This set of Basic Bioinformatics Questions and Answers focuses on “The Use of Gene Order & Phylogeny to Predict Protein – Protein Interactions”.
1. Experimentation is most desirable over computational methods by every means.
a) True
b) False
View Answer
Explanation: Computational methods for predicting protein-protein interactions are desirable as experimental determination is time-consuming and expensive. Several prediction methods are based on the observation that if two proteins are part of the same complex, it is favorable for the two interaction partners to be co-expressed and co-regulated.
2. Interactions between proteins can be predicted computationally by looking for sets of genes that occur as a _______
a) single gene in at least one genome
b) multiple genes in at least one genome
c) multiple genes in various genomes
d) single gene in various genomes
View Answer
Explanation: Interactions between proteins can be predicted computationally by looking for sets of genes that occur as a single gene in at least one genome. Or it can be done by looking for prokaryotic genes that have conserved adjacent gene order across several genomes.
3. Genes that are consistently part of the same operon across different, distantly related genomes are likely to be part of the same protein complex or functional process across all species.
a) True
b) False
View Answer
Explanation: This is because they have been selected to remain as a co-regulated unit throughout the extensive shuffling of gene order that takes place in prokaryote genomes. Thus conservation of gene order across different, distantly related genomes has been used as a method for predicting protein interactions.
4. When comparing pairs of genes or sets of genes in different genomes for this purpose, it is not mandatory for the genes to be orthologs.
a) True
b) False
View Answer
Explanation: When comparing pairs of genes or sets of genes in different genomes for this purpose, it is important to ensure that the genes are truly equivalent, in other words that they are orthologs, as opposed to merely similar genes. This is frequently done by only accepting a pair of proteins as orthologs if they are ‘bi-directional best hits’. This means that both proteins are the best match to each other when searching against the other proteome. The other extreme would be to consider proteins as equivalent if they share just one of many domains, for instance.
5. Members of a stable complex are often co-regulated and thus will be detected by the method of Conservation of gene order.
a) True
b) False
View Answer
Explanation: As much it is true proteins which are part of the same metabolic pathway or part of the same biological process can also be co-regulated. Therefore, although some of the genes detected as interacting by this method physically interact, others are just functionally associated with each other.
6. In a quantitative assessment of this method (Conservation of gene order) using the genome of the parasitic organism Mycoplasma genitalium as a benchmark.
a) True
b) False
View Answer
Explanation: Huynen and colleagues found that two-thirds to four-fifths of the general interactions detected correspond to physical interactions and another 13% correspond to a metabolic or non-metabolic pathway. Genes those are physically associated with each other while being regulated and expressed individually will not be detected by this method.
7. Conservation of gene order due to operon structure is _______ so interactions of proteins specific to eukaryotes cannot be detected by method of Conservation of gene order.
a) not applicable to archea genomes
b) not applicable to prokaryote genomes
c) applicable to eukaryote genomes
d) not applicable to eukaryote genomes
View Answer
Explanation: Co-regulation of genes in eukaryotes can be inferred by similarity in the expression patterns of genes. A comparison of co-expressed yeast and worm genes showed that 90% of those pairs of genes with conserved co-expression are members of stable complexes. Thus, the principle of conserved co-regulation across distantly related organisms applies to stable complexes in both prokaryotes and eukaryotes, and can be used as a prediction tool in both.
8. An approach for predicting ______ to look for cases across a set of genomes where _____ are part of the same gene in one genome resulted in gene fusion method.
a) gene interactions, only three to four orthologs
b) gene interactions, two orthologs
c) protein interactions, two or more orthologs
d) protein interactions, two orthologs
View Answer
Explanation: The prediction is then that the orthologs that are on separate genes in the other genomes interact with each other. In the case of gene fusion, the fused proteins are not only co-regulated, as in conservation of gene order described above, but also permanently colocalized in the cell. The additional requirement of colocalization beyond just co-regulation poses a further limitation on the prediction method.
9. Domains that are part of a multidomain protein are ______
a) nethier co-regulated nor colocalized
b) not co-regulated but colocalized
c) co-regulated and but not colocalized
d) co-regulated and colocalized
View Answer
Explanation: Therefore, members of stable complexes as well as consecutive enzymes may be involved in gene fusions. However elements of signal transduction chains are seldom part of the same gene, for instance, as it is an essential part of their function that they can be regulated and localized independently.
10. Due to the requirement for co-regulation as well as colocalization, the method is mostly limited to certain classes of protein-protein interactions.
a) True
b) False
View Answer
Explanation: Those classes are members of the same stable complex and proteins in the same metabolic pathway. In their assessment of computational methods for prediction of all types of protein interactions, Huynen and colleagues found that two-thirds of the interactions detected in this way were between proteins that physically interact and another 15% between proteins part of the same metabolic pathway. The remaining interactions involved hypothetical proteins of unknown function.
11. The phylogenetic profile method relies on detection of orthologs (or homologs, in a variation of the method) in a set of genomes.
a) True
b) False
View Answer
Explanation: If the pattern of ortholog presence or absence is the same in a group of proteins, then these proteins are clustered together as belonging to the same functional class. A method that appears to reliably predict a loose functional correlation between proteins is the phylogenetic profile method developed by Pellegrini and colleagues.
12. In the assessment of methods to predict protein-protein interactions, one third of such pairs were found to physically interact, and an additional third to belong to the same metabolic pathway or functional process.
a) True
b) False
View Answer
Explanation: As mentioned, one third of such pairs were found to physically interact. The phylogenetic patterns of clusters of orthologous groups of proteins deposited in the COG database of Koonin and co-workers could in principle be used for prediction in the same way.
13. In the phylogenetic profile method for predicting protein interaction, presence or absence of orthologous genes is scored across a variety of genomes.
a) True
b) False
View Answer
Explanation: This is represented by presence or absence of a dot in the row. Genes that have the same pattern of presence or absence across genomes are predicted to interact.
14. Structural analyses on small sets of proteins have shown that the domains from a pair of families bind to each other with the same geometry in multi-domain proteins and in transient interactions.
a) True
b) False
View Answer
Explanation: Most domain families engage in interactions with one or two other types of families, but a few families are very versatile and interact with many families. These versatile families are ubiquitously useful families such as P-loop nucleotide triphosphate hydrolases and Rossmann domains.
15. The most detailed experimental information about protein-protein interactions comes from three-dimensional structures.
a) True
b) False
View Answer
Explanation: The 3-D structure gives the most conformation of the structure. It is likely that complexed protein structures will be solved more frequently in the wake of the structural genomics projects.
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