechanisms of evolution since Darwin, and on nonstandard model organisms, thereby generally eschewed the variation that moti- it remains true that evolution is an opportu- facilitating the incorporation of phyloge- vates most questions in evolutionary biology. nistic process of “descent with modification,” Because all evolutionary change ultimately netic diversity into cell-level studies. Our requires modifications at the cellular level, vision for this synthesis is motivated by the growing realization in both communi- Author contributions: M.L., M.C.F., H.V.G., H.S.M., J.B.P.-L., D.S.R., questioning and understanding how cellular A.P.T., and S.S. wrote the paper. ties that an intellectual merger will yield features arise and diversify should be a central The authors declare no conflict of interest. dramatic increases in our understanding research venue in evolutionary biology. How- This article is a PNAS Direct Submission. of cell-biological , functions, and ever, if there is one glaring gap in this field, it 1To whom correspondence may be addressed. Email: milynch@ is the absence of widespread cell-biological processes, as well as insights into the cellu- indiana.edu or [email protected].

thinking. Despite the surge of interest at lar basis for evolutionary change. Although 2M.C.F., H.V.G., H.S.M., J.B.P.-L., D.S.R., and A.P.T. contributed the molecular, genomic, and developmental not an exhaustive list, the following questions equally to this work.

www.pnas.org/cgi/doi/10.1073/pnas.1415861111 PNAS Early Edition | 1of5 Downloaded by guest on September 30, 2021 working with the resources made available order structures such as dimers, tetramers, etc. pathways (19–23), transport (24), in previous generations. Once established, Remarkably, however, unlike the strong, gen- nuclear organization (25), and useful features cannot be easily dismantled eraltrendtowarddramaticincreasesingene production (26, 27). These kinds of obser- and reassembled de novo unless there is an structural complexity from to vations imply that there are often numerous intermediate period of redundancy. unicellular to multicellular species degrees of freedom for reorganizing the un- One remarkable example of how history (7), higher-order structural complexity of derlying determinants of otherwise constant continues to influence today’s cell biology is does not noticeably scale with cellular processes. the near universal use of ATP synthase as organismal complexity across the Tree of a mechanism for generation (2). Em- Life (8). Comparative biochemical and How Much of Cellular Complexity Is the bedded in the surface membranes of protein-structural analysis within a phylo- Result of ? A commonly held and organellar membranes of eukaryotes, this genetic framework has great potential to but incorrect stance is that essentially all of complex uses the potential address many outstanding questions in this evolution is a simple consequence of natural energy of a proton gradient to generate a ro- area, including whether variation in the selection. Leaving no room for doubt on the tational force that converts ADP to ATP, multimeric states of proteins is a simple process, this narrow view leaves the impres- much like a turbine converts the potential consequence of stochastic of ad- sion that the only unknowns in evolutionary energy of a water gradient into electricity. hesive interface residues, with minimal biology are the identities of the selective However, the proton gradient does not come effects on catalytic efficiency. agents operating on specific traits. However, for free: cells first use energy derived from Similar questions arise about the biophysical population-genetic models make clear that metabolism to pump protons out of mem- properties of supermolecular structures, such the power of natural selection to promote brane-bound compartments, creating the as , actin filaments, and the beneficial mutations and to remove deleteri- gradient necessary for reentry through ATP endomembrane systems of eukaryotic cells ous mutations is strongly influenced by other synthase. Even assuming that ATP pro- (9). The self-assembly of bilayers factors. Most notable among these factors is duction is an essential