Elevated Evolutionary Rate in Genes with Homopolymeric Amino Acid Repeats Constituting Nondisordered Structure

Abstract

Homopolymeric amino acid repeats are tandem repeats of single amino acids. About 650 genes are known to have repeats of this kind comprising seven residues or more in the human genome. According to the evolutionary conservativeness, we classified the repeats into three categories: those whose length is conserved among mammals (CM), those whose length differs among nonprimate mammals but is conserved among primates (CP), and those whose length differs among primates (VP). The frequency of each repeat, especially Ala, Leu, Pro, and Glu repeats, varies greatly in each category. The 3D structure of homopolymeric amino acid repeats is considered to be intrinsically disordered. As expected, a large proportion of the repeats had a disordered structure, and nearly half of the repeats were predicted as completely disordered. However, a number of the repeats predicted to have nondisordered structure: 13% and 25% of the repeats for categories CM and VP, respectively. Comparison of the substitution rates showed a higher Ka/Ks ratio for the genes with not disordered repeats than the genes with disordered repeats. These results indicate that amino acid substitution rates have been elevated in the genes with nondisordered repeats.

Mammalian-Specific Sequences in Pou3f2 Contribute to Maternal Behavior

“…Our discovery suggests that pup retrieval, an essential mammalian maternal behavior, is established via enhanced dopaminergic and serotonergic neurotransmission in the brain by homopolymeric amino acid repeats acquired in the mammalian POU3F2. Hundreds of mammalian genes have homopolymeric amino acid repeats, ∼80% of which are evolutionarily well conserved in length (Mularoni et al 2006; Gojobori and Ueda 2011). The majority of genes having repeats play important roles in transcription/translation and signaling processes (Faux et al 2005), but very little is known about the evolutionary implications of repeat acquisition.…”

Association of polyalanine and polyglutamine coiled coils mediates expansion disease-related protein aggregation and dysfunction

“…Together with the in vitro experiments, these observations indicate that polyA CCs have a greater stability as compared with polyQ CCs of the same length. There is evidence for the evolutionary selection of shorter and less polymorphic polyA repeats with respect to polyQ repeats (68). At the same time, the disease threshold for polyA expansions is lower than that for polyQ expansions (2,69).…”

Polyglutamine Repeats Are Associated to Specific Sequence Biases That Are Conserved among Eukaryotes

“…Remarkably, these robust biases are not the consequence of a conservative evolution from common protein ancestors (Figures 7 and S2). Indeed, if many of the human polyQ-containing proteins orthologues are conserved amongst eukaryotes, polyQ presence and length within a given protein are rarely conserved [24], [27], [29], [35]–[37], [43], [44]. Huntingtin for example is conserved in all deuterostomia; however, only vertebrate's huntingtin contains polyQs and they are of different lengths [45].…”