Homology Can We Get It Right

Thus far, I have discussed sequence similarity without using the word homology. This cannot last much longer. All organisms on Earth are thought to descend from the common ancestor (discussed further in Chapter 13), and when two organisms have a common trait, this is often because the trait has been inherited by both species from an ancestor either the distant ancestor of all organisms or, more likely, a more recent ancestor of the two organisms. Walter Fitch (1970b, 2000) defined homology as...

E

The conceptual evolutionary path from an all-beta to an all-alpha protein (A) C-terminal domain of alpha-amylase (PDB ID 1BPL) (B) C-terminal domain of G4-amylase (2AMG) (C) N-terminal domain of the gamma subunit of glycogen phosphorylase kinase (1PHK) (D) N-terminal signaling domain of sonic hedgehog (1VHH) (E) C-terminal domain of catabolite gene activator protein (1CGP) (F) N-terminal domain of biotin repressor (1BIA) (G) C-terminal domain of ribosomal protein L11 (1FOW) (H)...

Fa

Where N is the number of mesofolds, and D' is the mean number of families per mesofold. Most of the parameter fitting, however, is done using Orengo etal.'sFA of 23,100, and at that point the total number of folds is 4600. Clearly, the value of FA is of the utmost importance for all other computation. However, I suspect that 23,100 is an overestimation of FA, and the brief explanation by Coulson and Moult as to why they switched to a twofold higher FA is confusing to me. In 2000, Yuri Wolf,...

Getting Ready for the Era of Comparative Genomics The Importance of Viruses

Virologists like to recollect the episodes in the history of science in which viruses played an important role. Max Delbruck and the Phage Group at Cold Spring Harbor Laboratory is the most famous example (Phage and the Origins of Molecular Biology, 2006). Many other fundamental discoveries in molecular biology were facilitated by the simplicity of viral genetic systems, with their limited number of tractable molecular components. This includes the Hershey and Chase experiment on phage T4...

Annotations by Homology and Errors Inherent in the Process

Bork and Koonin (1998), Devos and Valencia (2003), Park et al. (2005), Green and Karp (2005), and others studied several types of mistakes that are common when annotation is transferred from a database entry to an uncharacterized homolog. In effect, there are three groups of errors. First, the homology may be inferred incorrectly either true homologs are not found or unrelated proteins are taken for homologs. Second, the homologs may be found correctly, but the orthologs and paralogs may be...

Homology and Orthology How to Use Them for Prediction of Protein Function and What Can Go Wrong

As discussed in Chapter 3, two orthologs, one in each of two species, are more likely to have the same molecular function, and the same biological function, than two paralogs. Paralogs are more likely to evolve new, if related, functions. This has been called the principle of phyloge-nomic by Zmasek and Eddy 2002 . As an aside,phylogenomics is a term coined by Jonathan Eisen 1998 to summarize the idea that the evolutionary tree can help us understand how biological functions are distributed...

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S.FAFGVVLLEI YSFGVVLLEL YSYGVMLLEI FSFGVLLLEI YSFGVVLLEL JSYGILMWEI JSFGILLWEI aE Figure 2.4. The alleged plant connexin is in fact a member of the protein kinase family. Multiple alignment of CX32 with selected protein kinase sequences. Residues shared by CX32 and other sequences one exception in kinases allowed in the bottom of the figure are indicated by asterisks. Alignment to kinases is supported by BLAST statistics, by the conservation of known or predicted secondary structure elements,...

Detection of DOGs Using Phyletic Patterns and Phytogeny

Homology, analogy, and DOGs exist regardless of our ability to detect them. The DOGs we have discovered are most likely only a fraction of all DOGs that have occurred in evolution. How can we recognize a DOG, and how many of them remain undetected There are two prerequisites for finding a DOG. First, there has to be empirical evidence that similar molecular function is present in two lineages. Second, there has to be a way to robustly define orthologs and to assert their absence. The latter is...