Muséum national d'Histoire naturelle

It is often claimed that we do not understand the forces driving the global diversity gradient. However, an extensive literature suggests that contemporary climate constrains terrestrial taxonomic richness over broad geographic extents. Here, we review the empirical literature to examine the nature and form of the relationship between climate and richness. Our goals were to document the support for the climatically based energy hypothesis, and within the constraints imposed by correlative analyses, to evaluate two versions of the hypothesis: the productivity and ambient energy hypotheses. Focusing on studies extending over 800 km, we found that measures of energy, water, or water–energy balance explain spatial variation in richness better than other climatic and non-climatic variables in 82 of 85 cases. Even when considered individually and in isolation, water/energy variables explain on average over 60% of the variation in the richness of a wide range of plant and animal groups. Further, water variables usually represent the strongest predictors in the tropics, subtropics, and warm temperate zones, whereas energy variables (for animals) or water–energy variables (for plants) dominate in high latitudes. We conclude that the interaction between water and energy, either directly or indirectly (via plant productivity), provides a strong explanation for globally extensive plant and animal diversity gradients, but for animals there also is a latitudinal shift in the relative importance of ambient energy vs. water moving from the poles to the equator. Although contemporary climate is not the only factor influencing species richness and may not explain the diversity pattern for all taxonomic groups, it is clear that understanding water–energy dynamics is critical to future biodiversity research. Analyses that do not include water–energy variables are missing a key component for explaining broad-scale patterns of diversity.

BACKGROUND: The success of the CRISPR/Cas9 genome editing technique depends on the choice of the guide RNA sequence, which is facilitated by various websites. Despite the importance and popularity of these algorithms, it is unclear to which extent their predictions are in agreement with actual measurements. RESULTS: We conduct the first independent evaluation of CRISPR/Cas9 predictions. To this end, we collect data from eight SpCas9 off-target studies and compare them with the sites predicted by popular algorithms. We identify problems in one implementation but found that sequence-based off-target predictions are very reliable, identifying most off-targets with mutation rates superior to 0.1 %, while the number of false positives can be largely reduced with a cutoff on the off-target score. We also evaluate on-target efficiency prediction algorithms against available datasets. The correlation between the predictions and the guide activity varied considerably, especially for zebrafish. Together with novel data from our labs, we find that the optimal on-target efficiency prediction model strongly depends on whether the guide RNA is expressed from a U6 promoter or transcribed in vitro. We further demonstrate that the best predictions can significantly reduce the time spent on guide screening. CONCLUSIONS: To make these guidelines easily accessible to anyone planning a CRISPR genome editing experiment, we built a new website ( http://crispor.org ) that predicts off-targets and helps select and clone efficient guide sequences for more than 120 genomes using different Cas9 proteins and the eight efficiency scoring systems evaluated here.

Specialization is a concept based on a broad theoretical framework developed by evolutionary biologists and ecologists. In the past 10 years, numerous studies have reported that – in many contexts – generalist species are “replacing” specialist species. We review recent research on the concept of the ecological niche and species specialization, and conclude that (1) the observed worldwide decline in specialist species is predicted by niche theory, (2) specialist declines cause “functional homogenization” of biodiversity, and (3) such homogenization may be used to measure the impact of disturbance on communities. Homogenization at the community level could alter ecosystem functioning and productivity, as well as result in the deterioration of ecosystem goods and services. We propose community‐level specialization as an indicator of the impact of global changes (habitat and climate disturbances) on biodiversity.

Ecosystem reconfigurations arising from climate-driven changes in species distributions are expected to have profound ecological, social, and economic implications. Here we reveal a rapid climate-driven regime shift of Australian temperate reef communities, which lost their defining kelp forests and became dominated by persistent seaweed turfs. After decades of ocean warming, extreme marine heat waves forced a 100-kilometer range contraction of extensive kelp forests and saw temperate species replaced by seaweeds, invertebrates, corals, and fishes characteristic of subtropical and tropical waters. This community-wide tropicalization fundamentally altered key ecological processes, suppressing the recovery of kelp forests.

