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.

Some advances in constrained inference for ordered circular parameters in oscillatory systems

“…It is interesting to note from Tables 1.3 and 1.4 that the partial orders derived by our methodology is satisfied by both species of yeast. Furthermore, this order is also satisfied by other previously published results (see Fernández et al (2012)). …”

“…As a consequence we may approximate the distribution of CT by the central F distribution instead of the chi-squared distribution. The proof of the theorem and other theoretical details of CT are given in Fernández et al (2012). Barragán et al (2013) where O * may be the partial order appearing in equation (1.3).…”

“…phase angle ϕ) of a cell-cycle gene, (c) comparing the phase angles of cell cycle genes across different experimental conditions or different organisms(cf. Bähler (2005), Jensen et al (2006), Fernández et al (2012)). A useful database containing results from various cell cycle microarray experiments is available at www.cyclebase.org, henceforth referred as cyclebase.…”

“…We illustrate the methodology described in this paper using the 34 cell cycle genes S. pombe genes and their S. cerevisiae orthologs/paralogs described in Fernández et al (2012). We used timecourse data available on ten experiments conducted on S. pombe in three labs (five by Rustici et al (2004), three Oliva et al (2005) and two by Peng et al (2005)) and six experiments conducted on S. cerevisiae in three labs (one experiment each by Cho et al (1998) andde Lichtenberg et al (2005), and two experiments each by Pramila et al (2006) and 2 by Spellman et al (1998)).…”

“…The R objects called SEXP are used in C++ to improve efficiency and execution time. The function cond.test executes the conditional test described in Fernández et al (2012) for the hypotheses (1.5). The methodology proposed to deal with the minimization problem (1.7) has also been implemented in R language as part of the new version of the isocir package.…”