(Micro)evolutionary changes and the evolutionary potential of bird migration

Seasonal migration is the yearly long-distance movement of individuals between their breeding and wintering grounds. Individuals from nearly every animal group exhibit this behavior, but probably the most iconic migration is carried out by birds, from the classic V-shape formation of geese on migration to the amazing nonstop long-distance flights undertaken by Arctic Terns Sterna paradisaea. In this chapter, we discuss how seasonal migration has shaped the field of evolution. First, this behavior is known to turn on and off quite rapidly, but controversy remains concerning where this behavior first evolved geographically and whether the ancestral state was sedentary or migratory (Fig. 7.1d, e). We review recent work using new analytical techniques to provide insight into this topic. Second, it is widely accepted that there is a large genetic basis to this trait, especially in groups like songbirds that migrate alone and at night precluding any opportunity for learning. Key hypotheses on this topic include shared genetic variation used by different populations to migrate and only few genes being involved in its control. We summarize recent work using new techniques for both phenotype and genotype characterization to evaluate and challenge these hypotheses. Finally, one topic that has received less attention is the role these differences in migratory phenotype could play in the process of speciation. Specifically, many populations breed next to one another but take drastically different routes on migration (Fig. 7.2). This difference could play an important role in reducing gene flow between populations, but our inability to track most birds on migration has so far precluded evaluations of this hypothesis. The advent of new tracking techniques means we can track many more birds with increasing accuracy on migration, and this work has provided important insight into migration's role in speciation that we will review here

Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation

Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. / Methods: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. / Results: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. / Conclusions: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF

The application of cortical layer markers in the evaluation of cortical dysplasias in epilepsy

The diagnostic criteria for focal cortical dysplasia type I (FCD I) remain to be well and consistently defined. Cortical layer-specific markers (CLM) provide a potential tool for the objective assessment of any dyslamination. We studied expression patterns of recognised CLM using immunohistochemistry for N200, ER81, Otx1, Map1b (subsets of V/VI projection neurones), Pax6, Tbr1, Tbr2 (differentially expressed in cortical neurones from intermediate progenitor cells), Cux 1 (outer cortical layers) and MASH1 (ventricular zone progenitors). Dysplasia subtypes included FCD I and II, dysplasias adjacent to hippocampal sclerosis (HS) or dysembryoplastic neuroepithelial tumours (DNTs); all were compared to neonatal and adult controls. Laminar expression patterns in normal cortex were observed with Tbr1, Map1b, N200 and Otx1. FCDI cases in younger patients were characterised by abnormal expression in layer II for Tbr1 and Otx1. FCDII showed distinct labelling of balloon cells (Pax6, ER81 and Otx1) and dysmorphic neurones (Tbr 1, N200 and Map1b) supporting origins from radial glia and intermediate progenitor cells, respectively. In temporal lobe sclerosis cases with dysplasia adjacent to HS, Tbr1 and Map1b highlighted abnormal orientation of neurones in layer II. Dyslamination was not confirmed in the perilesional cortex of DNT with CLM. Finally, immature cell types (Otx1, Pax6 and Tbr2) were noted in varied pathologies. One possibility is activation of progenitor cell populations which could contribute to the pathophysiology of these lesions

Complex evolutionary history of the Mexican stoneroller Campostoma ornatum Girard, 1856 (Actinopterygii: Cyprinidae)

