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As the number of single-nucleotide polymorphism (SNP) screening and other mutation scanning studies have increased explosively, following the development of high-throughput instrumentation, it becomes even more important to have sufficient template DNA. The source of DNA is often limited, especially in epidemiological studies, which require many samples as well as enough DNA to perform numerous SNP screenings or mutation scannings. Therefore, the aim is to solve the problem of stock DNA limitation. This need has been an important reason for the development of whole genome amplification (WGA) methods. Several systems are based on Phi29 polymerase multiple displacement amplification (MDA) or on DNA fragmentation (OmniPlex). Using TaqMan SNP genotyping assays, we have tested four WGA systems -- AmpliQ Genomic Amplifier Kit, GenomiPhi, Repli-g, and GenomePlex -- on DNA extracted from Guthrie cards to evaluate the amplification bias, concordance- and call rates, cost efficiency, and flexibility. All systems successfully amplified picograms of DNA from Guthrie cards to micrograms of product without loss of heterozygosity and with minimal allelic bias. A modified AmpliQ set up was chosen for further evaluation. In all, 2,000 SNP genotyping results from amplified and nonamplified samples were compared and the concordance rates between the samples were 99.7%. The call rate using the TaqMan system was 99.8%. DNA extracted from Guthrie cards and amplified with one of the four evaluated WGA systems is applicable in epidemiological genetic screenings. System choice should be based on requirements for system flexibility, product yield, and use in subsequent analysis.

The Venus flytrap sea anemone Actinoscyphia liui inhabits the nutrient-limited deep ocean in the tropical western Pacific. Compared with most other sea anemones, it has undergone a distinct modification of body shape similar to that of the botanic flytrap. However, the molecular mechanism by which such a peculiar sea anemone adapts to a deep-sea oligotrophic environment is unknown. Here, we report the chromosomal-level genome of A. liui constructed from PacBio and Hi-C data. The assembled genome is 522 Mb in size and exhibits a continuous scaffold N50 of 58.4 Mb. Different from most other sea anemones, which typically possess 14-18 chromosomes per haplotype, A. liui has only 11. The reduced number of chromosomes is associated with chromosome fusion, which likely represents an adaptive strategy to economize energy in oligotrophic deep-sea environments. Comparative analysis with other deep-sea sea anemones revealed adaptive evolution in genes related to cellular autophagy (TMBIM6, SESN1, SCOCB and RPTOR) and mitochondrial energy metabolism (MDH1B and KAD2), which may aid in A. liui coping with severe food scarcity. Meanwhile, the genome has undergone at least two rounds of expansion in gene families associated with fast synaptic transmission, facilitating rapid responses to water currents and prey. Positive selection was detected on putative phosphorylation sites of muscle contraction-related proteins, possibly further improving feeding efficiency. Overall, the present study provides insights into the molecular adaptation to deep-sea oligotrophic environments and sheds light upon potential effects of a novel morphology on the evolution of Cnidaria., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