Sequencing of the genome of the butterfly Heliconius melpomene shows that closely related Heliconius species exchange protective colour-pattern genes promiscuously. Heliconius butterflies are an excellent system in which to study ecology, behaviour, mimicry and speciation. The genome of the postman butterfly Heliconius melpomene has now been sequenced. Using genomic resequencing of individuals from distinct lineages, the authors document heterogenous patterns of genomic diversity associated with adaptively divergent wing-colour patterns. As the second lepidopteran genome to be sequenced, Heliconius offers novel opportunities for comparative genomics within this economically significant insect order, which includes many pest species, as well as the only domesticated insect, the silkmoth Bombyx mori. The evolutionary importance of hybridization and introgression has long been debated1. Hybrids are usually rare and unfit, but even infrequent hybridization can aid adaptation by transferring beneficial traits between species. Here we use genomic tools to investigate introgression in Heliconius, a rapidly radiating genus of neotropical butterflies widely used in studies of ecology, behaviour, mimicry and speciation2,3,4,5. We sequenced the genome of Heliconius melpomene and compared it with other taxa to investigate chromosomal evolution in Lepidoptera and gene flow among multiple Heliconius species and races. Among 12,669 predicted genes, biologically important expansions of families of chemosensory and Hox genes are particularly noteworthy. Chromosomal organization has remained broadly conserved since the Cretaceous period, when butterflies split from the Bombyx (silkmoth) lineage. Using genomic resequencing, we show hybrid exchange of genes between three co-mimics, Heliconius melpomene, Heliconius timareta and Heliconius elevatus, especially at two genomic regions that control mimicry pattern. We infer that closely related Heliconius species exchange protective colour-pattern genes promiscuously, implying that hybridization has an important role in adaptive radiation.

Abstract Broad‐scale variation in taxonomic richness is strongly correlated with climate. Many mechanisms have been hypothesized to explain these patterns; however, testable predictions that would distinguish among them have rarely been derived. Here, we examine several prominent hypotheses for climate–richness relationships, deriving and testing predictions based on their hypothesized mechanisms. The ‘energy–richness hypothesis’ (also called the ‘more individuals hypothesis’) postulates that more productive areas have more individuals and therefore more species. More productive areas do often have more species, but extant data are not consistent with the expected causal relationship from energy to numbers of individuals to numbers of species. We reject the energy–richness hypothesis in its standard form and consider some proposed modifications. The ‘physiological tolerance hypothesis’ postulates that richness varies according to the tolerances of individual species for different sets of climatic conditions. This hypothesis predicts that more combinations of physiological parameters can survive under warm and wet than cold or dry conditions. Data are qualitatively consistent with this prediction, but are inconsistent with the prediction that species should fill climatically suitable areas. Finally, the ‘speciation rate hypothesis’ postulates that speciation rates should vary with climate, due either to faster evolutionary rates or stronger biotic interactions increasing the opportunity for evolutionary diversification in some regions. The biotic interactions mechanism also has the potential to amplify shallower, underlying gradients in richness. Tests of speciation rate hypotheses are few (to date), and their results are mixed.

Abstract Invertebrate species represent more than 99% of animal diversity; however, they receive much less publicity and attract disproportionately minor research effort relative to vertebrates. Nonmarine mollusks (i.e., terrestrial and freshwater) are one of the most diverse and imperiled groups of animals, although not many people other than a few specialists who study the group seem to be aware of their plight. Nonmarine mollusks include a number of phylogenetically disparate lineages and species-rich assemblages that represent two molluscan classes, Bivalvia (clams and mussels) and Gastropoda (snails, slugs, and limpets). In this article we provide an overview of global nonmarine molluscan biodiversity and conservation status, including several case studies documenting the diversity and global decline of nonmarine mollusks. We conclude with a discussion of the roles that mollusks and malacologists should play in conservation, including research, conservation management strategies, and education and outreach.

