What is the difference between biochemical and biological function?

A substantial fraction of almost every genome sequenced consists of genes that have no known function and that do not have sequence similarity to any genes with known function. How would your approach change if the genes of unknown function were in the human genome?

A substantial fraction of almost every genome sequenced consists of genes that have no known function and that do not have sequence similarity to any genes with known function. Describe two approaches to ascertaining the biological role of these genes in S. cerevisiae.

In conducting the study described in Problem 24, you have noted that a set of S. cerevisiae genes are repressed when yeast are grown under high-salt conditions. How might you approach this question if genome sequences for the related Saccharomyces species S. paradoxus, S. mikatae, and S. bayanus were also available?

Using the two-hybrid system to detect interactions between proteins, you obtained the following results: A clone encoding gene A gave positive results with clones B and C; clone B gave positive results with clones A, D, and E but not C; and clone E gave positive results only with clone B. Another clone F gave positive results with clone G but not with any of A–E. Can you explain these results? To follow up your two-hybrid results, you isolate null loss-of-function mutations in each of the genes A–G. Mutants of genes A, B, C, D, and E grow at only 80% of the rate of the wild type, whereas mutants of genes F and G are phenotypically indistinguishable from the wild type. You construct several double-mutant strains: The ab, ac, ad, and ae double mutants all grow at about 80% of the rate of the wild type, but af and ag double mutants exhibit lethality. Explain these results. How do the two-hybrid system and genetic interaction results complement one another? Can you reconcile your two-hybrid system and genetic interaction results in a single model?

Mutations in the Drosophila Ultrabithorax (Ubx) gene result in wings developing from two thoracic segments, rather than just one as in wild-type flies. In the mouse genome there are two Ubx orthologs . How would you determine whether the two mouse genes have distinct or redundant functions?

Although a single activator may bind many enhancers in the genome to control several target genes, in many cases, the enhancers have some sequence conservation but are not all identical. Keeping this in mind, consider the following hypothetical example:

- Undifferentiated cells adopt different fates depending on the concentration of activator protein, Act1.

- A high concentration of Act1 leads to cell fate 1, an intermediate level leads to cell fate 2, and low levels to cell fate 3.

- Research shows that Act1 regulates the expression of three different target genes (A, B, and C) with each having an enhancer recognized by Act1 but a slightly different sequence that alters the affinity of Act1 for the enhancer. Act1 has a high affinity for binding the enhancer for gene A, a low affinity for the gene B enhancer, and an intermediate affinity for the gene C enhancer.

From these data, speculate on how Act1 concentrations can specify different cell fates through these three target genes? Furthermore, which target genes specify which fates?

Hereditary spherocytosis (HS) is a disorder characterized by sphere-shaped red blood cells, anemia, and other abnormal traits. Ankyrin-1 (ANK1) is a protein that links membrane proteins to the cytoskeleton. Loss of this activity is associated biochemically to HS. However, Gallagher et al. (2010) (J. Clin. Invest. 120:4453–4465) show that HS can also be caused by mutations within a region from -282 to -101 relative to the transcriptional start site, which lead to constitutive transcriptional repression in erythroid cells due to local chromatin condensation. Propose a hypothesis for the function of the -282 to -101 region of the ANK1 gene.