Background: In social groups, dominant individuals may socially inhibit reproduction of subordinates using aggressive interactions or, in the case of highly eusocial insects, pheromonal communication. It has been hypothesized these two modes of reproductive inhibition utilize conserved pathways. Here, we use a comparative framework to investigate the chemical and genomic underpinnings of reproductive dominance in the primitively eusocial wasp Polistes metricus. Our goals were to first characterize transcriptomic and chemical correlates of reproductive dominance and second, to test whether dominance-associated mechanisms in paper wasps overlapped with aggression or pheromone-related gene expression patterns in other species. To explore whether conserved molecular pathways relate to dominance, we compared wasp transcriptomic data to previous studies of gene expression associated with pheromonal communication and queen-worker differences in honey bees, and aggressive behavior in bees, Drosophila, and mice., Results: By examining dominant and subordinate females from queen and worker castes in early and late season colonies, we found that cuticular hydrocarbon profiles and genome-wide patterns of brain gene expression were primarily associated with season/social environment rather than dominance status. In contrast, gene expression patterns in the ovaries were associated primarily with caste and ovary activation. Comparative analyses suggest genes identified as differentially expressed in wasp brains are not related to queen pheromonal communication or caste in bees, but were significantly more likely to be associated with aggression in other insects (bees, flies), and even a mammal (mice)., Conclusions: This study provides the first comprehensive chemical and molecular analysis of reproductive dominance in paper wasps. We found little evidence for a chemical basis for reproductive dominance in P. metricus, and our transcriptomic analyses suggest that different pathways regulate dominance in paper wasps and pheromone response in bees. Furthermore, there was a substantial impact of season/social environment on gene expression patterns, indicating the important role of external cues in shaping the molecular processes regulating behavior. Interestingly, genes associated with dominance in wasps were also associated with aggressive behavior in bees, solitary insects and mammals. Thus, genes involved in social regulation of reproduction in Polistes may have conserved functions associated with aggression in insects and other taxa.

Intelligent design (ID)-the latest incarnation of religious creationism-posits that complex biological features did not accrue gradually via natural evolutionary forces but, instead, were crafted ex nihilo by a cognitive agent. Yet, many complex biological traits are gratuitously complicated, function poorly, and debilitate their bearers. Furthermore, such dysfunctional traits abound not only in the phenotypes but inside the genomes of eukaryotic species. Here, I highlight several outlandish features of the human genome that defy notions of ID by a caring cognitive agent. These range from de novo mutational glitches that collectively kill or maim countless individuals (including embryos and fetuses) to pervasive architectural flaws (including pseudogenes, parasitic mobile elements, and needlessly baroque regulatory pathways) that are endogenous in every human genome. Gross imperfection at the molecular level presents a conundrum for the traditional paradigms of natural theology as well as for recent assertions of ID, but it is consistent with the notion of nonsentient contrivance by evolutionary forces. In this important philosophical sense, the science of evolutionary genetics should rightly be viewed as an ally (not an adversary) of mainstream religions because it helps the latter to escape the profound theological enigmas posed by notions of ID.

Intelligent design (ID)-the latest incarnation of religious creationism-posits that complex biological features did not accrue gradually via natural evolutionary forces but, instead, were crafted ex nihilo by a cognitive agent. Yet, many complex biological traits are gratuitously complicated, function poorly, and debilitate their bearers. Furthermore, such dysfunctional traits abound not only in the phenotypes but inside the genomes of eukaryotic species. Here, I highlight several outlandish features of the human genome that defy notions of ID by a caring cognitive agent. These range from de novo mutational glitches that collectively kill or maim countless individuals (including embryos and fetuses) to pervasive architectural flaws (including pseudogenes, parasitic mobile elements, and needlessly baroque regulatory pathways) that are endogenous in every human genome. Gross imperfection at the molecular level presents a conundrum for the traditional paradigms of natural theology as well as for recent assertions of ID, but it is consistent with the notion of nonsentient contrivance by evolutionary forces. In this important philosophical sense, the science of evolutionary genetics should rightly be viewed as an ally (not an adversary) of mainstream religions because it helps the latter to escape the profound theological enigmas posed by notions of ID.

