Identification of a core set of signature cell cycle genes whose relative order of time to peak expression is conserved across species

Abstract

A cell division cycle is a well-coordinated process in eukaryotes with cell cycle genes exhibiting a periodic expression over time. There is considerable interest among cell biologists to determine genes that are periodic in multiple organisms and whether such genes are also evolutionarily conserved in their relative order of time to peak expression. Interestingly, periodicity is not well-conserved evolutionarily. A conservative estimate of a number of periodic genes common to fission yeast (Schizosaccharomyces pombe) and budding yeast (Saccharomyces cerevisiae) ('core set FB') is 35, while those common to fission yeast and humans (Homo sapiens) ('core set FH') is 24. Using a novel statistical methodology, we discover that the relative order of peak expression is conserved in ∼80% of FB genes and in ∼40% of FH genes. We also discover that the order is evolutionarily conserved in six genes which are potentially the core set of signature cell cycle genes. These include ace2 (a transcription factor) and polo-kinase plo1, which are well-known hubs of early M-phase clusters, cdc18 a key component of pre-replication complexes, mik1 which is critical for the establishment and maintenance of DNA damage check point, and histones hhf1 and hta2.

Figure 1.

Conservation of periodicity and phase. In each panel, the vertical hash mark on the time axis represents the boundary of a phase.

Figure 2.

(I) Relative order of peak expression of genes A,B and C is not conserved in Species 1 and 2. (II) Relative order of peak expression of genes D, E and F is conserved in Species 1 and 2. Orthologs in Species 2 are denoted by lower case letters a, b, c, d, e and f. In each panel, the vertical hash mark on the time axis represents the boundary of a phase. Insets in each panel represent the time to peak expression in terms of phase of cell cycle.

Figure 3.

Saccharomyces pombe genes arranged according to the relative order and approximate locations of their S. cerevisiae orthologs (in parenthesis). Sectors drawn are according to S. pombe cell cycle.

Figure 4.

A core set of signature cell cycle genes with relative order of time to peak expression conserved among S. pombe, S. cerevisae and H. sapiens. Sectors and approximate locations of genes are drawn according to S. pombe. S. pombe genes are in green, S. cerevisiae orthologs are in red and H. sapiens orthologs are in blue.