Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

Strand asymmetry in Candida genes
Malcolm McLean
Department of Molecular Genetics, Weizmann Institute of Science, Revohot, Israel
Genes of virtually all organisms have more A than T on the coding strand.
Additionally Candida albicans, in common with many unicellular fungi, shows a
distinct pattern of GC skew. The start of the gene, including the promoter region,
is enriched in C, the end of the gene is enriched in G. However the pattern is much
weaker in the model organisms, Saccharomyces cerevisiae and
Schizosaccharomyces pombe, which is probably why it has not been observed until
now. However similar AT and GC skews have been found in other organisms, and
the standard explanation is mutational pressure. Roughly, the strands are in different
environments when being duplicated or transcribed, and thus accumulate different
mutations.
However it is hard to account for a change of sign of GC skew with the mutational
pressure hypothesis. Furthermore, analysis of recent substitution and indel
mutations, obtained by aligning homologous genes from related species, does not
support mutational pressure as the force maintaining the GC skew. We instead
propose a selective hypothesis. CTP is the nucleotide tri-phosphate with the
smallest pool. We propose that CTP loading is a rate-limiting step in RNA pol II
elongation (the biochemical evidence is ambiguous), and that a gradient of
decreasing C and increasing G in the mRNA transcript reduces the possibility of
RNA pol II traffic jams in highly transcribed genes.
We are grateful to the European Commission for funding the FINSysB Marie Curie Initial Training Network
(PITN-GA-2008-214004).
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