requirement for emerges spontaneously from the biophysical random genetic drift, which imposes noise in the origin of life, it is by no means clear properties of amphiphilic , and re- the evolutionary process owing to the finite that the path chosen for ADP-to-ATP cent origin-of-life research suggests that some numbers of individuals and conversion is the only possibility. of the key first steps in the origin of life, such architecture. Such stochasticity leads to the Rather, the universal reliance of all of life as the assembly and division of vesicles, are drift-barrier hypothesis for the evolvable lim- on this mechanism of energy conversion may inevitable consequences of the behavior of its to molecular refinement (28, 29), which be a historical relic of the exploitable energy organic molecules in water (10, 11). postulates that the degree to which natural source present at the time of life’s foundation: Finally, general biophysical phenomena selection can refine any adaptation is defined e.g., a precellular period in which energy ac- are undoubtedly involved in the patterning of by the genetic effective population size. One quisition derived from a natural proton gra- phenotypes at the whole-cell level. For ex- of the most dramatic examples of this prin- dient between overlying low-pH marine waters ample, constraints on surface:volume scaling ciple is the inverse relationship between levels and the alkaline interiors of vent mounds (3, may have been involved in the establishment of replication fidelity and the effective pop- 4). Despite the central significance of ATP of internal membranes and their above-noted ulation sizes of species across the Tree of Life synthase to across the Tree of associations with bioenergetics (12). Such (30). Reduced effective population sizes also Life and the invariance of the basic mechanism constraints may also have played a central lead to the establishment of weakly harmful of ATP regeneration, many examples are role in the evolution of cell size and features embellishments such as introns and mobile- known in which the of the complex of the (13). The emergence element insertions (7). Thus, rather than has been modified with respect to the num- of the nuclear envelope may have, in turn, genome complexity being driven by natural bers and types of subunits (2, 5, 6). had secondary evolutionary consequences, selection, many aspects of the former actually such as the establishment of a permissive en- arise as a consequence of inefficient selection. How Is Cell Biology Constrained by the vironment for intron proliferation (7), which Indeed, many pathways to greater com- Laws of Physics and Chemistry? Although requires efficient pretranslational splicing plexity do not confer a selective fitness ad- cataloging and explaining are cen- of transcripts. vantage at all. For example, due to pervasive tral themes of evolutionary biology, deciphering Although the preceding observations sug- duplication of entire genes (7) and their the roles by which biophysical/biochemical gest that the emergence and diversification of regulatory regions (31) and the promiscuity barriers channel cellular characteristics into numerous cellular features may be predict- of many proteins (32), genes commonly ac- a limited range of alternatives is equally able on biophysical grounds alone, the im- quire multiple modular functions. Sub- important. Like the near-universal genetic position of constraints on a complex trait sequent duplication of such genes can then code, the laws of physics endow cells with need not preclude substantial opportunities lead to a situation in which each copy loses specific properties, but, unlike the nucleotide for modifying the underlying components, as a complementary subfunction, channeling sequences of genes, these laws are immuta- previously discussed with respect to ATP both down independent evolutionary paths ble and have potential impacts at all levels of synthase. For example, although there are (33). Such dynamics may be responsible for biological organization. common organizational principles in diverse the numerous cases of rewiring of regula- Examples of relevant organizing principles regulatory, signal-transduction, and meta- tory