Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations.
ABSTRACT: The transition from land to water in whales and dolphins (cetaceans) was accompanied by remarkable adaptations. To reveal genomic changes that occurred during this transition, we screened for protein-coding genes that were inactivated in the ancestral cetacean lineage. We found 85 gene losses. Some of these were likely beneficial for cetaceans, for example, by reducing the risk of thrombus formation during diving (F12 and KLKB1), erroneous DNA damage repair (POLM), and oxidative stress-induced lung inflammation (MAP3K19). Additional gene losses may reflect other diving-related adaptations, such as enhanced vasoconstriction during the diving response (mediated by SLC6A18) and altered pulmonary surfactant composition (SEC14L3), while loss of SLC4A9 relates to a reduced need for saliva. Last, loss of melatonin synthesis and receptor genes (AANAT, ASMT, and MTNR1A/B) may have been a precondition for adopting unihemispheric sleep. Our findings suggest that some genes lost in ancestral cetaceans were likely involved in adapting to a fully aquatic lifestyle.
Project description:Recent studies have reported multiple cases of molecular adaptation in cetaceans related to their aquatic abilities. However, none of these has included the hippopotamus, precluding an understanding of whether molecular adaptations in cetaceans occurred before or after they split from their semi-aquatic sister taxa. Here, we obtained new transcriptomes from the hippopotamus and humpback whale, and analysed these together with available data from eight other cetaceans. We identified more than 11?000 orthologous genes and compiled a genome-wide dataset of 6845 coding DNA sequences among 23 mammals, to our knowledge the largest phylogenomic dataset to date for cetaceans. We found positive selection in nine genes on the branch leading to the common ancestor of hippopotamus and whales, and 461 genes in cetaceans compared to 64 in hippopotamus. Functional annotation revealed adaptations in diverse processes, including lipid metabolism, hypoxia, muscle and brain function. By combining these findings with data on protein-protein interactions, we found evidence suggesting clustering among gene products relating to nervous and muscular systems in cetaceans. We found little support for shared ancestral adaptations in the two taxa; most molecular adaptations in extant cetaceans occurred after their split with hippopotamids.
Project description:Cetaceans have long been considered capable of limiting diving-induced nitrogen absorption and subsequent decompression sickness through a series of behavioral, anatomical, and physiological adaptations. Recent studies however suggest that in some situations these adaptive mechanisms might be overcome, resulting in lethal and sublethal injuries. Perhaps most relevant to this discussion is the finding of intravascular gas and fat emboli in mass-stranded beaked whales. Although the source of the gas emboli has as yet to been ascertained, preliminary findings suggest nitrogen is the primary component. Since nitrogen gas embolus formation in divers is linked to nitrogen saturation, it seems premature to dismiss similar pathogenic mechanisms in breath-hold diving cetaceans. Due to the various anatomical adaptations in cetacean lungs, the pulmonary system is thought of as an unlikely site of significant nitrogen absorption. The accessory sinus system on the ventral head of odontocete cetaceans contains a sizeable volume of air that is exposed to the changing hydrostatic pressures during a dive, and is intimately associated with vasculature potentially capable of absorbing nitrogen through its walls. The source of the fat emboli has also remained elusive. Most mammalian fat deposits are considered poorly vascularized and therefore unlikely sites of intravascular introduction of lipid, although cetacean blubber may not be as poorly vascularized as previously thought. We present new data on the vasculature of air sinuses and acoustic fat bodies in the head of bottlenose dolphins and compare it to published accounts. We show that the mandibular fat bodies and accessory sinus system are associated with extensive venous plexuses and suggest potential physiological and pathological implications.
Project description:Hypoxia was a major challenge faced by cetaceans during the course of secondary aquatic adaptation. Although physiological traits of hypoxia tolerance in cetaceans have been well characterized, the underlying molecular mechanisms remain unknown. We investigated the sequences of 17 hypoxia-tolerance-related genes in representative cetaceans to provide a comprehensive insight into the genetic basis of hypoxia tolerance in these animals. Genes involved in carrying and transporting oxygen in the blood and muscle (hemoglobin-? and ?, myoglobin), and genes involved in the regulation of vasoconstriction (endothelin-1, -2, and -3; endothelin receptor type A and B; adrenergic receptor ?-1D; and arginine vasopressin) appear to have undergone adaptive evolution, evidence for positive selection on their particular sites, and radical physiochemical property changes of selected condons. Interestingly, "long-diving" cetaceans had relatively higher ? (dN/dS) values than "short-diving" cetaceans for the hemoglobin ? gene, indicating divergent selective pressure presented in cetacean lineages with different diving abilities. Additionally, parallel positive selection or amino acid changes (ADRA1D: P50A, A53G,AVPR1B: I/V270T) among animals exposed to different hypoxia habitats reflect functional convergence or similar genetic mechanisms of hypoxia tolerance. In summary, positive selection, divergent selective pressures, and parallel evolution at the molecular level provided some new insights into the genetic adaptation of hypoxia tolerance.