Further characterization of genetic structural variations should strongly focus on small and endangered local breeds given their role in unraveling genes and structural variants underlying selective pressures and phenotype variation. A comprehensive genome-wide assessment of copy number variations (CNVs) based on whole-genome re-sequencing data was performed on three Brazilian locally adapted cattle breeds (Caracu Caldeano, Crioulo Lageano, and Pantaneiro) using the ARS-UCD1.2 genome assembly. Data from 36 individuals with an average coverage depth of 14.07× per individual was used. A total of 24 945 CNVs were identified distributed among the breeds (Caracu Caldeano = 7285, Crioulo Lageano = 7297, and Pantaneiro = 10 363). Deletion events were 1.75-2.07-fold higher than duplications, and the total length of CNVs is composed mostly of a high number of segments between 10 and 30 kb. CNV regions (CNVRs) are not uniformly scattered throughout the genomes (n = 463), and 105 CNVRs were found overlapping among the studied breeds. Functional annotation of the CNVRs revealed variants with high consequence on protein sequence harboring relevant genes, in which we highlighted the BOLA-DQB, BOLA-DQA5, CD1A, β-defensins, PRG3, and ULBP21 genes. Enrichment analysis based on the gene list retrieved from the CNVRs disclosed over-represented terms (p < 0.01) strongly associated with immunity and cattle resilience to harsh environments. Additionally, QTL associated with body conformation and dairy-related traits were also unveiled within the CNVRs. These results provide better understanding of the selective forces shaping the genome of such cattle breeds and identify traces of natural selection pressures by which these populations have been exposed to challenging environmental conditions., (© 2023 Stichting International Foundation for Animal Genetics.)

In animals, the sequences for controlling gene expression do not concentrate just at the transcription start site of genes, but are frequently thousands to millions of base pairs distal to it. The interaction of these sequences with one another and their transcription start sites is regulated by factors that shape the three-dimensional (3D) organization of the genome within the nucleus. Over the past decade, indirect tools exploiting high-throughput DNA sequencing have helped to map this 3D organization, have identified multiple key regulators of its structure and, in the process, have substantially reshaped our view of how 3D genome architecture regulates transcription. Now, new tools for high-throughput super-resolution imaging of chromatin have directly visualized the 3D chromatin organization, settling some debates left unresolved by earlier indirect methods, challenging some earlier models of regulatory specificity and creating hypotheses about the role of chromatin structure in transcriptional regulation., (© 2022. Springer Nature Limited.)

Evolutionary processes may have substantial impacts on community assembly, but evidence for phylogenetic relatedness as a determinant of interspecific interaction strength remains mixed. In this perspective, we consider a possible role for discordance between gene trees and species trees in the interpretation of phylogenetic signal in studies of community ecology. Modern genomic data show that the evolutionary histories of many taxa are better described by a patchwork of histories that vary along the genome rather than a single species tree. If a subset of genomic loci harbour trait-related genetic variation, then the phylogeny at these loci may be more informative of interspecific trait differences than the genome background. We develop a simple method to detect loci harbouring phylogenetic signal and demonstrate its application through a proof-of-principle analysis of Penicillium genomes and pairwise interaction strength. Our results show that phylogenetic signal that may be masked genome-wide could be detectable using phylogenomic techniques and may provide a window into the genetic basis for interspecific interactions., (© 2024 John Wiley & Sons Ltd.)

Anthropogenic hybridization, or higher and non-natural rates of gene flow directly and indirectly induced by human activities, is considered a significant threat to biodiversity. The primary concern for conservation is the potential for genomic extinction and loss of adaptiveness for native species due to the extensive introgression of non-native genes. To alleviate or reverse trends for such scenarios requires the direct integration of genomic data within a model framework for effective management. Towards this end, we developed the simRestore R program as a decision-making tool that integrates ecological and genomic information to simulate ancestry outcomes from optimized conservation strategies. In short, the program optimizes supplementation and removal strategies across generations until a set native genetic threshold is reached within the studied population. Importantly, in addition to helping with initial decision-making, simulations can be updated with the outcomes of ongoing efforts, allowing for the adaptive management of populations. After demonstrating functionality, we apply and optimize among actionable management strategies for the endangered Hawaiian duck for which the current primary threat is genetic extinction through ongoing anthropogenic hybridization with feral mallards. Simulations demonstrate that supplemental and removal efforts can be strategically tailored to move the genetic ancestry of Hawaii's hybrid populations towards Hawaiian duck without the need to completely start over. Further, we discuss ecological parameter sensitivity, including which factors are most important to ensure genetic outcomes (i.e. number of offspring). Finally, to facilitate use, the program is also available online as a Shiny Web application., (© 2023 John Wiley & Sons Ltd.)

