Help: Of mice and men: LIS1 protein
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
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
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):
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