Project description:Cetaceans are a group of marine mammals whose ancestors were adaptated for life on land. Life in an aquatic environment poses many challenges for air-breathing mammals. Diving marine mammals have adapted to rapid reoxygenation and reactive oxygen species (ROS)-mediated reperfusion injury. Here, we considered the evolution of the glutathione transferase (GST) gene family which has important roles in the detoxification of endogenously-derived ROS and environmental pollutants. We characterized the cytosolic GST gene family in 21 mammalian species; cetaceans, sirenians, pinnipeds, and their terrestrial relatives. All seven GST classes were identified, showing that GSTs are ubiquitous in mammals. Some GST genes are the product of lineage-specific duplications and losses, in line with a birth-and-death evolutionary model. We detected sites with signatures of positive selection that possibly influence GST structure and function, suggesting that adaptive evolution of GST genes is important for defending mammals from various types of noxious environmental compounds. We also found evidence for loss of alpha and mu GST subclass genes in cetacean lineages. Notably, cetaceans have retained a homolog of at least one of the genes GSTA1, GSTA4, and GSTM1; GSTs that are present in both the cytosol and mitochondria. The observed variation in number and selection pressure on GST genes suggest that the gene family structure is dynamic within cetaceans.
Project description:BACKGROUND:The transition from land to sea by the ancestor of cetaceans approximately 50 million years ago was an incredible evolutionary event that led to a series of morphological, physiological, and behavioral adaptations. During this transition, bone microstructure evolved from the typical terrestrial form to the specialized structure found in modern cetaceans. While the bone microstructure of mammals has been documented before, investigations of its genetic basis lag behind. The increasing number of cetaceans with whole-genome sequences available may shed light on the mechanism underlying bone microstructure evolution as a result of land to water transitions. RESULTS:Cetacean bone microstructure is consistent with their diverse ecological behaviors. Molecular evolution was assessed by correlating bone microstructure and gene substitution rates in terrestrial and aquatic species, and by detecting genes under positive selection along ancestral branches of cetaceans. We found that: 1) Genes involved in osteoclast function are under accelerated evolution in cetaceans, suggestive of important roles in bone remodeling during the adaptation to an aquatic environment; 2) Genes in the Wnt pathway critical for bone development and homeostasis show evidence of divergent evolution in cetaceans; 3) Several genes encoding bone collagens are under selective pressure in cetaceans. CONCLUSIONS:Our results suggest that evolutionary pressures have shaped the bone microstructure of cetaceans, to facilitate life in diverse aquatic environments.
Project description:Extant cetaceans, such as sperm whale, acquired the great ability to dive into the ocean depths during the evolution from their terrestrial ancestor that lived about 50 million years ago. Myoglobin (Mb) is highly concentrated in the myocytes of diving animals, in comparison with those of land animals, and is thought to play a crucial role in their adaptation as the molecular aqualung. Here, we resurrected ancestral whale Mbs, which are from the common ancestor between toothed and baleen whales (Basilosaurus), and from a further common quadrupedal ancestor between whale and hippopotamus (Pakicetus). The experimental and theoretical analyses demonstrated that whale Mb adopted two distinguished strategies to increase the protein concentration in vivo along the evolutionary history of deep sea adaptation; gaining precipitant tolerance in the early phase of the evolution, and increase of folding stability in the late phase.
Project description:Different marine mammal species exhibit a wide range of diving behaviour based on their breath-hold diving capabilities. They are classically categorized as long duration, deep-diving and short duration, shallow-diving species. These abilities are likely to be related to the muscle characteristics of each species. Despite the increasing number of publications on muscle profile in different cetacean species, very little information is currently available concerning the characteristics of other muscle components in these species. In this study, we examined skeletal muscle fiber type, fiber size (cross sectional area and lesser diameter), intramuscular substrates, and perimysium-related structures, by retrospective study in 146 stranded cetaceans involving 15 different species. Additionally, we investigated diving profile-specific histological features. Our results suggest that deep diving species have higher amount of intramyocyte lipid droplets, and evidence higher percentage of intramuscular adipose tissue, and larger fibre sizes in this group of animals.