Admixture, the interbreeding of individuals from differentiated source populations, is now known to be a widespread phenomenon. Genomic studies of natural hybridisation can help to answer many questions on the impacts of admixture on adaptive evolution, reproductive isolation, and speciation. When a large variety of admixture proportions between two source populations exist, both geographic and genomic cline analysis are suitable methods for inferring biased, restricted or excessive gene flow at individual loci into the foreign genomic background, providing evidence for reproductive isolation, selection across an environmental transition, balancing selection, and adaptive introgression. Genomic cline analysis replaces geographic location with genome-wide hybrid index and is therefore useable in circumstances that violate geographic cline assumptions. Here, I introduce gghybrid, an R package for simple and flexible Bayesian estimation of Buerkle's hybrid index and Fitzpatrick's logit-logistic genomic clines using bi-allelic data, suitable for both small and large datasets. gghybrid allows any ploidy and uses Structure input file format. It has separate functions for hybrid index and cline estimation, treating each individual and locus respectively as an independent analysis, making it highly parallelisable. Admixture proportions from other software can alternatively be used in cline analysis, alongside parental allele frequencies. Parameters can be fixed and samples pooled for statistical model comparison with AIC or waic. Here, I describe the functions, pipeline, and statistical properties of gghybrid. Simulations reveal that model comparison with waic is preferred, and use of Bayesian posterior distributions and p values to select candidate non-null loci is problematic and should be avoided., (© 2023 John Wiley & Sons Ltd.)

Modern genome-scale methods that identify new genes, such as proteogenomics and ribosome profiling, have revealed, to the surprise of many, that overlap in genes, open reading frames and even coding sequences is widespread and functionally integrated into prokaryotic, eukaryotic and viral genomes. In parallel, the constraints that overlapping regions place on genome sequences and their evolution can be harnessed in bioengineering to build more robust synthetic strains and constructs. With a focus on overlapping protein-coding and RNA-coding genes, this Review examines their discovery, topology and biogenesis in the context of their genome biology. We highlight exciting new uses for sequence overlap to control translation, compress synthetic genetic constructs, and protect against mutation., (© 2021. Springer Nature Limited.)

Via long-term natural and artificial selection pressure, homozygosity may extend across the genome, leaving genomic patterns called selection signatures. This study is the first attempt to assess genome-wide selection signatures in six native Turkish and two cosmopolitan cattle breeds by 211.119 bi-allelic SNPs recovered using the double digest restriction associated DNA sequencing method. The integrated haplotype score (iHS) statistic was utilised to reveal selection signatures within populations, whereas the cross-population extended haplotype homozygosity (XP-EHH) and fixation index (F ST ) approaches were preferred to reveal differently fixed genomic regions between native Turkish and cosmopolitan cattle breeds. Selection signatures in 142 genomic regions containing 305 genes were detected within eight cattle breeds by iHS statistics. The XP-EHH and F ST approaches revealed that 197 and 114 SNPs were under selection pressure, respectively, which overlapped with 144 and 190 genes, respectively. A total of 18 genes were detected by at least two approaches. Six genes related to disease resistance (TTP2), meat yield (DIAPH3 and METTL21C), meat quality (ZNF24 and ZNF397) and first calving interval (ZSCAN30) turned out to be differently fixed between native Turkish and cosmopolitan cattle breeds, as they were identified by both XP-EHH and F ST approaches. In addition, the iHS approach revealed that eight genes associated with visual modality (LSGN), olfaction (MOXD2, OR4C1F and OR4C1F), and immune response (TRBV3-1 and CLDN10) were under selection pressure in both native and cosmopolitan cattle breeds. Owing to their being significantly related to survival traits, these regions may have played a key role in cattle genome evolution. Future studies utilising denser genetic data are required to obtain deeper knowledge on effects of natural and artificial selection in Anatolian cattle breeds. © 2023 Stichting International Foundation for Animal Genetics., (© 2023 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.)