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification. Genomes and transcriptomes of five distinct lineages of African cichlids, a textbook example of adaptive radiation, have been sequenced and analysed to reveal that many types of molecular changes contributed to rapid evolution, and that standing variation accumulated during periods of relaxed selection may have primed subsequent diversification. The 2,000 or so species of cichlid fish, to be found in the lakes and rivers of Africa's Rift Valley, provide the classic example of adaptive radiations. This large-scale international collaboration has sequenced and analysed the genomes and transcriptomes of five distinct lineages of African cichlids. The data reveal an excess of gene duplications in comparison to other fish species. There is an abundance of non-coding element divergence; accelerated coding sequence evolution; expression divergence associated with transposable element insertions in orthologous gene pairs; and regulation by novel miRNAs. Sequencing data from sixty individuals from six closely related Lake Victoria species point to rapid cichlid speciation associated with genome-wide diversifying selection on coding and regulatory variants, and imply that ancient periods of relaxed purifying selection enabled the accumulation of standing variation, which may have been important in facilitating diversification.

The Stardust spacecraft collected thousands of particles from comet 81P/Wild 2 and returned them to Earth for laboratory study. The preliminary examination of these samples shows that the nonvolatile portion of the comet is an unequilibrated assortment of materials that have both presolar and solar system origin. The comet contains an abundance of silicate grains that are much larger than predictions of interstellar grain models, and many of these are high-temperature minerals that appear to have formed in the inner regions of the solar nebula. Their presence in a comet proves that the formation of the solar system included mixing on the grandest scales.

Wetlands are among the most productive and economically valuable ecosystems in the world. However, because of human activities, over half of the wetland ecosystems existing in North America, Europe, Australia, and China in the early 20th century have been lost. Ecological restoration to recover critical ecosystem services has been widely attempted, but the degree of actual recovery of ecosystem functioning and structure from these efforts remains uncertain. Our results from a meta-analysis of 621 wetland sites from throughout the world show that even a century after restoration efforts, biological structure (driven mostly by plant assemblages), and biogeochemical functioning (driven primarily by the storage of carbon in wetland soils), remained on average 26% and 23% lower, respectively, than in reference sites. Either recovery has been very slow, or postdisturbance systems have moved towards alternative states that differ from reference conditions. We also found significant effects of environmental settings on the rate and degree of recovery. Large wetland areas (>100 ha) and wetlands restored in warm (temperate and tropical) climates recovered more rapidly than smaller wetlands and wetlands restored in cold climates. Also, wetlands experiencing more (riverine and tidal) hydrologic exchange recovered more rapidly than depressional wetlands. Restoration performance is limited: current restoration practice fails to recover original levels of wetland ecosystem functions, even after many decades. If restoration as currently practiced is used to justify further degradation, global loss of wetland ecosystem function and structure will spread.

Abstract— In the primordial solar system, the most plausible sources of the water accreted by the Earth were in the outer asteroid belt, in the giant planet regions, and in the Kuiper Belt. We investigate the implications on the origin of Earth's water of dynamical models of primordial evolution of solar system bodies and check them with respect to chemical constraints. We find that it is plausible that the Earth accreted water all along its formation, from the early phases when the solar nebula was still present to the late stages of gas‐free sweepup of scattered planetesimals. Asteroids and the comets from the Jupiter‐Saturn region were the first water deliverers, when the Earth was less than half its present mass. The bulk of the water presently on Earth was carried by a few planetary embryos, originally formed in the outer asteroid belt and accreted by the Earth at the final stage of its formation. Finally, a late veneer, accounting for at most 10% of the present water mass, occurred due to comets from the Uranus‐Neptune region and from the Kuiper Belt. The net result of accretion from these several reservoirs is that the water on Earth had essentially the D/H ratio typical of the water condensed in the outer asteroid belt. This is in agreement with the observation that the D/H ratio in the oceans is very close to the mean value of the D/H ratio of the water inclusions in carbonaceous chondrites.

Covering: up to June 2020Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large group of natural products. A community-driven review in 2013 described the emerging commonalities in the biosynthesis of RiPPs and the opportunities they offered for bioengineering and genome mining. Since then, the field has seen tremendous advances in understanding of the mechanisms by which nature assembles these compounds, in engineering their biosynthetic machinery for a wide range of applications, and in the discovery of entirely new RiPP families using bioinformatic tools developed specifically for this compound class. The First International Conference on RiPPs was held in 2019, and the meeting participants assembled the current review describing new developments since 2013. The review discusses the new classes of RiPPs that have been discovered, the advances in our understanding of the installation of both primary and secondary post-translational modifications, and the mechanisms by which the enzymes recognize the leader peptides in their substrates. In addition, genome mining tools used for RiPP discovery are discussed as well as various strategies for RiPP engineering. An outlook section presents directions for future research.

