Divergent evolution and purifying selection of the Type 2 diabetes gene sequences in Drosophila : a phylogenomic study
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ORIGINAL PAPER
Divergent evolution and purifying selection of the Type 2 diabetes gene sequences in Drosophila: a phylogenomic study Manoj Kumar Gupta1 · Ramakrishna Vadde1 Received: 30 November 2019 / Accepted: 12 August 2020 © Springer Nature Switzerland AG 2020
Abstract The recently developed phylogenomic approach provides a unique way to identify disease risk or protective allele in any organism. While risk alleles evolve mostly under purifying selection, protective alleles are evolving either under balancing or positive selection. Owing to insufficient information, authors employed the phylogenomic approach to detect the nature of selection acting on type 2 diabetes (T2D) genes in Drosophila genus using various models of CODEML utility of PAML. The obtained result revealed that T2D gene sequences are evolving under purifying selection. However, only a few sites in membrane proteins encoded via CG8051, ZnT35C, and kar, are significantly evolving under positive selection under specific scenarios, which might be because of positive or adaptive evolution in response to changing niche, diet or other factors. In the near future, this information will be highly useful in the field of evolutionary medicine and the drug discovery process. Keywords Type 2 diabetes · Natural selection · Drosophila · Phylogenomics
Introduction Diabetes mellitus (DM) is a polygenic disease. Clinically it is characterized by hyperglycemia, polyuria (frequent urination), polyphagia (hunger), polydipsia (thirst), and loss of weight. DM is mainly of two types, namely, type 1 diabetes (T1D) & type 2 diabetes (T2D). T1D is clinically characterized via autoimmune destruction of insulin-producing pancreatic β cells; if not treated early results in absolute insulin deficiency. T2D is characterized via resistance towards the action of insulin as well as an incapability to produce adequate levels of insulin for overcoming ’insulin resistance’ (Walker and Colledge 2013). While T1D is an autoimmune disease, obesity is a major risk factor for causing T2D along with various other genetics as well as environmental factors (Thirlaway and Davies 2001; Baynest 2015; Skyler et al. 2017). As T2D is a complex disorder, there are Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10709-020-00101-7) contains supplementary material, which is available to authorized users. * Ramakrishna Vadde [email protected]; [email protected] 1
Department of Biotechnology & Bioinformatics, Yogi Vemana University, Kadapa, Andhra Pradesh 516005, India
still numerous debates on the actual cause, mechanism, and treatment associated with T2D. Thus, interest to understand the mechanism as well as to find a possible therapeutic for T2D with minimum side effects has revolutionized the field of diabetic research. Researchers are implementing several new technologies, like nanotechnology, statins, and gene therapy, for the treatment of T2D. Nevertheless, these new technologies, along with the traditional medici
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