Binge eating disorder (BED) is a complex and heritable mental health disorder, with genetic, neurobiological, neuroendocrinological, environmental and developmental factors all demonstrated to contribute to the aetiology of this illness. Although psychotherapy is the gold standard for treating BED, a significant subgroup of those treated do not recover. Neurobiological research highlights aberrances in neural regions associated with reward processing, emotion processing, self-regulation and executive function processes, which are clear therapeutic targets for future treatment frameworks. Evidence is emerging of the microbiota-gut-brain axis, which may mediate energy balance, high-lighting a possible underlying pathogenesis factor of BED, and provides a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Understanding how chromatin is folded in the nucleus is fundamental to understanding its function. Although 3D genome organization has been historically difficult to study owing to a lack of relevant methodologies, major technological breakthroughs in genome-wide mapping of chromatin contacts and advances in imaging technologies in the twenty-first century considerably improved our understanding of chromosome conformation and nuclear architecture. In this Review, we discuss methods of 3D genome organization analysis, including sequencing-based techniques, such as Hi-C and its derivatives, Micro-C, DamID and others; microscopy-based techniques, such as super-resolution imaging coupled with fluorescence in situ hybridization (FISH), multiplex FISH, in situ genome sequencing and live microscopy methods; and computational and modelling approaches. We describe the most commonly used techniques and their contribution to our current knowledge of nuclear architecture and, finally, we provide a perspective on up-and-coming methods that open possibilities for future major discoveries., (© 2021. Springer Nature Limited.)

The burbot (Lota lota) is the only member of the order Gadiformes adapted solely to freshwater. This species has the widest longitudinal range among freshwater fish worldwide. Burbot serves as a good model for studies on adaptive genome evolution from marine to freshwater environments. However, a high-quality reference genome of burbot has not yet been released. Here, the first chromosome-level genome of burbot was constructed using PacBio long sequencing and Hi-C technology. A total of 95.24 Gb polished PacBio sequences were generated, and the preliminary genome assembly was 575.83 Mb in size with a contig N50 size of 2.15 Mb. The assembled sequences were anchored to 22 pseudochromosomes by using Hi-C data. The final assembled genome after Hi-C correction was 575.92 Mb, with a contig N50 of 2.01 Mb and a scaffold N50 of 22.10 Mb. A total of 22,067 protein-coding genes were predicted, 94.82% of which were functionally annotated. Phylogenetic analyses indicated that burbot diverged with the Atlantic cod approximately 43.8 million years ago. In addition, 377 putative genes that appear to be under positive selection in burbot were identified. These positively selected genes might be involved in the adaptation to the freshwater environment. These genome data provide an invaluable resource for the ecological and evolutionary study of the order Gadiformes., (© 2021 John Wiley & Sons Ltd.)

Taste is essential for the interaction of animals with their food and has co-evolved with diet. Humans have peopled a large range of environments and present a wide range of diets, but little is known about the diversity and evolution of human taste perception. We measured taste recognition thresholds across populations differing in lifestyles (hunter gatherers and farmers from Central Africa, nomad herders, and farmers from Central Asia). We also generated genome-wide genotype data and performed association studies and selection scans in order to link the phenotypic variation in taste sensitivity with genetic variation. We found that hunter gatherers have lower overall sensitivity as well as lower sensitivity to quinine and fructose than their farming neighbors. In parallel, there is strong population divergence in genes associated with tongue morphogenesis and genes involved in the transduction pathway of taste signals in the African populations. We find signals of recent selection in bitter taste-receptor genes for all four populations. Enrichment analysis on association scans for the various tastes confirmed already documented associations and revealed novel GO terms that are good candidates for being involved in taste perception. Our framework permitted us to gain insight into the genetic basis of taste sensitivity variation across populations and lifestyles.

