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Help: Of mice and men: LIS1 protein

Hulusi Cinar hcinar at nomvs.lsumc.edu
Mon Aug 7 19:11:44 EST 1995


        I do not know if this is the right forum for my question 
but I believe your 
comments would shed some light on the issue.

        Miller-Dieker lissencephaly syndrome (MDS) is a human 
developmental brain 
malformation caused by neuronal migration defects resulting in 
abnormal layering of the 
cerebral cortex. LIS1, the gene defective in MDS, encodes a 
subunit of brain platelet-
activating factor (PAF) acetylhydrolase which inactivates PAF, a 
molecule. One isoform of PAF acetylhydrolase present in bovine 
brain cortex is a 
heterotrimer comprising subunits with relative molecular masses 
of 45K, 30K and 29K . 
Hattori et al isolated the complementary DNA for the 45K subunit 
from the bovine brain. 
Sequence analysis revealed a striking identity (99%) of the 
subunit with the protein 
encoded by human LIS-1. The nucleotide sequence of the LIS-1 cDNA 
encoding the 
murine LIS-1 protein was also determined. The deduced protein 
shows a very high degree 
(99.8%) of homology with human LIS-1, having a single 
conservative amino acid (aa) 
change out of 410 aa.

        Here is the question: how can you explain 99% homology 
between human and 
murine LIS1 aa sequences? Is it usual or unusual from an 
evolutionary point of view? Any 
information or comment is invaluable. Relevant references are 
also helpful. Thank you.


1. Peterfy M. Gyuris T. Basu R. Takacs L. Lissencephaly-1 is one 
of the most conserved proteins between 
mouse and human: a single amino-acid difference in 410 residues. 
Gene 1994 Dec 15; 150(2): 415-6.  

2. Reiner O. Albrecht U. Gordon M. Chianese K A. Wong C. Gal- 
Gerber O. Sapir T. Siracusa L D. 
Buchberg A M. Caskey C T. Lissencephaly gene (LIS1) expression in 
the CNS suggests a   
    role in neuronal migration. J Neurosci 1995 May; 15(5 Pt 2): 

3. Hattori M. Adachi H. Tsujimoto M. Arai H. Inoue K. 
Miller-Dieker lissencephaly gene encodes a 
subunit of brain platelet-activating factor acetylhydrolase 
<corrected> <published erratum appears in 
Nature 1994 Aug 4; 370(6488):391>. Nature 1994 Jul 21; 370(6486): 

Hulusi Cinar.

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