Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of primate-ethanol interactions. The evolving catalytic properties of these resurrected enzymes show that our ape ancestors gained a digestive dehydrogenase enzyme capable of metabolizing ethanol near the time that they began using the forest floor, about 10 million y ago. The ADH4 enzyme in our more ancient and arboreal ancestors did not efficiently oxidize ethanol. This change suggests that exposure to dietary sources of ethanol increased in hominids during the early stages of our adaptation to a terrestrial lifestyle. Because fruit collected from the forest floor is expected to contain higher concentrations of fermenting yeast and ethanol than similar fruits hanging on trees, this transition may also be the first time our ancestors were exposed to (and adapted to) substantial amounts of dietary ethanol.experimental paleogenetics | alcohol dehydrogenase | ethanol | primates | evolution

BackgroundGene duplication is a source of molecular innovation throughout evolution. However, even with massive amounts of genome sequence data, correlating gene duplication with speciation and other events in natural history can be difficult. This is especially true in its most interesting cases, where rapid and multiple duplications are likely to reflect adaptation to rapidly changing environments and life styles. This may be so for Class I of alcohol dehydrogenases (ADH1s), where multiple duplications occurred in primate lineages in Old and New World monkeys (OWMs and NWMs) and hominoids.Methodology/Principal FindingsTo build a preferred model for the natural history of ADH1s, we determined the sequences of nine new ADH1 genes, finding for the first time multiple paralogs in various prosimians (lemurs, strepsirhines). Database mining then identified novel ADH1 paralogs in both macaque (an OWM) and marmoset (a NWM). These were used with the previously identified human paralogs to resolve controversies relating to dates of duplication and gene conversion in the ADH1 family. Central to these controversies are differences in the topologies of trees generated from exonic (coding) sequences and intronic sequences.Conclusions/SignificanceWe provide evidence that gene conversions are the primary source of difference, using molecular clock dating of duplications and analyses of microinsertions and deletions (micro-indels). The tree topology inferred from intron sequences appear to more correctly represent the natural history of ADH1s, with the ADH1 paralogs in platyrrhines (NWMs) and catarrhines (OWMs and hominoids) having arisen by duplications shortly predating the divergence of OWMs and NWMs. We also conclude that paralogs in lemurs arose independently. Finally, we identify errors in database interpretation as the source of controversies concerning gene conversion. These analyses provide a model for the natural history of ADH1s that posits four ADH1 paralogs in the ancestor of Catarrhine and Platyrrhine primates, followed by the loss of an ADH1 paralog in the human lineage.

Заключение: для выявления больных бронхиальной астмой, у которых имеется повышенный риск развития гипертонической болезни, может быть использована оценка полиморфизма NOS3 786C/T.Ключевые слова: бронхиальная астма, генетический полиморфизм, синтаза оксида азота, гипертоническая болезнь. ______________________________________________________________________________ Последние годы всё большее внима-ние исследователей привлекает проблема коморбидности. Изучение коморбидной патологии способствует более ясному по-ниманию механизма развития болезней и разработке патогенетически обоснованной

Present literature review highlights the current views on the role of genetic factors in the development of bronchial asthma and hypertension, indicates their role in the formation of comorbid pathology, draws attention to the role of nitric oxide and nitric oxide synthase genes in the pathogenesis. In recent years there has been increasing interest of researchers to the problem of comorbidity, in particular to a combination of asthma and hypertension. Genetic factors play a great role in pathogenesis of these diseases. Among genes that play role in development of asthma there are genes encoding antigen recognition factors and humoral immune response factors, genes encoding mediators of inflammation, chemokines and intercellular adhesion molecules, genes of receptors performing fixation of external ligand molecules on the target cell, genes of intracellular signaling molecules and transcription factors and a number of other genes. The pathogenesis of essential hypertension is associated with the genes of renin-angiotensin-aldosterone system and genes regulating endothelial status. The link between asthma and hypertension is nitric oxide, which is involved in many physiological processes, in particular, regulates vascular and respiratory tone. Polymorphism of nitric oxide synthases genes is able to violate its production in the organism and thus lead to the development of bronchial asthma and hypertension. Polymorphisms Glu298Asp, eNOS4a/b, and 786C/T of NOS3 gene are associated with development of hypertension. Polymorphisms of this gene had been studied in patients with bronchial asthma, and they have demonstrated their influence on the level of nitric oxide in patients. Thus, the NOS gene polymorphisms may participate in the formation of comorbidity of bronchial asthma and hypertension.

Aim. To evaluate the clinical and pathogenetic value of nitric oxide metabolites measurement in the blood of patients with bronchial asthma and essential hypertension. Methods. The study included 91 patients. Three groups were identified: patients with bronchial asthma (30 patients, group 1), patients with bronchial asthma in combination with essential hypertension (31 patients, group 2), and patients with essential hypertension (30 patients, group 3). Measurement of the level of total nitric oxide metabolites in patients’ blood was performed with the use of spectrophotometric method in light spectrum based on Griess reaction. Results. The median level of nitric oxide metabolites had the highest value in the blood of patients with bronchial asthma and accounted for 75.6 [70.4; 80.8] umol/L. Level of nitric oxide metabolites in the blood of patients with bronchial asthma in combination with essential hypertension and patients with essential hypertension was lower, accounting for 72.4 [66.2; 81.2] and 60.0 [54.6; 62.7] umol/L respectively (p