Correlating Transcription and Cell Cycle

Source: Klevecz, R.R., Bolen, J., Forrest, G., and Murray, D.B. A genomewide oscillation in transcription gates DNA replication and cell cycle. 2004. PNAS, 101(5): 1200-5

The authors measured transcript abundance as it fluctuated with changes in dissolved oxygen content for yeast. They found that there were three timepoints were gene expression peaked: two peaks with >2,000 genes reaching their maximum expression when oxygen levels were high (cells nonrespiring) and one peak where 650 genes reached their maximum expression when oxygen levels were low (cells respiring). Compared transcripts to states, and found that mitochondrial genes are expressed during reductive phase when mitochondrial function is minimal; while sulfur metabolism genes are expressed in respiratory phase right before they are needed for DNA replication in beginning of reductive phase. Most periods were ~40 minutes, and other studies showed that on a variety of media the doubling times of yeast were some multiple of 40 minutes.



•Other notes:
-cell-to-cell synchronization involved through respiratory inhibition by H2S and phase shifts due to acetaldehyde
-87% of genes expressed maximally in reductive phase
=2400 early, 2200 late
-650 genes maximum expression in oxidative phase
-4-12 minute lag between transcript peak and maximum gene product function
-DNA replication begins abruptly at end of respiration, H2S levels rise
-separation in time between oxidative and reductive phases goes to transcript levels and is coordinated with DNA replication
=prevents oxidative stress

Small Phenotypes - Large Number of Loci

Source: Brem, R.B. and Kruglyak, L. The landscape of genetic complexity across 5,700 gene expression traits in yeast. 2005. PNAS, 102 (5): 1572-7

The authors measured transcript abundance between BY4716 and RM11-1a yeast strains as well as their segregants to do QTL mapping. Over half the transcripts linked to a QTL, but extensive modeling showed that most traits would have multiple loci and no single locus would have a large effect. The authors limited the transcripts they looked at based on heritability scores. They also did a breakdown of inheritance patterns for the phenotypes and concluded that an overwhelming proportion are inherited in a transgressive segregation manner as compared to an additive effect. A small but nontrivial were found to be epistatically inherited, and most were in the transgressive segregation camp.

Other notes:
-median heritability was 27%
-no QTLs detected for nearly 40% of highly heritable transcripts
-only 3% of highly heritable transcripts have single-locus inheritance, 17-18% for one or two loci, over half for at least five loci
-11% had directional model (phenotype of one parent)
-59% were transgressive segregation (outside parental range)
-16% epistatic (tests difference between means of segregants and parents)
-“opposing QTLs may be a mechanism for generating diversity in subsequent generations”


Left: Directional; Center: Transgressive; Right: Epistatic




Damn you genetic complexity!