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Lineage-specific protein repeat expansions and contractions reveal malleable regions of immune genes

Genes & Immunity volume 23, pages 218–234 (2022)Cite this article

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Abstract

Functional diversification, a higher evolutionary rate, and intense positive selection help a limited number of immune genes interact with many pathogens. Repeats in protein-coding regions are a well-known source of functional diversification, adaptive variation, and evolutionary novelty in a short time. Repeats play a crucial role in biochemical functions like functional diversification of transcription regulation, protein kinases, cell adhesion, signaling pathways, morphogenesis, DNA repair, recombination, and RNA processing. Repeat length variation can change the associated protein’s interaction, efficacy, and overall protein network. Repeats have an intrinsic unstable nature and can potentially evolve rapidly and expedite the acquisition of complex phenotypic traits and functions. Because of their ability to generate rapid, adaptive variations over short evolutionary distances, repeats are considered “tuning knobs.” Repeat length variation in specific genes, like RUNX2 and ALX4, is associated with morphological and physiological changes across vertebrates. Here we study repeat length variation as a potent source of species-specific immune diversification across several clades of tetrapods. Moreover, we provide a clade-wise comprehensive list of immune genes with repeat types for future studies of morphological/evolutionary changes within species groups. We observe significant repeat length variation of FASLG and C1QC in Rodentia and Primates’ contrasting species groups, respectively.

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Fig. 1: Repeat-containing immune genes specialize in specific functions.
Fig. 2: Repeats are preferred in specific GC% range genes.
Fig. 3: Genes may contain multiple repeats.
Fig. 4: Repeats show length volatility across species and clades.
Fig. 5: Global patterns of repeat-length variability across clades.
Fig. 6: PolyP repeat shows lineage-specific length variability in the FASLG gene in the Rodentia clade.

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Data availability

All data associated with this study are available in the Supplementary Materials, and data and scripts used for analysis are provided in an easy-to-browse format: https://github.com/ceglablokdeep/Immune_genes_repeats. A copy of the data has been uploaded on Mendeley datasets with https://doi.org/10.17632/8zxtjh8fjs.1.

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Acknowledgements

We thank the Ministry of Human Resource Development for fellowship to LT and SS.

Funding

Computational analyses were done on the Har Gobind Khorana Computational Biology cluster established and maintained by combining funds from IISER Bhopal under Grant # INST/BIO/2017/019, IYBA 2018 from the Department of Biotechnology (Grant no. BT/11/IYBA/2018/03), and ECRA from Science and Engineering Research Board (Grant no. ECR/2017/001430).

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  1. Department of Biological Sciences, Computational Evolutionary Genomics Lab, IISER Bhopal, Bhauri, Madhya Pradesh, India

    Lokdeep Teekas, Sandhya Sharma & Nagarjun Vijay

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LT and SS wrote the manuscript with NV. LT and SS analyzed the data and generated the results. All authors reviewed the manuscript.

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Teekas, L., Sharma, S. & Vijay, N. Lineage-specific protein repeat expansions and contractions reveal malleable regions of immune genes. Genes Immun 23, 218–234 (2022). https://doi.org/10.1038/s41435-022-00186-4

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