Proc. Natl. Acad. Sci. USA Vol. 93, pp. 14229–14232, December 1996 Colloquium Paper This paper was presented at a colloquium entitled ‘‘Symmetries Throughout the Sciences,’’ organized by Ernest M. Henley, held May 11–12, 1996, at the National Academy of Sciences in Irvine, CA. Symmetries throughout organic evolution ANTONIO GARCI´A-BELLIDO Centro de Biologı´a Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientı´ficas, Universidad Auto´noma de Madrid, Cantoblanco, 28049-Madrid, Spain ABSTRACT The biological realm has inherited symme- tions are similarly dextrorotatory. We now know that the tries from the physicochemical realm, but with the increasing prevalence of D-isomers is due to the asymmetry of the active complexity at higher phenomenological levels of life, some catalytic sites of the enzymes that recognize saccharides for inherited symmetries are broken while novel symmetries both their anabolism and catabolism. The reason for the appear. These symmetries are of two types, structural and prevalence of saccharide D-isomers and their derivatives (tar- operational. Biological novelties result from breaking opera- taric acid is one) may be that the corresponding metabolic tional symmetries. They are followed by acquisition of regu- enzymes are encoded by genes all evolutionarily descended larity and stability, in a recurrent process throughout com- from one original prototype. The same may hold for the plexity levels. prevalence of L-phospholipids that are metabolized by many different types of phospholipases. From the predominance of The concept of symmetry implies conservation of shape upon D- over L-isomers of saccharides and of L-phospholipids, we rotation or of isomorphic transformation in interactions, re- learn two important lessons about biological evolution. Ones taining one or several parameters invariant in the transforma- in that molecular recognition provides a profound inertia to tion. These attributes correspond both to topological and evolutionary innovation because it demands conservation of operational properties in the stability and evolution of func- forms of proteins and hence of the encoding genes. The other tional structures. In biology the counterpart of these notions is that the contingent origins of saccharide metabolism am- has synchronic (e.g., anatomic or physiologic) as well as plified asymmetries in the abundance of equally probable, diachronic (e.g., developmental and evolutionary) connota- energetically equivalent, isomers. tions. In dealing with these two connotations, I will try to The same lessons can be draw from the prevalence of L- over distinguish between topological and operational symmetries, D-amino acid isomers in biomolecules. Enzymes involved in being aware that the use of these terms in the context of amino acid metabolism may have derived from a common biology extends beyond the more precise meaning in the prototype that prevailed in the competition between isomeric context of physics. Whereas the notion of topological symme- forms in the primordial organic soup. The consequences were try in biological forms is well documented, that of operational everlasting, since the form of all the proteins whose function symmetry has been, to my knowledge, hardly considered. As in requires amino acid recognition must be complementary to the physics, also in biology, devolving interactions generate breaks form of the L-isomers. Moreover, the helical rotation of long of symmetry. Herein I will discuss briefly a few instances of helical polypeptide chains is derived from the tilt of peptide symmetries and its breaks in biology that have played a central bonds between L-amino acid residues. And that configuration role in organic evolution. is, in turn, basic to many of the elastic properties of proteins Biology deals with forms and their transformations: molec- in structural and functional roles. ular, cellular, histological, organismal, and ecological. Its Similarly, the two polynucleotide chains in the double- structures are grounded in the physical realm and its energetic helical DNA molecule have a clockwise axial rotation based on transactions in the chemical one. In this ascent throughout the tilt imposed by the staggering of successive nucleotides. In complexity levels, we cannot discriminate between historical this case, the degrees of freedom of this rotation are greater contingency and strict causal determination, although the than those available to polypeptides chains because the DNA former seems to play a major role with increasing complexity. molecule can have an opposite rotational torque under phys- Organic evolution devolves from combinatorial propositions iological conditions. The primary helicity of the DNA is a that happened to succeed, i.e., were