and metabolic networks noted in the at the molecular scale include the role of the bolic pathways, dramatic cases of rewiring previous section (34, 35). In addition, the hydrophobic effect in protein folding and have been revealed with the expansion of effectively neutral acquisition of a protein– assembly and constraints imposed by in- molecular and cell biological investigations to protein-binding interaction can facilitate tracellular molecular crowding. For example, multiple species. Such examples include the subsequent accumulation of mutational rather than operating as monomers, the ma- aspects of mating-type specification (14, 15), alterations of interface residues that would jority of proteins self-assemble into higher- (16), (17, 18), biosynthetic be harmful if exposed, thereby rendering

2of5 | www.pnas.org/cgi/doi/10.1073/pnas.1415861111 Lynch et al. Downloaded by guest on September 30, 2021 what was previously a monomeric structure variation that has a genetic basis. Estimation complexes called adaptins. Although it had PERSPECTIVE permanently and irreversibly heteromeric (8, of these key parameters is now within reach been accepted for over a decade that there are 36–39). Finally, although it has long been as- as new technologies allow assays of single only four adaptin complexes in eukaryotes, sumed that selection virtually always accepts cells in a high-throughput manner. Applica- comparative suggested the pres- only mutations with immediate positive effects tions of these methods to genetically uniform ence of a fifth highly divergent adaptin-like on fitness, it is now known that, in sufficiently reveal substantial cell-to-cell complex across eukaryotes (53). Subsequent large populations, trait modifications in- variation in gene-specific numbers of tran- characterization of the protein in human cells volving mutations with individually deleteri- scripts and proteins in all domains of life identified its cellular location and , ous effects can become established in large (43–45), and such variation (intrinsic cellular thereby fundamentally altering our basic populations when the small subset of mal- noise) seems to be a natural outcome of understanding of vesicle-transport systems adapted individuals maintained by recurrent biophysical features of interactions between and the likely order of evolutionary events acquire complementary secondary transcription factors and their binding sites, leading to their diversification. An even more mutations that restore or even enhance fitness which can be quantified in mechanistic recent phylogenetic analysis suggests the ex- (40, 41). terms (46, 47). These kinds of observations, istence of a sixth form of adaptor complex One goal of evolutionary cell biology which can be extended to other intracellular (54), raising the possibility that still more should be to determine whether these general traits (48), are essential to understanding the remain to be discovered, perhaps with some principles involving effectively neutral paths limits to the evolvability of cellular features. complexes being restricted to a subset of taxa. of molecular evolution extend to even higher- This is because environmental variance (in- A second striking example of the power of order biological features, such as intracellular tracellular noise) reduces the ability of a comparative analysis to inform our basic architecture (37). Is natural selection a suffi- population to respond to selection by over- understanding of cell biology involves the cient or even a necessary explanation for the shadowing the heritable genetic component discovery of an evolutionary relationship evolution of the complex features of the ri- of variation (49). between what were considered two very dif- bosome, the , the nuclear-pore Although conceptually straightforward, ferent kinds of membrane-deformation pro- complex, and the ? Or is a resolving the degree to which variation (and teins. Cargo transport in eukaryotic cells march toward increased, and potentially covariation) of phenotypes in populations of involves the use of diverse pathways initiating irreversible, cellular complexity an inevitable cells is a consequence of genetic vs. envi- with membrane-coated