TIAMMAt: Leveraging biodiversity to revise protein domain models, evidence from innate immunity

Sequence annotation is fundamental for studying the evolution of protein families, particularly when working with non-model species. Given the rapid, ever-increasing number of species receiving high-quality genome sequencing, accurate domain modeling that is representative of species diversity is crucial for understanding protein family sequence evolution and their inferred function(s). Here, we describe a bioinformatic tool called TIAMMAt ( Taxon-Informed Adjustment of Markov Model Attributes) which revises domain profile hidden Markov models (HMMs) by incorporating homologous domain sequences from underrepresented and non-model species. Using innate immunity pathways as a case study, we show that revising profile HMM parameters to directly account for variation in homologs among underrepresented species provides valuable insight into the evolution of protein families. Following adjustment by TIAMMAt, domain profile HMMs exhibit changes in their per-site amino acid state emission probabilities and insertion/deletion probabilities while maintaining the overall structure of the consensus sequence. Our results show that domain revision can heavily impact evolutionary interpretations for some families (i.e., NLR’s NACHT domain), whereas impact on other domains (e.g., rel homology domain and interferon regulatory factor domains) is minimal due to high levels of sequence conservation across the sampled phylogenetic depth (i.e., Metazoa). Importantly, TIAMMAt revises target domain models to reflect homologous sequence variation using the taxonomic distribution under consideration by the user. TIAMMAt’s flexibility to revise any subset of the Pfam database using a user-defined taxonomic pool will make it a valuable tool for future protein evolution studies, particularly when incorporating (or focusing) on non-model species.

Mix and match: Patchwork domain evolution of the land plant-specific Ca2+-permeable mechanosensitive channel MCA

Multidomain proteins can have a complex evolutionary history that may involve de novo domain evolution, recruitment and / or recombination of existing domains and domain losses. Here, the domain evolution of the plant-specific Ca2+-permeable mechanosensitive channel protein, MID1-COMPLEMENTING ACTIVITY (MCA), was investigated. MCA, a multidomain protein, possesses a Ca2+-influx-MCAfunc domain and a PLAC8 domain. Profile Hidden Markov Models (HMMs) of domains were assessed in 25 viridiplantae proteomes. While PLAC8 was detected in plants, animals, and fungi, MCAfunc was found in streptophytes but not in chlorophytes. Full MCA proteins were only found in embryophytes. We identified the MCAfunc domain in all streptophytes including charophytes where it appeared in E3 ubiquitin ligase-like proteins. Our Maximum Likelihood (ML) analyses suggested that the MCAfunc domain evolved early in the history of streptophytes. The PLAC8 domain showed similarity to Plant Cadmium Resistance (PCR) genes, and the coupling of MCAfunc and PLAC8 seemed to represent a single evolutionary event. This combination is unique in MCA, and does not exist in other plant mechanosensitive channels. Within angiosperms, gene duplications increased the number of MCAs. Considering their role in mechanosensing in roots, MCA might be instrumental for the rise of land plants. This study provides a textbook example of de novo domain emergence, recombination, duplication, and losses, leading to the convergence of function of proteins in plants.

Enhancing the multi-dimensional assessment of quality of life: introducing the WHOQOL-Combi

Introduction We revisited the global concept of subjective quality of life (QoL) as assessed by the WHOQOL-BREF to investigate whether it could be elaborated into a conceptually more comprehensive instrument with good psychometric properties. Responding to a growing need for shorter QoL measures with broader social, spiritual and environmental contents, facets from WHOQOL international modules were examined for potential integration into the new WHOQOL-Combi. Method Adults over 65 years, diagnosed with one or more chronic diseases (n = 2833), completed 41 WHOQOL items during the CLASSIC survey; each item represented a WHOQOL facet. This pool of specific QoL facets contained 24 from the WHOQOL-BREF (excluding general items), and 17 from recent international WHOQOL short-form modules, selected for their generic properties. Rasch modelling reduced the final item pool when assessing the WHOQOL-Combi’s conceptual structure. Comparisons are made with the WHOQOL-BREF. Results Modelling confirmed the tenability of a 36-item solution scored as a five-domain profile, comprised of 24 WHOQOL-BREF facets and 12 new facets from modules. Social and psychological domains were strengthened by three facets, spiritual QoL by five, and physical QoL by one. The WHOQOL-Combi showed sound model fit, excellent internal consistency (α = .95), and scores discriminated between socio-demographic categories. Concurrent validity with the EQ-5D-5L was confirmed for physical and psychological domains. Performance was similar to the WHOQOL-BREF. Conclusion The WHOQOL-Combi offers a contemporary, comprehensive, integrated, multi-dimensional subjective QoL instrument with enhanced evaluations of social, spiritual, psychological and physical QoL. Acceptable to older people, future research should evaluate younger age groups and other cultures.

Pear IAA1 gene encoding an auxin-responsive Aux/IAA protein is involved in fruit development and response to salicylic acid

Shi, H., Wang, Y., Li, Z., Zhang, D., Zhang, Y., Xiang, D., Li, Y. and Zhang, Y. 2014. Pear IAA1 gene encoding an auxin-responsive Aux/IAA protein is involved in fruit development and response to salicylic acid. Can. J. Plant Sci. 94: 263–271. Auxin-responsive Aux/IAA proteins are rapidly auxin-induced, short-lived proteins that act as repressors for the auxin response factor (ARF)-activated gene expression. A gene encoding an Aux/IAA protein and designated PpIAA1 was isolated from pear (Pyrus pyrifolia). Using PCR amplification techniques, the genomic clone corresponding to PpIAA1 was isolated and shown to contain three introns with typical GT/AG boundaries defining the splice junctions. The deduced PpIAA1 protein contains the conserved features of indole-3-acetic acids (IAA): four Aux/IAA conserved domains, Aux/IAA family domain, Aux/IAA-ARF dimerization domain profile, and conserved nuclear localization signal (NLS) motifs. Phylogenetic analyses clearly demonstrated PpIAA1 has the highest homology with grape VvIAA. PpIAA1 was preferentially expressed in fruit, and moderate expression was found in anthers. Relatively low expression signal was detected in other tissues including shoots, leaves, and petals. Moreover, expression of PpIAA1 was developmentally regulated in fruit. Further study demonstrated that PpIAA1 expression in pear fruit was remarkably regulated by salicylic acid and IAA. The data suggest that PpIAA1 might be involved in the interplay between IAA and salicylic acid signaling pathway during the fruit development of pear.