stable and stayed around consequence of its mode of generation and causes its structural for us to observe and categorize. stability that carries on its higher-order organization allowing for protein recognition sites, complex replication and tran- Structural or Topological Symmetries scription mechanisms, and tertiary folding into chromosomes for cytokinesis. The linear sequence of nucleotide residues in The formation of anisodiametric molecules by the bonding of DNA double strands is on the other hand, constrained by isodiametric atoms is the first symmetry break that gives rise purine–pyrimidine base complementarity required for the to fundamentally asymmetric biological structures. stability of the double helix. But beyond this, the order of The first example of a biologically caused break of molecular nucleotides can in principle be arbitrary. The same freedom of symmetry paradigmatic for many biological structures was nucleotide sequence holds for single-stranded RNA molecules. discovered by Pasteur. Whereas molecules of tartaric acid, can However, in RNA molecules, a new symmetry appears in exist as two optically active, dextro (D) or levo (L) rotatory palindromic nucleotide sequences, at which the single RNA isomers, yeast cells can only metabolize the D-isomers. It so strand folds back on itself by nucleotide base complementarity; happens that all saccharides in biological structures and reac- pins and four-leafed configurations due to palindromic con- figurations are responsible for the stability and molecular The publication costs of this article were defrayed in part by page charge recognition features of RNA molecules. They correspond to payment. This article must therefore be hereby marked ‘‘advertisement’’ in emerging symmetries with profound biological implications. It accordance with 18 U.S.C. §1734 solely to indicate this fact. is precisely these secondary interactions of biological macro- 14229 Downloaded by guest on October 3, 2021 14230 Colloquium Paper: Garcı´a-Bellido Proc. Natl. Acad. Sci. USA 93 (1996) molecules (polypeptides and polynucleotides) that have frozen At the next higher or organismic level of biological com- their structural symmetry. plexity, we encounter creatures with bilateral, radial, or helical At the next higher level of biological complexity, we have symmetry. As a rule, bilaterally and helically symmetrical cell organelles and cells lipid–protein membranes, which sep- organisms are motile (swimming or walking) creatures, while arate internal from external aqueous phases and generate in radial symmetry is more often associated with sessile forms. principle isodiametric spheres with minimal surface energies. These symmetries are due to the orientation of the mitotic However, this symmetry is broken by the appearance of planes of the first zygotic divisions, which in turn may be anisotropies. Protista are polarized due to an asymmetric governed by an intrinsic polarity of the egg or by the entry point distribution of cytoskeletal proteins defining an anterior– of the sperm, thus defining an anterior–posterior axis andyor posterior axis, at the end of which in flagella (in bacteria) or a dorsal–ventral axis of symmetry. Subsequent cell divisions budding zones (in fungi and yeast) distinguish heads from tails. amplify these symmetries by iteration and linear segmentation. This head-to-tail polarity is defined by the intrinsic polarity of Radial cell cleavage gives rise to metamerism along the actin-like helical proteins or by the self-assembly of asymmet- circumference (as in polyps) while cleavage along two orthog- ric proteins complexes. Polarity based on molecular anisotropy onal axes gives rise to bilateral forms. Helical symmetry (as in and molecular recognition has template properties: original molluscs) results from modified radial cell cleavage retaining polarities guide the formation of subsequent ones. At the the helical staggering of successive zygotic divisions along the organelle level head–tail polarity retaining rotational symme- anterior–posterior axis. These symmetries must reflect simple try is a common feature of virus capsids. They result from the structural conditionants because they are easily modified by packing, by molecular matching, of anisotropic proteins, as in mutation. Helical forms of gastropods may have a clockwise or phage particles, with very few steric degrees of freedom. anticlockwise rotation different in closely related species and Alternatively, packing of identical anisotropic proteins gives mutation of particular genes can change the helical polarity of rise to tubes with helical rotational (left or right handed) the offspring. Bilaterally symmetrical organisms may have symmetry, as in virus capsids or flagella. secondary asymmetries