Genomes and Genomics 3 Techsession 7 2007

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Molecular Phylogenetic Analysis:

Horizontal Gene Transfer, or

Are there bugs in our genome?

Mark Blaxter

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3: 4: The N-acetylneuraminate lyase gene from Homo sapiens (Hs-anl)

What do N-acetylneuraminate lyases do?

They are enzymes that "catalyze the condensation of N-acetyl-D-mannosamine and pyruvate to form (the amino-sugar) N-acetylneuraminate. They are related in sequence (and structure) to dihydropicolinate synthases (DHDPS). DHDPS is the key enzyme in lysine biosynthesis via the diaminopimelate pathway of prokaryotes, some phycomycetes and higher plants." (text from Sanger Institute pFam).

The aminosugar biosynthesis pathway is presented in a browsable format via the Kyoto Encyclopaedia of Genes and Genomes (KEGG). Go to

http://www.genome.jp/dbget-bin/show_pathway?ot00530+ko:

The coloured boxes show the enzymes: they are named by their Enzyme Commission codes. For N-acetylneuraminate lyases the code is E4.1.3.3. The image is available as a local copy (without all the hyperlinks to the KEGG database) here.

What does the human N-acetylneuraminate lyase gene look like?

The human gene was identified by the genome sequencing and annotation teams after it was predicted automatically by their gene-finding programs: see the ENSEMBL genome browser at

http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000135838

Have a look at the page linked above. You will see that the gene has a number of exons, which are spliced in the premRNA to form the mature mRNA that is translated. These spliced introns definitively mark the gene as being of eukaryotic origin (and not a bit of bacterial DNA that got into the sequencing pipeline).

(The human N-acetylneuraminate lyase gene is also available in NCBI Entrez at

http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=protein&val=55960468 )

The protein sequence is as follows:

   

      

         
>ENST00000258317 pep:known chromosome:NCBI35:1:179495142:179530245:1
MAFPKKKLQGLVAATITPMTENGEINFSVIGQYVDYLVKEQGVKNIFVNGTTGEGLSLSV
SERRQVAEEWVTKGKDKLDQVIIHVGALSLKESQELAQHAAEIGADGIAVIAPFFLKPWT
KDILINFLKEVAAAAPALPFYYYHIPALTGVKIRAEELLDGILDKIPTFQGLKFSDTDLL
DFGQCVDQNRQQQFAFLFGVDEQLLSALVMGATGAVGSTYNYLGKKTNQMLEAFEQKDFS
LALNYQFCIQRFINFVVKLGFGVSQTKAIMTLVSGIPMGPPRLPLQKASREFTDSAEAKL
KSLDFLSFTDLKDGNLEAGS
      
   

For more information on this enzyme/gene family, see also:

The protein families database Pfam

http://www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF00701

NCBI Clusters of orthologous genes database (COG)

http://www.ncbi.nlm.nih.gov/COG/new/release/cow.cgi?cog=COG0329

The Kyoto Encyclopaedia of Genes and Genomes (KEGG) entry for acetylneuraminate lyase showing its place in amino-sugar metabolism

http://www.genome.jp/dbget-bin/www_bget?ko+K01639

 

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