Journal of Molecular Evolution

, Volume 86, Issue 5, pp 255–263 | Cite as

Chiral Monomers Ensure Orientational Specificity of Monomer Binding During Polymer Self-Replication

  • Hemachander SubramanianEmail author
  • Robert A. Gatenby
Original Article


Biomolecular homochirality is universally observed in living systems but the molecular and evolutionary dynamics that led to its emergence are unknown. In fact, there are significant disadvantages in using chiral monomers for polymerization, which include enantiomeric cross-inhibition in racemic medium and under-utilization of available resources for self-replication in the primordial environment. Nevertheless, most investigations of homochirality in living systems assume that the individual primordial monomers were chiral prior to the formation of self-replicating polymer and therefore focus on identifying a symmetry-breaking mechanism that might choose one enantiomer over the other in a racemic medium. Within the premise that the extant biomolecules are products of molecular evolution, we ask a related but distinct question: why is an achiral monomer molecule disfavored? Here we identify an evolutionary advantage for molecular evolution to choose chiral over achiral monomers to construct primordial self-replicating polymers. We argue that when polymerization is constrained to proceed in only one direction along the template, as in DNA, evolution favors chiral monomers and homochiral polymers. This evolutionary advantage stems from the ability of a chiral monomer to bond with the template in only one orientation relative to the template monomer, along the direction of polymerization. An achiral monomer, on the other hand, offers more than one possible orientation for bonding with the template monomer, due to the presence of symmetry elements in its structure, which would lead to inhibition of polymerization. We show that the requirement of orientational specificity leads to monomer chirality, by using a known relationship between rotational and reflection symmetry elements, within the constraint that the resultant polymers are helical.


Biomolecular chirality Orientational specificity DNA strand directionality Monomer rotation and reflection symmetries 



Support for this work was provided by the Moffitt Physical Science and Oncology Network (PS-ON) NIH grant, U54CA193489. We thank Gerald Joyce, Antonio Lazcano, Addy Pross, John Cleveland, Joel Brown, Christopher Whelan, and Robert Gillies for useful comments. HS thanks Artem Kaznatcheev, IMO faculty, and post-doctoral associates for helpful discussions.

Conflict of interest

The authors declare no competing financial interests.


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Authors and Affiliations

  1. 1.Integrated Mathematical Oncology DepartmentH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  2. 2.Integrated Mathematical Oncology Department and Cancer Biology and Evolution ProgramH. Lee Moffitt Cancer Center and Research InstituteTampaUSA

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