Using Paleogenomics to Study the Evolution of Gene Families: Origin and Duplication History of the Relaxin Family Hormones and Their Receptors

Recent progress in the analysis of whole genome sequencing data has resulted in the emergence of paleogenomics, a field devoted to the reconstruction of ancestral genomes. Ancestral karyotype reconstructions have been used primarily to illustrate the dynamic nature of genome evolution. In this paper, we demonstrate how they can also be used to study individual gene families by examining the evolutionary history of relaxin hormones (RLN/INSL) and relaxin family peptide receptors (RXFP). Relaxin family hormones are members of the insulin superfamily, and are implicated in the regulation of a variety of primarily reproductive and neuroendocrine processes. Their receptors are G-protein coupled receptors (GPCR's) and include members of two distinct evolutionary groups, an unusual characteristic. Although several studies have tried to elucidate the origins of the relaxin peptide family, the evolutionary origin of their receptors and the mechanisms driving the diversification of the RLN/INSL-RXFP signaling systems in non-placental vertebrates has remained elusive. Here we show that the numerous vertebrate RLN/INSL and RXFP genes are products of an ancestral receptor-ligand system that originally consisted of three genes, two of which apparently trace their origins to invertebrates. Subsequently, diversification of the system was driven primarily by whole genome duplications (WGD, 2R and 3R) followed by almost complete retention of the ligand duplicates in most vertebrates but massive loss of receptor genes in tetrapods. Interestingly, the majority of 3R duplicates retained in teleosts are potentially involved in neuroendocrine regulation. Furthermore, we infer that the ancestral AncRxfp3/4 receptor may have been syntenically linked to the AncRln-like ligand in the pre-2R genome, and show that syntenic linkages among ligands and receptors have changed dynamically in different lineages. This study ultimately shows the broad utility, with some caveats, of incorporating paleogenomics data into understanding the evolution of gene families

Pitavastatin – A New Inhibitor of the HMG-CoA Reductase: Peculiarities of Clinical Pharmacology and Perspectives of Its Usage in Treatment of Cardiovascular Diseases.

Cardiovascular mortality makes up 66.3 % of the total mortality in Ukraine. Myocardial infarction, stroke, atherosclerosis of peripheral arteries are the diseases caused by atherosclerosis and are prevalent in the mortality structure. One of the most effective means of successful prevention of cardiovascular disease are drugs that reduce the content of atherogenic lipids in the blood. Statins are the first line drugs for the treatment of patients with dyslipidemia and atherosclerosis in accordance with national and International guidelines. The article presents the features of the pharmacokinetics and pharmacodynamics, results of clinical trials and data on the efficacy and safety of a new inhibitor of the HMG-CoA reductase – pitavastatin (Livazo © (Recordati, Italy). Data from several multicenter randomized studies indicate that pitavastatin significantly reduces the level of cholesterol low-density lipoproteins and triglycerides, significantly increases the level of cholesterol high-density lipoproteins after 12 weeks of observation, and contributes to a significant regression of atherosclerotic plaques. It was shown that pitavastatin has a high level of safety and is well tolerated regardless of patients' age and racial origin. Pitavastatin is a new effective inhibitor of HMG -CoA reductase, which has been successfully used in many countries for the dyslipidemia treatment in patients with cardiovascular disease, diabetes, kidney diseases and other comorbid conditions