Unusual distribution pattern of telomeric repeats in the shrews <Emphasis Type="Italic">Sorex araneus</Emphasis> and <Emphasis Type="Italic">Sorex granarius</Emphasis>

Sorex araneus and Sorex granarius are sibling species within the Sorex araneus group with karyotypes composed of almost identical chromosome arms. S. granarius has a largely acrocentric karyotype, while, in S. araneus, various of these acrocentrics have combined together by Robertsonian (Rb) fusions to form metacentrics, with the numbers and types of metacentrics differing between chromosomal races. Our studies on telomeric sequences in S. araneus and S. granarius revealed differences between chromosomes and between species. In S. araneus (the Novosibirsk race), hybridization signals were present on the telomeres of all the chromosomes after FISH with a PCR-generated telomeric probe. In addition, hybridization signals were observed at high frequencies in the pericentric regions of some but not all metacentrics formed by Rb fusion. There were fewer signals on those metacentrics formed earlier in the evolution of S. araneus. This suggests that S. araneus chromosomes retain at least some telomeric repeats during Rb fusion, but that these repeats are lost or modified over time. These results are critical for the interpretation of the well-studied hybrid zones between chromosomal races of S. araneus, given that Rb fission has been postulated in such hybrid zones and that the likelihood of Rb fission will relate to presence/absence of telomeric sequences at the centromeres of metacentrics. In S. granarius, there were strong signals at the proximal (centromeric) telomeres of the acrocentrics after FISH with a DNA telomeric probe. FISH with a PNA telomeric probe on S. granarius acrocentrics showed that the proximal telomeres were 213 kb on average, while the length of the distal telomeres was 3.8 kb on average. Two-colour FISH, using a telomeric DNA probe and a microdissected probe generated from the pericentric regions of the S. granarius chromosomes a and b, revealed regions on distinct chromatin fibres where telomeric and microdissected probes were colocalized or localized sequentially. The proximal telomeres of S. granarius are highly unusual both in their large size and their heterogeneous structure relative to the telomeres of other mammals.     

Ribosomal DNA locus evolution in Nemesia: transposition rather than structural rearrangement as the key mechanism?

We investigated chromosome evolution in Nemesia using fluorescent in-situ hybridization (FISH) to identify the locations of 5S and 45S (18–26S) ribosomal genes. Although there was conservation between Nemesia species in chromosome number, size and centromere position, there was large variation in both number and position of ribosomal genes in different Nemesia species (21 different arrangements of 45S and 5S rRNA genes were observed in the 29 Nemesia taxa studied). Nemesia species contained between one and three pairs of 5S arrays and between two and four pairs of 45S arrays. These were either sub-terminally or interstitially located and 45S and 5S arrays were often located on the same chromosome pair. Comparison of the positions of rDNA arrays with meiotic chromosome behaviour in interspecific hybrids of Nemesia suggests that some of the changes in the positions of rDNA have not affected the surrounding chromosome regions, indicating that rDNA has changed position by transposition. Chromosome evolution is frequently thought to occur via structural rearrangements such as inversions and translocations. We suggest that, in Nemesia, transposition of rDNA genes may be equally if not more important in chromosome evolution.     

Selective labeling of sensory hair cells and neurons in auditory, vestibular, and lateral line systems by a monoclonal antibody

This study reports that zn-1, a monoclonal antibody, labels hair cells but not supporting cells in the inner ear and the lateral line of the axolotl salamander, Ambystoma mexicanum. Zn-1 immunocytochemically labels the cytoplasm and stereocilia of mature hair cells in the sacculus, in the utriculus, and in the mechanoreceptive neuromast organs of the lateral line. Lower levels of labeling mark newly formed hair cells in the periphery of the sacculus and in regenerating neuromasts. Zn-1 also selectively labels neuronal processes and perikarya in the lateral line nerves and ganglia and the VIIIth cranial nerve and ganglion. Processes and perikarya are labeled by zn-1 in the dorsolateral medulla oblongata, at sites of termination of the afferent octaval and lateral line neurons. Western blot analysis revealed that zn-1 labels one or more proteins with molecular weights of 80 and 160 kDa. The identity of these protein bands remains to be determined. The presence of a specific epitope expressed in both hair cells and neurons, but not in supporting cells, in the vestibular and auditory epithelia of the ear and in the mechanoreceptive neuromasts of the lateral line suggests shared cytogenetic heritages. These findings are consistent with a close evolutionary relationship between otic and lateral line senses, such as that inherent to the theoretical evolutionary scheme outlined in van Bergeijk's "acousticolateralis hypothesis." The protein recognized by zn-1 is as yet unidentified, but its conservative evolution suggests that it may serve an important function in the statoacoustic and lateral line systems.     

Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022

Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several nonendemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV-2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV-2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV-2022 strains, including 24 nonsynonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that 10 proteins in the MPXV are more prone to mutation, including D2L-like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L-like, OPG153, OPG188, and OPG210 proteins. In the MPXV-2022 strains, four and three nucleotide substitutions are observed in OPG105 and OPG210, respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.     

