Sequence homology

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Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two sequences are said to be homologous if they are both derived from a common ancestral sequence

Homology among DNA, RNA, or proteins is typically concluded from their nucleotide or amino acid sequence similarity. Significant similarity is strong evidence that two sequences are related by evolutionary changes from a common ancestral sequence. Alignments of multiple sequences are used to show which regions of each sequence are homologous.

Protein and DNA homology analyses can lie performed with BLAST programs. Structural analysis of mRNA can be performed with the mfold and SECISearch programs.

However, homologous sequences do not always share significant sequence similarity, there are thousands of homologous protein alignments that are not significant, but are clearly homologous based on statistically significant structural similarity or strong sequence similarity to an intermediate sequence.

Homologous sequences have similar structures, and frequently, they have similar functions as well. But the relationship between homology and function is less predictable, both because a single protein structure can have multiple functions and because the concept of “function” is more ambiguous.

Homology shows an ancient common origin and temporal evolution and refers to structural characteristics. In comparative anatomy, it is used to compare structures in different animal species.

Homologous sequences are orthologous if they are inferred to be descended from the same ancestral sequence separated by a speciation event, when a species diverges into two separate species, the copies of a single gene in the two resulting species are said to be orthologous.

Paralogous genes are genes that are related through duplication events in the last common ancestor of the species being compared.

Ohnologous genes are paralogous genes that have originated by a process of 2R whole-genome duplication. Ohnologues are useful for evolutionary analysis because all ohnologues in a genome have been diverging for the same length of time

Homologs resulting from horizontal gene transfer between two organisms are termed xenologs. Xenologs can have different functions if the new environment is vastly different for the horizontally moving gene.

Homology forms the basis of organization for comparative biology. A homologous trait is often called a homolog. In genetics, the term “homolog” is used both to refer to a homologous protein and to the gene (DNA sequence) encoding it. Homology among proteins or DNA is often incorrectly concluded on the basis of sequence similarity. As with anatomical structures, high sequence similarity might occur because of convergent evolution, or, as with shorter sequences, because of chance. Such sequences are similar, but not homologous. Sequence regions that are homologous are also called conserved.

Sequence homology search tools may be divided into four groups;

Pairwise searches such as BLAST, Smith-Waterman. These programs compare a single query sequence against each sequence in a (large) database and report significant similarities.

Profile searches such as HMMER. These programs, if supplied with, any examples of a family of sequences, will attempt to construct a profile of this family, then search a database for sequences that fit the profile.

Automated searches such as PSI-BLAST. These programs first seek out close relatives of a single query sequence, then use these close relatives to build a profile. In other words, they combine the tasks performed by pairwise and profile search tools.

Protein family databases such as PFAM, PROSITE and BLOCKS. Here, a single query sequence is compared to entries in a database of profiles, each representing a distinct protein family. This approach shares many of the benefits of profile searches, without the duplicated effort of finding members of an already well-characterized family.

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