Codon Switching of Conserved Ser Residues in Coagulation and Fibrinolytic Proteases

Overview

Journal J Thromb Haemost

Publisher Elsevier

Specialty Hematology

Date 2024 May 31

PMID 38821294

Authors

Bosko M Stojanovski

Enrico Di Cera

Affiliations

Soon will be listed here.

Abstract

Background: Unique among all amino acids, Ser is encoded by 2 sets of codons, TCN and AGY (N = any nucleotide, Y = pyrimidine), that cannot interconvert through single nucleotide substitutions. Both codons are documented at the essential residues S195 and S214 within the active site of serine proteases. However, it is not known how the codons interconverted during evolution because replacement of S195 or S214 by other amino acids typically results in loss of activity.

Objective: To characterize the prevalence of codon switching among essential and non-essential Ser residues in coagulation and fibrinolytic proteases from different vertebrate lineages.

Methods: TCN and AGY codon usage was analyzed in >550 sequences.

Results: Evolutionary pressure to preserve the codon of S195 is absolute, with no evidence of interconversion. Pressure to preserve the codon of S214 is also strong, but an AGY↔TCN interconversion is observed in factor VII-inactive and protein C from ray-finned fish. In both cases, the interconversion occurred in genes that were rapidly evolving. In contrast, codon switching at nonessential Ser residues in the kringle domains of coagulation and fibrinolytic proteases is quite common and could be identified in half of the kringles analyzed.

Conclusion: Codon interconversion of essential Ser residues of coagulation and fibrinolytic proteases only occurred in genes that were rapidly evolving and that-at least in some cases-evolved following genome duplication. Interconversion is common at nonessential Ser residues as found in kringle domains.

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