vesicles supported by outcomeofmutationpressureandthein- ronmental causes will require large-scale ex- clathrin, and the cage forming proteins of efficiencies of selection processes in finite perimental designs including genetically cytoplasmic coat protein complexes I and II populations? variable isolates. When applied in this way, (COPI and COPII). Although these proteins The points raised above are not meant to single-cell phenotyping down to the level of are lacking in amino acid sequence similarity, suggest that structures as complex as ribo- individual molecules has the potential to comparative structural analysis suggests a somesorATPsynthasearemaladaptive. revolutionize the field of quantitative ge- common molecular architecture that is also Certainly, today’s cells cannot survive with- netics by elucidating the precise sources of related to the membrane-curving proteins out such molecular machines. However, the variation underlying the expression of involved in both the nuclear-pore complex existence of complex cellular features need higher-order cellular features. Notably, the (NPC) (55) and the adaptins discussed above. not imply that each of the myriad of changes statistical framework of quantitative ge- The structural and functional insights that sculpted such structures over evolution- netics is also fully equipped to address the emerging from these observations guided ary time was adaptive at the time of estab- evolutionary consequences of transient the development of a mechanistic un- lishment. The determination of whether it is epigenetic effects (49), whose influences derstanding of the NPC (56) and yielded even feasible for a cellular innovation to have aredissipatedovertimewithvariouslevels a novel evolutionary proposal—the “pro- been promoted by purely adaptive pro- of reinforcement (e.g., refs. 50–52). tocoatomer” hypothesis, which postulates cesses cannot be made in the absence of that many vesicle-coating complexes and Where Do Cellular Innovations Map onto information about the population-ge- the NPC arose by descent with modifica- netic environment: i.e., the magnitudes of the Tree of Life? tion (55). Among other things, this con- the power of mutation, recombination, A first step in nearly all studies in evolu- cept has provided a potential explanation and random genetic drift. All three fea- tionary biology is the elucidation of phy- for how the diverse plans of eukaryotic tures vary by orders of magnitude across logenetic patterns of variation. Although cells could have arisen from a simpler theTreeofLifeandcanonlyroughlybe a purely historical perspective cannot re- -like ancestor. inferred for ancestral species. Uncertainty veal the mechanisms by which evolution In a third example, an integration of mo- in this area is a major challenge for evo- proceeds, it does clarify what needs to be lecular and morphological phylogenetic lutionary cell biology (30, 42). explained. Traditional cell biology is largely analysis has led to the identification of novel devoid of comprehensive comparative ana- components of and cilia, as well as How Do Cellular Innovations Arise? lyses, but recent studies demonstrate the to evolutionary hypotheses for how their For practical reasons, cell biology has his- power of such approaches, as illustrated by coordinated biogenesis and functions in dif- torically focused on the average features of the following three examples. ferent cellular contexts have been achieved the members of large populations of geneti- Thefirstexampleaddressestheevolu- through duplication and divergence of an cally uniform cells. However, natural selec- tionary origins of the network of ancestral gene set (57, 58). tion does not operate directly on population and underlying molecular features by which This small set of examples illustrates means but on variation among individuals. membrane trafficking emerged in eukaryotes. the considerable potential for more elab- Moreover, the evolutionary response to The sorting of proteins and among the orate comparative analyses to elucidate selection on a trait is not a simple matter of intracellular compartments of eukaryotic cells the evolutionary foundations of the most variation, but a function of the fraction of is mediated in part by a family of protein basic eukaryotic cellular features. Of course,