Molecular evolution of SARS-CoV-2 from December 2019 to August 2022

Severe acute respiratorysyndrome coronavirus-2 (SARS-CoV-2) pandemic spread rapidly and this scenario is concerning worldwide, presenting more than 590 million coronavirus disease 2019 cases and 6.4 million deaths. The emergence of novel lineages carrying several mutations in the spike protein has raised additional public health concerns worldwide during the pandemic. The present study review and summarizes the temporal spreading and molecular evolution of SARS-CoV-2 clades and variants worldwide. The evaluation of these data is important for understanding the evolutionary histories of SARSCoV-2 lineages, allowing us to identify the origins of each lineage of this virus responsible for one of the biggest pandemics in history. A total of 2897 SARS-CoV-2 whole-genome sequences with available information from the country and sampling date (December 2019 to August 2022), were obtained and were evaluated by Bayesian approach. The results demonstrated that the SARS-CoV-2 the time to the most recent common ancestor (tMRCA) in Asia was 2019-12-26 (highest posterior density 95% [HPD95%]: 2019-12-18; 2019-12-29), in Oceania 2020-01-24 (HPD95%: 2020-01-15; 2020-01-30), in Africa 2020-02-27 (HPD95%: 2020-02-21; 2020-03-04), in Europe 2020-02-27 (HPD95%: 2020-02-20; 2020-03-06), in North America 2020-03-12 (HPD95%: 2020-03-05; 2020-03-18), and in South America 2020-03-15 (HPD95%: 2020-03-09; 2020-03-28). Between December 2019 and June 2020, 11 clades were detected (20I [Alpha] and 19A, 19B, 20B, 20C, 20A, 20D, 20E [EU1], 20F, 20H [Beta]). From July to December 2020, 4 clades were identified (20J [Gamma, V3], 21 C [Epsilon], 21D [Eta], and 21G [Lambda]). Between January and June 2021, 3 clades of the Delta variant were detected (21A, 21I, and 21J). Between July and December 2021, two variants were detected, Delta (21A, 21I, and 21J) and Omicron (21K, 21L, 22B, and 22C). Between January and June 2022, the Delta (21I and 21J) and Omicron (21K, 21L, and 22A) variants were detected. Finally, between July and August 2022, 3 clades of Omicron were detected (22B, 22C, and 22D). Clade 19A was first detected in the SARS-CoV-2 pandemic (Wuhan strain) with origin in 2019-12-16 (HPD95%: 2019-12-15; 2019-12-25); 20I (Alpha) in 2020-11-24 (HPD95%: 2020-11-15; 2021-12-02); 20H (Beta) in 2020-11-25 (HPD95%: 2020-11-13; 2020-11-29); 20J (Gamma) was 2020-12-21 (HPD95%: 2020-11-05; 2021-01-15); 21A (Delta) in 2020-09-20 (HPD95%: 2020-05-17; 2021-02-03); 21J (Delta) in 2021-02-26 (2020-11-02; 2021-04-24); 21M (Omicron) in 2021-01-25 (HPD95%: 2020-09-16; 2021-08-08); 21K (Omicron) in 2021-07-30 (HPD95%: 2021-05-30; 2021-10-19); 21L (Omicron) in 2021-10-03 (HPD95%: 2021-04-16; 2021-12-23); 22B (Omicron) in 2022-01-25 (HPD95%: 2022-01-10; 2022-02-05); 21L in 2021-12-20 (HPD95%: 2021-05-16; 2021-12-31). Currently, the Omicron variant predominates worldwide, with the 21L clade branching into 3 (22A, 22B, and 22C). Phylogeographic data showed that Alpha variant originated in the United Kingdom, Beta in South Africa, Gamma in Brazil, Delta in India, Omicron in South Africa, Mu in Colombia, Epsilon in the United States of America, and Lambda in Peru. The COVID-19 pandemic has had a significant impact on global health worldwide and the present study provides an overview of the molecular evolution of SARS-CoV-2 lineage clades (from the Wuhan strain to the currently circulating lineages of the Omicron).     

Structure and evolution of neuronal wiring receptors and ligands

One of the fundamental properties of a neuronal circuit is the map of its connections. The cellular and developmental processes that allow for the growth of axons and dendrites, selection of synaptic targets, and formation of functional synapses use neuronal surface receptors and their interactions with other surface receptors, secreted ligands, and matrix molecules. Spatiotemporal regulation of the expression of these receptors and cues allows for specificity in the developmental pathways that wire stereotyped circuits. The families of molecules controlling axon guidance and synapse formation are generally conserved across animals, with some important exceptions, which have consequences for neuronal connectivity. Here, we summarize the distribution of such molecules across multiple taxa, with a focus on model organisms, evolutionary processes that led to the multitude of such molecules, and functional consequences for the diversification or loss of these receptors.     