Data taking values on discrete sample spaces are the embodiment of modern biological research. "Omics" experiments based on high-throughput sequencing produce millions of symbolic outcomes in the form of reads (i.e., DNA sequences of a few dozens to a few hundred nucleotides). Unfortunately, these intrinsically non-numerical datasets often deviate dramatically from natural assumptions a practitioner might make, and the possible sources of this deviation are usually poorly characterized. This contrasts with numerical datasets where Gaussian-type errors are often well-justified. To overcome this hurdle, we introduce the notion of latent weight, which measures the largest expected fraction of samples from a probabilistic source that conform to a model in a class of idealized models. We examine various properties of latent weights, which we specialize to the class of exchangeable probability distributions. As proof of concept, we analyze DNA methylation data from the 22 human autosome pairs. Contrary to what is usually assumed in the literature, we provide strong evidence that highly specific methylation patterns are overrepresented at some genomic locations when latent weights are taken into account., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Reproductive traits of dairy cattle are bound to the actual efficiency of farm operation, which therefore show great economic importance. Among them, some traits were deemed to be simultaneously affected by service sire and mating cow. Service sires are proved to play an important role in reproduction process of cows. However, limited study explored the genetic effect of service sire (GESS), let alone the genomic prediction of this effect. In the present study, 2244 genotyped bulls together with phenotypic records were used to predict the GESS on conception rate, 56-day non-return rate, calving ease, stillbirth and gestation length. The feasibilities of multi-step genomic best linear unbiased predictor (msGBLUP) and single-step genomic best linear unbiased predictor (ssGBLUP) were investigated under different scenarios, that is, different marker densities and validation population. The predictive accuracies and unbiasedness for GESS ranged from 0.159 to 0.647 and from 0.202 to 2.018, respectively, when validated on young bulls, while the accuracies and unbiasedness ranged from 0.409 to 0.802 and 0.333 to 1.146 when validated on random split data sets. It is feasible to predict GESS on reproductive traits by using a linear mixed model and genomic data, and high-density marker panel had limited contribution to the prediction. This research investigated the potential factors that influence the genomic prediction of GESS on reproductive traits and indicated the possibility of genomic selection on GESS, both in ideal and practical circumstances., (© 2023 The Authors. Journal of Animal Breeding and Genetics published by John Wiley & Sons Ltd.)

Within the Balkan Peninsula, topographic and climatic agents have promoted biodiversity and shaped the speciation history of many ectotherms. Here, we targeted an iconic European reptile, the nose-horned viper species-complex (Vipera ammodytes), and explored its spatial and temporal evolution. We (i) utilized genome-wide single nucleotide polymorphisms to infer genetic structure and build a time-calibrated species-tree, and (ii) applied species distribution modelling with niche-divergence tests among major phylogenomic clades. Geographically structured genetic diversity was found. Cycles of recurrent isolation and expansion during glacial-interglacial periods led to allopatric speciation and to secondary contacts and formation of multiple hybrid zones throughout the Balkan Peninsula. Deep divergence is still detected among populations separated by old and imminent biogeographical barriers (Pindos Mountain Range, the Cyclades islands, etc.), but in most cases speciation is incomplete. At the other end of the speciation continuum, we recognize two well-differentiated lineages, currently lacking any evidence of gene flow; one is distributed in the Northwestern Balkans and the other in the Southeastern Balkans, further expanding into Asia. Despite their split 5 million years ago, there is no evidence of ecological divergence, as speciation probably occurred in niche-pockets of analogous environments. These two lineages probably represent different species, while V. transcaucasiana does not merit species status. By comparing the genomic phylogenies to an updated mitochondrial one, we propose an evolutionary scenario that resolves all mitonuclear conflicts, according to which the history of the V. ammodytes species-complex was shaped by complex processes, including a major event of introgressive hybridization with asymmetric mitochondrial capture., (© 2023 John Wiley & Sons Ltd.)