<p>Abstract</p> <p>Background</p> <p>Studies of the phylogeography of Mexican species are steadily revealing genetic patterns shared by different species, which will help to unravel the complex biogeographic history of the region. <it>Campostoma ornatum </it>is a freshwater fish endemic to montane and semiarid regions in northwest Mexico and southern Arizona. Its wide range of distribution and the previously observed morphological differentiation between populations in different watersheds make this species a useful model to investigate the biogeographic role of the Sierra Madre Occidental and to disentangle the actions of Pliocene tecto-volcanic processes <it>vs </it>Quaternary climatic change. Our phylogeographic study was based on DNA sequences from one mitochondrial gene (<it>cytb</it>, 1110 bp, n = 285) and two nuclear gene regions (S7 and RAG1, 1822 bp in total, n = 56 and 43, respectively) obtained from 18 to 29 localities, in addition to a morphological survey covering the entire distribution area. Such a dataset allowed us to assess whether any of the populations/lineages sampled deserve to be categorised as an evolutionarily significant unit.</p> <p>Results</p> <p>We found two morphologically and genetically well-differentiated groups within <it>C. ornatum</it>. One is located in the northern river drainages (Yaqui, Mayo, Fuerte, Sonora, Casas Grandes, Santa Clara and Conchos) and another one is found in the southern drainages (Nazas, Aguanaval and Piaxtla). The split between these two lineages took place about 3.9 Mya (CI = 2.1-5.9). Within the northern lineage, there was strong and significant inter-basin genetic differentiation and also several secondary dispersal episodes whit gene homogenization between drainages. Interestingly, three divergent mitochondrial lineages were found in sympatry in two northern localities from the Yaqui river basin.</p> <p>Conclusions</p> <p>Our results indicate that there was isolation between the northern and southern phylogroups since the Pliocene, which was related to the formation of the ancient Nazas River paleosystem, where the southern group originated. Within groups, a complex reticulate biogeographic history for <it>C. ornatum </it>populations emerges, following the taxon pulse theory and mainly related with Pliocene tecto-volcanic processes. In the northern group, several events of vicariance promoted by river or drainage isolation episodes were found, but within both groups, the phylogeographic patterns suggest the occurrence of several events of river capture and fauna interchange. The Yaqui River supports the most diverse populations of <it>C. ornatum</it>, with several events of dispersal and isolation within the basin. Based on our genetic results, we defined three ESUs within <it>C. ornatum </it>as a first attempt to promote the conservation of the evolutionary processes determining the genetic diversity of this species. They will likely be revealed as a valuable tool for freshwater conservation policies in northwest Mexico, where many environmental problems concerning the use of water have rapidly arisen in recent decades.</p

Targeted plant improvement through genome editing: from laboratory to field

This review illustrates how far we have come since the emergence of GE technologies and how they could be applied to obtain superior and sustainable crop production. The main challenges of today's agriculture are maintaining and raising productivity, reducing its negative impact on the environment, and adapting to climate change. Efficient plant breeding can generate elite varieties that will rapidly replace obsolete ones and address ongoing challenges in an efficient and sustainable manner. Site-specific genome editing in plants is a rapidly evolving field with tangible results. The technology is equipped with a powerful toolbox of molecular scissors to cut DNA at a pre-determined site with different efficiencies for designing an approach that best suits the objectives of each plant breeding strategy. Genome editing (GE) not only revolutionizes plant biology, but provides the means to solve challenges related to plant architecture, food security, nutrient content, adaptation to the environment, resistance to diseases and production of plant-based materials. This review illustrates how far we have come since the emergence of these technologies and how these technologies could be applied to obtain superior, safe and sustainable crop production. Synergies of genome editing with other technological platforms that are gaining significance in plants lead to an exciting new, post-genomic era for plant research and production. In previous months, we have seen what global changes might arise from one new virus, reminding us of what drastic effects such events could have on food production. This demonstrates how important science, technology, and tools are to meet the current time and the future. Plant GE can make a real difference to future sustainable food production to the benefit of both mankind and our environment.European Cooperation in Science and Technology (COST) CA18111info:eu-repo/semantics/publishedVersio

The genomics of heart failure: design and rationale of the HERMES consortium

AIMS: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. METHODS AND RESULTS: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01–0.05) at P < 5 × 10^{-8} under an additive genetic model. CONCLUSIONS: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction

Genome-wide association study for incident myocardial infarction and coronary heart disease in prospective cohort studies: The CHARGE Consortium

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10−6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10−6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10−3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10−9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10−3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.