Lynch et al. PNAS Early Edition | 3of5 Downloaded by guest on September 30, 2021 ascertainment of where cell-biological in- coupled to detailed studies of individual gene and where it might lead, consider that whole- novations map onto the Tree of Life and products in diverse taxa. To this end, we genome sequencing was barely a dream 25 y inference of phylogenetic points of gain envision the need for a new grand challenge ago but, in the past decade, has revolution- and loss of various modifications will in biology, such as the proposed Atlas of the ized virtually every aspect of biology, vastly require a substantial increase in taxonomic Biology of Cells (www.nsf.gov/publications/ increasing our understanding of human- sampling of cellular diversity. Of the esti- pub_summ.jsp?ods_key=bio12009). The fun- genetic disorders, methods for disease con- mated 5–100 million extant species, only damental idea here is to develop a database trol, energy production, and ∼1.5 million have been described at even for cellular/subcellular features for a judi- function. Such advances continue to inspire a rudimentary level, and most of these taxa ciously chosen, phylogenetically broad set of the development of new ’omics technologies are heavily biased toward , , organisms, with the goal of sampling the with enormous increases in accuracy and fungi, and microbes with direct human functional diversity of metabolic and cellular efficiency, as well as the emergence of novel impact (59) (Fig. 1). Future studies of bio- morphological traits in the fullest possible computational technologies for storage, in- diversity are likely to continue to extend to sense. To be maximally productive, such an tegration, and analysis that facilitate the the discovery of novel phyla for quite some enterprise will require the further develop- rapid transformation of data into knowledge. – time (e.g., refs. 60 62). These issues, to- ment of automated, generalizable, and How Can Effective Implementation of gether with the fact that typically about high-throughput cell-biological methods. Lessons from Evolutionary Cell Biology a third of predicted protein-coding genes Significantsupportforappropriatephy- Be Ensured? per sequenced genome are undefined and/ logenetic sampling, development of reli- Cell biology textbooks traditionally focus or restricted to narrow taxonomic group- able culture methods, and standardized on structures and pathways perceived to ings, make clear that we are still missing measurement methodology will also be be common to all cells, only occasionally immense swaths of information on cellular necessary. Most importantly, the latter will “ ” addressing specializations in individual phy- diversity. This missing phylogeny is likely require the establishment of not only con- logenetic lineages, and even more rarely of high value to applied research efforts trolled vocabularies and ontologies to provide mentioning their modes of diversification. In in medicine, agriculture, and environ- a conceptual framework for data comparison, effect, we have built up a sort of canonical mental science. but also quantitative metrics for defining, molecular and cell biology based on a few Unfortunately, parts lists inferred from comparing, and predicting cell-biological serendipitously selected model organisms. genome information alone can take us only structures and processes. How things work in Escherichia coli, Saccha- so far. Although results from transcriptomics, The payoffs of such an organized research romyces cerevisiae, Drosophila melanogaster, metabolomics, etc. can provide additional program are likely to be substantial. As an and mouse cells is all too often viewed as information, such work must ultimately be analogy to where evolutionary cell biology is the “normal” mode of biology, with dif- ferences observed in other organisms of- ten being viewed as little more than amusing oddities. Imagine what today’s biology might look like if our models had been Nanoarchaeum (archaebacterium), Par- amecium (ciliate), Ceratium (dinoflagellate), and Pinus (gymnosperm). The view that intracellular