Molecular genetic studies of early breast cancer evolution

Summary In the past few years there has been an explosion in the number of patients diagnosed with hyperplastic breast disease andin situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be initiated (e.g. atypical ductal hyperplasia [ADH]), and early transformed lesions which are malignant but not yet invasive (e.g. ductal carcinomain situ [DCIS]). They may represent sequential evolutionary stages in the ontogeny of invasive breast cancer, with each morphologically defined stage resulting from accumulating genetic changes culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH) and 80% of the DCIS shared their LOH patterns with more advanced lesions from the same breast, strongly supporting a precursor/product relationship between these lesions and the cancers they accompany.     

Genetic evolution of breast cancers III: Age-dependent variations in the correlations between biological indicators of prognosis

The influence of age on the occurrence of phenotypic features of prognostic significance was studied in relation to the DNA index values, measured on DNA histograms from a series of 1019 breast cancer patients. Globally, the distributions of all parameters showed variations with age, the most prominent being the decreases in the percentage of estrogen receptor-negative and high proliferative activity cases with increasing age. When analyzed according to the DNA index classes, all parameters were found to some extent linked with the stage of genetic evolution. However, the associations varied with age, defining two extreme groups. The younger patients (less than 40 years) presented a more complete acquisition of the aggressive phenotype and near-triploid tumors from this group were very frequently steroid hormone receptor-negative, high proliferation, and grade III. By contrast, near-triploid tumors in patients above 65 presented relatively frequently as receptor-positive, low proliferative activity, and even grade I. The correlation of the proliferative status with steroid hormone receptor content led to similar conclusions, high proliferation being more strongly correlated with the absence of estrogen and progesterone receptors in younger patients. Interestingly, the association between high proliferation and negative progesterone receptors was much weaker in patients above 55. Our results suggest that the currently established biological prognostic factors, including DNA profile, steroid hormone receptors, and histopathological grade, show patterns of association which vary with age. Of these, only progesterone receptor could be influenced by menopausal status. These findings have to be taken into consideration for future prognostic factor-related treatment decisions, but also for future methodological improvements of multivariate survival analyses.     

Organization of visual cortex in the northern quoll, Dasyurus hallucatus: evidence for a homologue of the second visual area in marsupials

Two visual areas, V1 and V2 (first and second visual areas), appear to be present in the posterior neocortex of all eutherian mammals investigated so far. However, previous studies have not established whether an area homologous to V2 also exists in metatherian mammals (marsupials). Using electrophysiological techniques, we mapped the visual receptive fields of neurons in the striate and peristriate cortices of the northern quoll, an Australian marsupial. We found that neurons in a 2-mm-wide strip of cortex rostrolateral to V1 form a single, relatively simple representation of the complete contralateral hemifield. This area resembles V2 of eutherians in several respects: (i) neurons in the medial half of the peristriate area represent the lower visual quadrant, whereas those in the lateral half represent the upper visual quadrant; (ii) the vertical meridian of the visual field is represented adjacent to V1, while the visual field periphery is represented along the lateral and rostrolateral borders of the peristriate area; (iii) there is a marked anisotropy in the representation, with a larger magnification factor parallel to the V1 border than perpendicular to this border; and (iv) receptive fields of multiunit clusters in the peristriate cortex are much larger than those of cells in V1 at comparable eccentricities. The cortex immediately rostral and lateral to V2 did not respond to visual stimulation under our recording conditions. These results suggest that V1 and V2 together form a 'core' of homologous visual areas, likely to exist in all therian mammals.     

Progressive ECG changes in arrhythmogenic right ventricular disease Evidence foran evolving disease

Electrocardiography results were used to assess diagnosis andevolution of arrhythmogenic right ventricular disease. The initialECG presentation and long-term changes were analysed in 74consecutivepatients with symptomatic ventricular tachycardia and arrhythmogenicright ventricular disease. On first available tracings, a left axis deviation of the QRSwas found in 18 patients. The QRS length in V¹ was 110 ms in39 patients, an epsilon wave was present in 17, and a completenght bundle branch block in four patients. The T wave was negativein V₁–V₃ in 37 patients (50%). In 36 patients, long-term electrocardiographic follow-up of9.5 ± 3.2 years was available. During this period, ECGchanges were observed in 20 patients (56%):negative T wavesin 11 patients, a new left axis deviation in three, QRS enlargementin 13 (including eight right bundle branch block), right atrialhypertrophy in three, and paroxysmal or established atrial fibrillationin three. On studying all 110 ECG tracings (74 initial recordings +36follow-up ECGs), we found a strong correlation between QRS orT wave changes and the length of follow-up after the first symptom;mean time interval between first ventricular tachycardia andECG recording was significantly longer in patients with negativeT waves in the right precordial leads, QRS enlargement, or leftaxis deviation, than in patients without such abnormalities.ECG abnormalities were more frequent at 10 year and 5 year follow-upthan on initial tracings. A normal ECG was found in 40% of patientsduring the first year of follow-up, 8% at 5 years, and neverlater than the 6th year. In conclusion, electrocardiographic diagnosis of arrhythmogenicright ventricular disease may be difficult in the initial stageof the disease, since a normal ECG is found in up to 40% ofpatients. During the follow-up, progressive and characteristicECG changes will occur. Arrhythmogenic right ventricular diseasecan be excluded if the ECG is found to be normal 6 years orlater after a first ventricular tachycardia attack.