Project description:Foraging disruption caused by human activities is emerging as a key issue in cetacean conservation because it can affect nutrient levels and the amount of energy available to individuals to invest into reproduction. Our ability to predict how anthropogenic stressors affect these ecological processes and ultimately population trajectory depends crucially on our understanding of the complex physiological mechanisms that detect nutrient availability and regulate energy metabolism, foraging behavior and life-history decisions. These physiological mechanisms are likely to differ considerably from terrestrial mammalian model systems. Here, we examine nucleotide substitution rates in cetacean and other artiodactyl genomes to identify signatures of selection in genes associated with nutrient sensing pathways. We also estimated the likely physiological consequences of adaptive amino acid substitutions for pathway functions. Our results highlight that genes involved in the insulin, mTOR and NF-?B pathways are subject to significant positive selection in cetaceans compared to terrestrial artiodactyla. These genes may have been positively selected to enable cetaceans to adapt to a glucose-poor diet, to overcome deleterious effects caused by hypoxia during diving (e.g. oxidative stress and inflammation) and to modify fat-depot signaling functions in a manner different to terrestrial mammals. We thus show that adaptation in cetaceans to an aquatic lifestyle significantly affected functions in nutrient sensing pathways. The use of fat stores as a condition index in cetaceans may be confounded by the multiple and critical roles fat has in regulating cetacean metabolism, foraging behavior and diving physiology.
Project description:This research was conducted to estimate the effects of Persicaria odorata leaf meal (POLM) on haematological indices, serum biochemical attributes, and internal organs parameters, including histomorphological features of the liver, in broiler chickens. A total of 120 one-day-old male broiler chicks (Cobb-500) were randomly allocated into four experimental groups. The dietary treatments were basal diet (BD), which served as the control (C), along with BD + 2 g/kg POLM (Po2), BD + 4 g/kg POLM (Po4), BD + 8 g/kg POLM (Po8), which were the supplemented groups. The body weight gain (BWG) showed a linear increase and feed conversion ratio (FCR) showed a linear decrease with increasing POLM dosage at day 42 (p ? 0.05) and for the overall growth performance period (p ? 0.01). On day 21 and day 42, the values of red blood cells (RBCs), white blood cells (WBCs), haemoglobin (Hb), and packed cell volume (PCV) showed linear increases (p ?0.05) as the dosage of POLM increased in the diet. On day 21, dietary supplementation of POLM linearly decreased (p ? 0.05) the serum activity of alkaline phosphatase (ALP), aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), and serum levels of urea and creatinine. On the other hand, serum levels of total protein (TP), albumin, and globulin showed a linear increase (p ? 0.05) as the POLM dosage increased. On day 42, the serum activity of AST and ALT and serum levels of glucose, cholesterol, triglycerides, urea, and creatinine showed linear decreases (p ? 0.05) with increased levels of POLM in the diet. However, POLM supplementation linearly increased (p ? 0.05) the serum levels of TP and globulin. Dietary inclusion of POLM did not influence the organ parameters and showed no adverse effects on the liver histomorphology. In conclusion, supplementation of POLM increased the growth performance, improving haematological indices and serum biochemistry profiles of broiler chickens without any deleterious effects on the liver histomorphology. The results of the present study provide evidence that POLM can be safely used at a dose rate of 8 g/kg of feed as an alternative to conventional antimicrobial growth promoters (AGPs).
Project description:Identifying additional mitogen-activated protein kinase (MAPK) pathway regulators is invaluable in aiding our understanding of the complex signaling networks that regulate cellular processes, including cell proliferation and survival. Here, using in vitro kinase assays and by expressing WT or kinase-dead MAPK kinase kinase 19 (MAP3K19) in the HEK293T cell line and assessing activation of the extracellular signal-regulated kinase (ERK) and JUN N-terminal kinase (JNK) signaling pathways, we defined MAP3K19 as a novel regulator of MAPK signaling. We also observed that overexpression of WT MAP3K19 activates both the ERK and JNK pathways in a panel of cancer cell lines. Furthermore, MAP3K19 sustained ERK pathway activation in the presence of inhibitors targeting the RAF proto-oncogene Ser/Thr protein kinase (RAF) and MAPK/ERK kinase, indicating that MAP3K19 activates ERK via a RAF-independent mechanism. Findings from in vitro and in-cell kinase assays demonstrate that MAP3K19 is a kinase that directly phosphorylates both MAPK/ERK kinase (MEK) and MAPK kinase 7 (MKK7). Results from an short-hairpin RNA screen indicated that MAP3K19 is essential for maintaining survival in KRAS-mutant cancers; therefore, we depleted or inhibited MAP3K19 in KRAS-mutant cancer cell lines and observed that this reduces viability and decreases ERK and JNK pathway activation. In summary, our results reveal that MAP3K19 directly activates the ERK and JNK cascades and highlight a role for this kinase in maintaining survival of KRAS-mutant lung cancer cells.