Expression of Tetrahymena histone H4 in yeast.

Histone H4 is one of the most conserved proteins known. The very low rate of nonsynonymous substitution in H4 suggests that it fulfills an essential function in virtually all eukaryotes. While the majority of histone H4 sequences differ only slightly from the general consensus H4 sequence, yeast and Tetrahymena sequences diverge substantially from both the consensus and from each other. This study demonstrates that despite this divergence, when Saccharomyces cerevisiae cells are forced to use the Tetrahymena thermophila histone H4 protein, they are viable although they have a reduced growth rate, are temperature-sensitive relative to wild-type, have a lengthened G2 phase, and show a dramatic repression of mating. An amino acid replacement at position 33 in the protein improves the growth rate of these cells growing at temperatures above 28 degrees C. This replacement changes a proline to a serine and is a further divergence from both the Tetrahymena thermophila and Saccharomyces cerevisiae histone H4 sequences. Thus, the replacement and expression of a non wild-type histone H4 in yeast offers measurable effects on cell growth, identifying amino acids required for optimal yeast functioning.