Origins of Life and Evolution of Biospheres

, Volume 43, Issue 4–5, pp 363–375 | Cite as

Norvaline and Norleucine May Have Been More Abundant Protein Components during Early Stages of Cell Evolution

  • Claudia Alvarez-Carreño
  • Arturo Becerra
  • Antonio LazcanoEmail author
Protein Evolution


The absence of the hydrophobic norvaline and norleucine in the inventory of protein amino acids is readdressed. The well-documented intracellular accumulation of these two amino acids results from the low-substrate specificity of the branched-chain amino acid biosynthetic enzymes that act over a number of related α-ketoacids. The lack of absolute substrate specificity of leucyl-tRNA synthase leads to a mischarged norvalyl-tRNALeu that evades the translational proofreading activites and produces norvaline-containing proteins, (cf. Apostol et al. J Biol Chem 272:28980–28988, 1997). A similar situation explains the presence of minute but detectable amounts of norleucine in place of methionine. Since with few exceptions both leucine and methionine are rarely found in the catalytic sites of most enzymes, their substitution by norvaline and norleucine, respectively, would have not been strongly hindered in small structurally simple catalytic polypeptides during the early stages of biological evolution. The report that down-shifts of free oxygen lead to high levels of intracellular accumulation of pyruvate and the subsequent biosynthesis of norvaline (Soini et al. Microb Cell Factories 7:30, 2008) demonstrates the biochemical and metabolic consequences of the development of a highly oxidizing environment. The results discussed here also suggest that a broader definition of biomarkers in the search for extraterrestrial life may be required.


Norvaline Norleucine Prebiotic amino acids Misincorporation of norvaline and norleucine in proteins Aminoacyl-tRNA synthases 



Support of the Posgrado en Ciencias Biomédicas, UNAM, to CAC is gratefully acknowledged. We are indebted to an anonymous reviewer for many kind suggestions. Part of the work reported here was completed during a sabbatical leave of absence of AB, with support of DGAPA-UNAM, where he enjoyed the hospitality of Professor Juli Peretó at the Instituto Cavanilles (Valencia, Spain).


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Claudia Alvarez-Carreño
    • 1
  • Arturo Becerra
    • 1
  • Antonio Lazcano
    • 1
    Email author
  1. 1.Facultad de CienciasUniversidad Nacional Autonoma de MexicoMexico D.FMexico

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