title: Single Amino Acid Repeats in the Proteome World: Structural, Functional, and Evolutionary Insights.
abstract: Microsatellites or simple sequence repeats (SSR) are abundant, highly diverse stretches of short DNA repeats present in all genomes. Tandem mono/tri/hexanucleotide repeats in the coding regions contribute to single amino acids repeats (SAARs) in the proteome. While SSRs in the coding region always result in amino acid repeats, a majority of SAARs arise due to a combination of various codons representing the same amino acid and not as a consequence of SSR events. Certain amino acids are abundant in repeat regions indicating a positive selection pressure behind the accumulation of SAARs. By analysing 22 proteomes including the human proteome, we explored the functional and structural relationship of amino acid repeats in an evolutionary context. Only ~15% of repeats are present in any known functional domain, while ~74% of repeats are present in the disordered regions, suggesting that SAARs add to the functionality of proteins by providing flexibility, stability and act as linker elements between domains. Comparison of SAAR containing proteins across species reveals that while shorter repeats are conserved among orthologs, proteins with longer repeats, >15 amino acids, are unique to the respective organism. Lysine repeats are well conserved among orthologs with respect to their length and number of occurrences in a protein. Other amino acids such as glutamic acid, proline, serine and alanine repeats are generally conserved among the orthologs with varying repeat lengths. These findings suggest that SAARs have accumulated in the proteome under positive selection pressure and that they provide flexibility for optimal folding of functional/structural domains of proteins. The insights gained from our observations can help in effective designing and engineering of proteins with novel features.
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad, 500007, India.
authors.forename: Amitha Sampath
authors.initials: AS
authors.lastname: Kumar
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad, 500007, India.
authors.forename: Divya Tej
authors.initials: DT
authors.lastname: Sowpati
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad, 500007, India.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D003062:Codon; D003198:Computer Simulation; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D007448:Invertebrates; D039122:Poly(A)-Binding Protein I / Q000235:genetics; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D020543:Proteome / Q000737:chemistry* / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid; D014714:Vertebrates
chemical_list: D003062:Codon; C576588:PABPN1 protein, human; D039122:Poly(A)-Binding Protein I; D011506:Proteins; D020543:Proteome