structures are essentially invariant in diverse organisms engenders the false impression that an evo- lutionary has little to gain by pur- suing studies at the cellular level. Moreover, the few statements about evolution that can be found in cell-biology textbooks and journal articles frequently speculate on the adaptive significance of cellular fea- tures, oversimplifying and obscuring our understanding of evolutionary mecha- nisms (42, 63). This outmoded view of evo- lutionary processes still gives rise to major misunderstandings, with substantial implica- tions (64). Fig. 1. Taxonomic distribution of research articles and sequenced genomes. Modern identifies five major In summary, we have attempted to high- eukaryotic supergroups: the Excavates (turquoise), Chromalveolates (orange), Archaeplastida (green), Amoebozoa light why bridging the conceptual gap be- (purple), and Opisthokonts (red). Although the total number of species on earth remains unknown, it is clear that there are far more unicellular eukaryotes than the combined total of all animals (Metazoa, an Opisthokont lineage), fungi tween cell biology and evolutionary biology is (also Opisthokonts), and plants (Archaeplastida). However, research activity displays considerable taxonomic bias. As likely to enrich our understanding of virtually of January 2014, the National Center for Information taxonomy browser (www.ncbi.nlm.nih.gov/ all biological processes. For example, al- Taxonomy/Browser/wwwtax.cgi) lists 338 Archaeal genomes (dark gray), 20,709 Eubacteria (light gray), 769 Metazoa, though the natural spatial delimitation of cell 1,201 Fungi, 251 green plants/, and 336 genomes from all other eukaryotic taxa (13% of eukaryotic genomes). The taxonomic distribution of PubMed citations is as follows: , 19,000; Eubacteria, 397,000; Metazoa, biology resides at the , an 576,000; Fungi, 135,000; green plants/algae, 168,000; and all other eukaryotes combined, 97,000 (<9% of pub- understanding of the evolutionary roots of lications on Eukaryotes). variouscellularfeaturesisofcentralrelevance

4of5 | www.pnas.org/cgi/doi/10.1073/pnas.1415861111 Lynch et al. Downloaded by guest on September 30, 2021 to evolutionary developmental biologists removal of real and perceived conceptual National Science Foundation-sponsored Workshop on PERSPECTIVE concerned with the origin of cell types (65). Evolutionary Cell Biology (Grant MCB-1228570), and we and communication barriers (including acknowledge the many insightful discussions among the Evolutionary cell biology has a particularly those engendered by the use of specialized participants (for details, see www.nsf.gov/publications/ high potential for informing a variety of vocabularies) and the design and imple- pub_summ.jsp?ods_key=bio12009). We are grateful practical matters with ecological, economic, mentation of cross-disciplinary educational for support from National Science Foundation Grants and health benefits. Such applications include IOS-1051962 (to S.S.), MCB-1050161 (to M.L.), MCB- initiatives are central keys to building an 1051985 (to A.P.T.), and MCB-1244593 (to H.V.G.), the facilitation of drug development and the interactive of essen- National Institutes of Health Grants R01-GM036827 elucidation of the mechanisms of drug sen- (to M.L.), R01-105783 (to A.P.T.), R01-GM74108 (to tial for igniting an effective field of evolu- sitivity and resistance, and of the identifica- H.S.M.), and R01-AI49301 (to D.S.R.), US Army Re- tionary cell biology. search Office Grant W911NF-09-1-0444 (to M.L.), and tion of the mechanisms of nutrient fluxes Fundação para a Ciência e Tecnologia Grant PTDC/EBB- through the environment and their de- ACKNOWLEDGMENTS. We thank W. Ford Doolittle for BIO/119006/2010 (to J.B.P.-L.). H.S.M. is an Investigator pendence on species-specific features. The helpful comments. This paper was, in part, inspired by the of the Howard Hughes Medical Institute.