Knowing phylogenetic relationships among species is fundamental for many studies in biology. An accurate phylogenetic tree underpins our understanding of the major transitions in evolution, such as the emergence of new body plans or metabolism, and is key to inferring the origin of new genes, detecting molecular adaptation, understanding morphological character evolution and reconstructing demographic changes in recently diverged species. Although data are ever more plentiful and powerful analysis methods are available, there remain many challenges to reliable tree building. Here, we discuss the major steps of phylogenetic analysis, including identification of orthologous genes or proteins, multiple sequence alignment, and choice of substitution models and inference methodologies. Understanding the different sources of errors and the strategies to mitigate them is essential for assembling an accurate tree of life.

In southern Africa, the Nguni cattle breed is classified as an indigenous and transboundary animal genetic resource (AnGR) that manifests unique adaptation abilities across distinct agroecological zones. The genetic integrity of various ecotypes is under potential threat due to both indiscriminate crossbreeding and uncontrolled inbreeding. The aim of this study was to assess the genetic diversity and autozygosity that exist both across countries (ES: eSwatini; SA: South Africa) and within countries (SA), between purebred stud animals (SA-S) and research herds (SA-R). Subsets of 96 ES, 96 SA-S, and 96 SA-R genotyped for 40,930 common SNPs were used to study genome-wide profiles of runs of homozygosity (ROH) and heterozygosity (ROHet) as well as inbreeding levels and population structure. The highest percentage (39.8%) of the 2168 ROH segments was 4-8 Mbp in length, whereas 65% of the 935 ROHet segments fell within the 0.5-1 Mbp length category. Inbreeding coefficients indicated positive but low inbreeding (F ROH>1Mbp range: 0.025 for SA-S to 0.029 for SA-R). Principal component (PCA) and population structure analyses illustrated genome-level distinctness of (1) the Nguni from global indicine (Boran) and taurine (Hereford) breeds (K = 3), (2) the SA Nguni populations from the ES Nguni population (K = 4), and (3) different Nguni ecotypes within countries (K = 8). Furthermore, greater admixture was observed for the SA-R population compared to purebred SA-S population (shared ancestry = 0.631 ± 0.353 compared to 0.741 ± 0.123), and fewer genomics-defined ES ecotypes were observed than phenotypically (pre)defined. Overall, the results illustrated that genetic uniqueness within the sampled Nguni cattle resulted from both geographic isolation and exposure to different breeding strategies (and, selection pressures). A further loss of genetic variability should be monitored to prevent the endangerment of unique and beneficial ecotypes., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Spatiotemporal gene expression programmes are orchestrated by transcriptional enhancers, which are key regulatory DNA elements that engage in physical contacts with their target-gene promoters, often bridging considerable genomic distances. Recent progress in genomics, genome editing and microscopy methodologies have enabled the genome-wide mapping of enhancer-promoter contacts and their functional dissection. In this Review, we discuss novel concepts on how enhancer-promoter interactions are established and maintained, how the 3D architecture of mammalian genomes both facilitates and constrains enhancer-promoter contacts, and the role they play in gene expression control during normal development and disease.

Sophisticated gene-regulatory mechanisms probably evolved in prokaryotes billions of years before the emergence of modern eukaryotes, which inherited the same basic enzymatic machineries. However, the epigenomic landscapes of eukaryotes are dominated by nucleosomes, which have acquired roles in genome packaging, mitotic condensation and silencing parasitic genomic elements. Although the molecular mechanisms by which nucleosomes are displaced and modified have been described, just how transcription factors, histone variants and modifications and chromatin regulators act on nucleosomes to regulate transcription is the subject of considerable ongoing study. We explore the extent to which these transcriptional regulatory components function in the context of the evolutionarily ancient role of chromatin as a barrier to processes acting on DNA and how chromatin proteins have diversified to carry out evolutionarily recent functions that accompanied the emergence of differentiation and development in multicellular eukaryotes.