![]() ![]() ![]() Our results describe general features of the evolution of protein function, and serve as a guide to the reliability of annotation transfer, based on the closeness of the relationship between a new protein and its nearest annotated relative.Īssignment of function to gene products in the absence of direct experimental information is an important challenge of computational molecular biology. This means that for very similar proteins (about 50 % identical residues) the chance of completely incorrect annotation is low however, because of the phenomenon of recruitment, it is still non-zero. For proteins with more than 50% residue identity, transfer of annotation between homologs will lead to an erroneous attribution with a totally dissimilar function in fewer than 6% of cases. Our results show that, among homologous proteins, the proportion of divergent functions decreases dramatically above a threshold of sequence similarity at about 50% residue identity. We correlated the divergence in sequences determined from pairwise alignments, and the divergence in function determined by path lengths in the Gene Ontology graph, taking into account the fact that many proteins have multiple functions. Within families there is a broad range of sequence similarity from very closely related proteins – for instance, orthologs in different mammals – to very distantly-related proteins at the limit of reliable recognition of homology. We determined the relationship between sequence divergence and function divergence in 6828 protein families from the PFAM database. Here, we present a quantitative study of sequence and function divergence, based on the Gene Ontology classification of function. The assumption that homologs share function – the basis of transfer of annotations in databases – must therefore be regarded with caution. Again, these domains cannot function when internal to a coding region, and are termed Tail domains.įor more details on protein domains including how to assemble protein domains into protein coding sequences, please see Protein domains.The relationship between divergence of amino-acid sequence and divergence of function among homologous proteins is complex. Other special features, such as degradation tags, are also required to be at the extreme C-terminus. Similarly, the C-terminal domain of a protein is special, containing at least a stop codon.Certain Internal domains have particular functions in protein cleavage or splicing and are termed Special Internal domains. Since these protein domains are within a protein coding sequence, they are called Internal domains. The DNA sequence of such domains must maintain in-frame translation, and thus is a multiple of three bases. A protein domain is a sequence of amino acids which fold relatively independently and which are evolutionarily shuffled as a unit among different protein coding regions.These occur at the beginning of a coding region, and therefore are termed Head domains. Second, many coding regions have special features at the N terminus, such as protein export tags and lipoprotein cleavage and attachment tags. First, it always contains a start codon, spaced at an appropriate distance from a ribosomal binding site. The N-terminal domain of a protein coding sequence is special in a number of ways.Thus, a protein coding sequence could either be entered as a basic part or as a composite part of two or more protein domains. Protein coding sequences are often abbreviated with the acronym CDS.Īlthough protein coding sequences are often considered to be basic parts, in fact proteins coding sequences can themselves be composed of one or more regions, called protein domains. In the Registry, protein coding sequences begin with a start codon (usually ATG) and end with a stop codon (usually with a double stop codon TAA TAA). ![]() Therefore some protein coding sequences may be optimized for use in a particular chassis. In some cases, different chassis may either map a given codon to a different sequence or may use different codons more or less frequently. Every three nucleotides, termed a codon, in a protein coding sequence encodes 1 amino acid in the polypeptide chain. Protein coding sequences are DNA sequences that are transcribed into mRNA and in which the corresponding mRNA molecules are translated into a polypeptide chain. ![]()
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