1 Wagner A (2007) Robustness and Evolvability in Living Systems 23 Oria-Hernández J, Riveros-Rosas H, Ramírez-Sílva L (2006) 45 Taniguchi Y, et al. (2010) Quantifying E. coli proteome and (Princeton Univ Press, Princeton). Dichotomic of the pyruvate kinase family: K+ transcriptome with single- sensitivity in single cells. Science 2 Walker JE (2013) The ATP synthase: The understood, the uncertain -dependent and -independent . J Biol Chem 281(41): 329(5991):533–538. and the unknown. Biochem Soc Trans 41(1):1–16. 30717–30724. 46 Shahrezaei V, Swain PS (2008) Analytical distributions for 3 Martin W, Baross J, Kelley D, Russell MJ (2008) Hydrothermal vents 24 Raposo G, Marks MS (2002) The dark side of -related stochastic gene expression. Proc Natl Acad Sci USA 105(45): and the origin of life. Nat Rev Microbiol 6(11):805–814. organelles: Specialization of the endocytic pathway for 17256–17261. 4 Lane N, Allen JF, Martin W (2010) How did LUCA make a living? biogenesis. Traffic 3(4):237–248. 47 Thattai M, van Oudenaarden A (2001) Intrinsic noise in gene Chemiosmosis in the origin of life. BioEssays 32(4):271–280. 25 Devos DP, Gräf R, Field MC (2014) Evolution of the nucleus. Curr regulatory networks. Proc Natl Acad Sci USA 98(15):8614–8619. 5 Balabaskaran Nina P, et al. (2010) Highly divergent mitochondrial Opin Cell Biol 28:8–15. 48 Farhadifar R, Needleman D (2014) Automated segmentation of ATP synthase complexes in Tetrahymena thermophila. PLoS Biol 8(7): 26 Lavoie H, et al. (2010) Evolutionary tinkering with conserved the first mitotic spindle in differential interference contrast microcopy e1000418. components of a transcriptional regulatory network. PLoS Biol 8(3): images of C. elegans embryos. Methods Mol Biol 1136:41–45. 6 Lapaille M, et al. (2010) Atypical subunit composition of the e1000329. 49 Lynch M, Walsh JB (1998) Genetics and Analysis of Quantitative chlorophycean mitochondrial F1FO-ATP synthase and role of Asa7 27 Tanay A, Regev A, Shamir R (2005) Conservation and evolvability Traits (Sinauer Associates, Sunderland, MA). protein in stability and oligomycin resistance of the . Mol Biol in regulatory networks: The evolution of ribosomal regulation in 50 Azimzadeh J, Marshall WF (2010) Building the . Curr Biol – – Evol 27(7):1630–1644. . Proc Natl Acad Sci USA 102(20):7203 7208. 20(18):R816 R825. 7 Lynch M (2007) The Origins of Genome Architecture (Sinauer 28 Lynch M (2011) The lower bound to the evolution of mutation 51 Colby DW, Prusiner SB (2011) Prions. Cold Spring Harb Perspect – Associates, Sunderland, MA). rates. Genome Biol Evol 3:1107 1118. Biol 3(1):a006833. 8 Lynch M (2013) Evolutionary diversification of the multimeric 29 Lynch M (2012) Evolutionary layering and the limits to cellular 52 Shimi T, Butin-Israeli V, Adam SA, Goldman RD (2010) Nuclear – states of proteins. Proc Natl Acad Sci USA 110(30):E2821–E2828. perfection. Proc Natl Acad Sci USA 109(46):18851 18856. lamins in cell regulation and disease. Cold Spring Harb Symp Quant – 9 Karsenti E (2008) Self-organization in cell biology: A brief history. 30 Sung W, Ackerman MS, Miller SF, Doak TG, Lynch M (2012) Drift- Biol 75:525 531. barrier hypothesis and mutation-rate evolution. Proc Natl Acad Sci 53 Hirst J, et al. (2011) The fifth adaptor protein complex. PLoS Biol Nat Rev Mol Cell Biol 9(3):255–262. – 10 Budin I, Szostak JW (2011) Physical effects underlying the USA 109(45):18488 18492. 9(10):e1001170. 31 Force A, et al. (2005) The origin of subfunctions and modular 54 Hirst J, et al. (2014) Characterization of TSET, an ancient and transition from primitive to modern cell membranes. Proc Natl Acad gene regulation. Genetics 170(1):433–446. widespread membrane trafficking complex. eLife 3:e02866. Sci USA 108(13):5249–5254. 32 Tokuriki N, Tawfik DS (2009) Protein dynamism and evolvability. 55 Devos D, et al. (2004) Components of coated vesicles and 11 Chen IA (2006) GE Prize-winning essay: The emergence of cells Science 324(5924):203–207. nuclear pore complexes share a common molecular architecture. during the origin of life. Science 314(5805):1558–1559. 33 Force A, et al. (1999) Preservation of duplicate genes by PLoS Biol 2(12):e380. 12 Lane N, Martin W (2010) The energetics of genome complexity. complementary, degenerative mutations. Genetics 151(4): 56 Devos D, et al. (2006) Simple fold composition and modular 467(7318):929–934. 1531–1545. architecture of the nuclear pore complex. Proc Natl Acad Sci USA 13 Cavalier-Smith T (1978) Nuclear volume control by nucleoskeletal 34 Tuch BB, Li H, Johnson AD (2008) Evolution of eukaryotic 103(7):2172–2177. DNA, selection for cell volume and rate, and the solution transcription circuits. Science 319(5871):1797–1799. 