Abstract
The uroporphyrinogen III synthase (UROS) enzyme (also known as hydroxymethylbilane hydrolyase) catalyzes the cyclization of
hydroxymethylbilane to uroporphyrinogen III during heme biosynthesis. A deficiency of this enzyme is associated with the very
rare Gunther's disease or congenital erythropoietic porphyria, an autosomal recessive inborn error of metabolism. The current
study investigated the possible role of UROS (Homo sapiens [EC: 4.2.1.75; 265 aa; 1371 bp mRNA; Entrez Pubmed ref NP_000366.1,
NM_000375.2]) in evolution by studying the phylogenetic relationship and divergence of this gene using computational methods.
The UROS protein sequences from various taxa were retrieved from GenBank database and were compared using Clustal-W
(multiple sequence alignment) with defaults and a first-pass phylogenetic tree was built using neighbor-joining method as in
DELTA BLAST 2.2.27+ version. A total of 163 BLAST hits were found for the uroporphyrinogen III synthase query sequence and
these hits showed putative conserved domain, HemD superfamily (as on 14
th
Nov 2012). We then narrowed down the search by
manually deleting the proteins which were not UROS sequences and sequences belonging to phyla other than Chordata were
deleted. A repeat phylogenetic analysis of 39 taxa was performed using PhyML and TreeDyn software to confirm that UROS is a
highly conserved protein with approximately 85% conserved sequences in almost all chordate taxons emphasizing its importance
in heme synthesis.