Microcephaly: tracing the evolutionary lineage of ASPM gene.

Abstract

Objective: Microcephaly, in the form of congenital autosomal recessive disorder (MCPH), is characterized by the reduced occipital frontal head circumference >3 standard deviation of otherwise normal population of matching age and sex. The disease is primarily associated with mild to severe mental retardation. Earlier studies have unravelled that among Pakistan population, mutations in ASPM gene is strongly associated in MCPH. 

Experimental Methods: cDNA gene and protein sequences of ASPM gene were retrieved from NCBI database and subjected to the non-redundant BLAST. Consensus phylogenetic tree was developed after multiple sequence alignment and bootstrapping of the protein sequences of ASPM gene from different mammals using Neighbour Joining method, selecting non mammals as an out group. Comparisons of the gene synteny and exon and intron patterns of ASPM gene were also undertaken to investigate chromosomal changes during the course of human evolution. Different statistical evolutionary models namely, 

Results: Phylogenetic tree based on ASPM gene clearly segregated all non mammalian members as an out group. Mammalian in group holds the established evolutionary lineage, based on morpho-genetic attributes of mammalian evolution, segregating monotremes at the beginning followed by the members of rodentia and finally radiation of the primates including humans. Orientation of the ASPM gene remains conserved between human and chimpanzee, however, it was found reversed along with the flanking genes, a zinc finger binding domain 41 and coagulation factor XIII, which suggest relatively recent event of gene inversion.