57 Carvalho-Santos Z, Azimzadeh J, Pereira-Leal JB, Bettencourt- of the DNA C-value paradox. J Cell Sci 34:247–278. 35 Lynch M (2007) The evolution of genetic networks by non- Dias M (2011) Evolution: Tracing the origins of centrioles, cilia, and 14 Baker CR, Tuch BB, Johnson AD (2011) Extensive DNA-binding adaptive processes. Nat Rev Genet 8(10):803–813. flagella. J Cell Biol 194(2):165–175. specificity divergence of a conserved transcription regulator. Proc 36 Stoltzfus A (1999) On the possibility of constructive neutral 58 Carvalho-Santos Z, et al. (2010) Stepwise evolution of the Natl Acad Sci USA 108(18):7493–7498. evolution. J Mol Evol 49(2):169–181. centriole-assembly pathway. J Cell Sci 123(Pt 9):1414–1426. 15 Singh DP, et al. (2014) Genome-defence small exapted for 37 Lukes J, Archibald JM, Keeling PJ, Doolittle WF, Gray MW (2011) 59 Mora C, Tittensor DP, Adl S, Simpson AG, Worm B (2011) How – epigenetic mating-type inheritance. Nature 509(7501):447 452. How a neutral evolutionary ratchet can build cellular complexity. many species are there on Earth and in the ocean? PLoS Biol 9(8): 16 Kohl KP, Sekelsky J (2013) Meiotic and mitotic recombination in IUBMB Life 63(7):528–537. e1001127. – meiosis. Genetics 194(2):327 334. 38 Finnigan GC, Hanson-Smith V, Stevens TH, Thornton JW (2012) 60 Kim E, et al. (2011) Newly identified and diverse -bearing 17 Cross FR, Buchler NE, Skotheim JM (2011) Evolution of networks Evolution of increased complexity in a molecular machine. Nature branch on the eukaryotic tree of life. Proc Natl Acad Sci USA 108(4): and sequences in eukaryotic cell cycle control. Philos Trans R Soc 481(7381):360–364. 1496–1500. – Lond B Biol Sci 366(1584):3532 3544. 39 Lynch M (2012) The evolution of multimeric protein 61 Keeling PJ, et al. (2014) The Marine Microbial 18 Harashima H, Dissmeyer N, Schnittger A (2013) Cell cycle control assemblages. Mol Biol Evol 29(5):1353–1366. Transcriptome Sequencing Project (MMETSP): Illuminating the – across the eukaryotic kingdom. Cell Biol 23(7):345 356. 40 Lynch M, Abegg A (2010) The rate of establishment of complex functional diversity of eukaryotic life in the oceans through 19 Koonin EV, Mushegian AR, Bork P (1996) Non-orthologous gene . Mol Biol Evol 27(6):1404–1414. transcriptome sequencing. PLoS Biol 12(6):e1001889. displacement. Trends Genet 12(9):334–336. 41 Weissman DB, Feldman MW, Fisher DS (2010) The rate of fitness- 62 Karsenti E, et al.; Tara Oceans Consortium (2011) A holistic 20 Omelchenko MV, Galperin MY, Wolf YI, Koonin EV (2010) Non- valley crossing in sexual populations. Genetics 186(4):1389–1410. approach to marine eco-. PLoS Biol 9(10):e1001177. homologous isofunctional enzymes: A systematic analysis of 42 Lynch M (2007) The frailty of adaptive hypotheses for the origins 63 Gould SJ, Lewontin RC (1979) The spandrels of San Marco and alternative solutions in enzyme evolution. Biol Direct 5:31. of organismal complexity. Proc Natl Acad Sci USA 104(Suppl 1): the Panglossian paradigm: a critique of the adaptationist programme. 21 Allen AE, et al. (2012) Evolution and functional diversification of 8597–8604. Proc R Soc Lond B Biol Sci 205(1161):581–598. fructose bisphosphate aldolase genes in photosynthetic marine 43 Newman JR, et al. (2006) Single-cell proteomic analysis of 64 Graur D, et al. (2013) On the of television sets: diatoms. Mol Biol Evol 29(1):367–379. S. cerevisiae reveals the architecture of biological noise. Nature “Function” in the human genome according to the evolution-free 22 Liapounova NA, et al. (2006) Reconstructing the mosaic 441(7095):840–846. gospel of ENCODE. Genome Biol Evol 5(3):578–590. glycolytic pathway of the anaerobic eukaryote Monocercomonoides. 44 Schwanhäusser B, et al. (2011) Global quantification of 65 Arendt D (2008) The evolution of cell types in animals: emerging Eukaryot Cell 5(12):2138–2146. mammalian gene expression control. Nature 473(7347):337–342. principles from molecular studies. Nat Rev Genet 9(11):868–882.

Lynch et al. PNAS Early Edition | 5of5 Downloaded by guest on September 30, 2021