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Toxicology and Industrial Health
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*Substance via MeSH
Hazardous Substances DB
*LEAD COMPOUNDS
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*Lead Poisoning
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research-article

Phylogenetic analysis of ALAD and MGP genes related to lead toxicity

AP Shaik

Research Wing, Indo-American Cancer Hospital and Research Centre, Banjara Hills, Hyderabad, Andhra Pradesh, India

M Khan

Research Wing, Indo-American Cancer Hospital and Research Centre, Banjara Hills, Hyderabad, Andhra Pradesh, India

K Jamil

Department of Genetics, Bhagwan Mahavir Medical Research Centre, Masab Tank, Hyderabad, Andhra Pradesh, India kaiser.jamil{at}gmail.com

Experimental studies in our laboratory have established the role of {delta}-aminolevulinic acid dehydratase (ALAD) and matrix {gamma}-carboxyglutamic acid (MGP) gene polymorphisms in the etiology of lead toxicity. Polymorphisms in these genes influenced the levels of lead in subjects exposed to this metal. In extension to our studies, we aimed to investigate the possible role of these proteins in evolution by studying the phylogenetic relationship and divergence of ALAD and MGP genes using computational phylogenetic methods. The human ALAD and MGP protein sequences from various species were retrieved from Swiss-Prot database and were compared using Basic Local Alignment Search Tool. Multiple sequence alignment was carried out using ClustalW with defaults, and phylogenetic trees for both the genes were built using neighbor-joining method as in Mega software. Our study indicated that ALAD is a highly conserved protein with the same metal binding site distributed in all the phyla (from archaea to chordates). Phylogenetic analysis of MGP gene revealed that it had an important role in the evolution of endogenous skeleton in contrast to exoskeleton of insects. Occurrence of these genes in evolution with conserved metal binding sites strengthens the role of ALAD and MGP genes in regulating heme biosynthesis and mineralization, respectively, in evolution and helps in better understanding of lead poisoning.

Key Words: ALAD • MGP • phylogeny • protein sequences

Toxicology and Industrial Health, Vol. 25, No. 6, 403-409 (2009)
DOI: 10.1177/0748233709106596


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