Background: Pollution - unwanted waste released to air, water, and land by human activity - is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood. Goals: (1) Broadly examine the known and potential impacts of ocean pollution on human health. (2) Inform policy makers, government leaders, international organizations, civil society, and the global public of these threats. (3) Propose priorities for interventions to control and prevent pollution of the seas and safeguard human health. Methods: Topic-focused reviews that examine the effects of ocean pollution on human health, identify gaps in knowledge, project future trends, and offer evidence-based guidance for effective intervention. Environmental Findings: Pollution of the oceans is widespread, worsening, and in most countries poorly controlled. It is a complex mixture of toxic metals, plastics, manufactured chemicals, petroleum, urban and industrial wastes, pesticides, fertilizers, pharmaceutical chemicals, agricultural runoff, and sewage. More than 80% arises from land-based sources. It reaches the oceans through rivers, runoff, atmospheric deposition and direct discharges. It is often heaviest near the coasts and most highly concentrated along the coasts of low- and middle-income countries. Plastic is a rapidly increasing and highly visible component of ocean pollution, and an estimated 10 million metric tons of plastic waste enter the seas each year. Mercury is the metal pollutant of greatest concern in the oceans; it is released from two main sources - coal combustion and small-scale gold mining. Global spread of industrialized agriculture with increasing use of chemical fertilizer leads to extension of Harmful Algal Blooms (HABs) to previously unaffected regions. Chemical pollutants are ubiquitous and contaminate seas and marine organisms from the high Arctic to the abyssal depths. Ecosystem Findings: species. Industrial discharges, pharmaceutical wastes, pesticides, and sewage contribute to global declines in fish stocks. Human Health Findings: infections, including cholera, will increase in frequency and extend to new areas. All of the health impacts of ocean pollution fall disproportionately on vulnerable populations in the Global South - environmental injustice on a planetary scale. Conclusions: Ocean pollution is a global problem. It arises from multiple sources and crosses national boundaries. It is the consequence of reckless, shortsighted, and unsustainable exploitation of the earth's resources. It endangers marine ecosystems. It impedes the production of atmospheric oxygen. Its threats to human health are great and growing, but still incompletely understood. Its economic costs are only beginning to be counted.Ocean pollution can be prevented. Like all forms of pollution, ocean pollution can be controlled by deploying data-driven strategies based on law, policy, technology, and enforcement that target priority pollution sources. Many countries have used these tools to control air and water pollution and are now applying them to ocean pollution. Successes achieved to date demonstrate that broader control is feasible. Heavily polluted harbors have been cleaned, estuaries rejuvenated, and coral reefs restored.Prevention of ocean pollution creates many benefits. It boosts economies, increases tourism, helps restore fisheries, and improves human health and well-being. It advances the Sustainable Development Goals (SDG). These benefits will last for centuries. Recommendations: World leaders who recognize the gravity of ocean pollution, acknowledge its growing dangers, engage civil society and the global public, and take bold, evidence-based action to stop pollution at source will be critical to preventing ocean pollution and safeguarding human health.Prevention of pollution from land-based sources is key. Eliminating coal combustion and banning all uses of mercury will reduce mercury pollution. Bans on single-use plastic and better management of plastic waste reduce plastic pollution. Bans on persistent organic pollutants (POPs) have reduced pollution by PCBs and DDT. Control of industrial discharges, treatment of sewage, and reduced applications of fertilizers have mitigated coastal pollution and are reducing frequency of HABs. National, regional and international marine pollution control programs that are adequately funded and backed by strong enforcement have been shown to be effective. Robust monitoring is essential to track progress.Further interventions that hold great promise include wide-scale transition to renewable fuels; transition to a circular economy that creates little waste and focuses on equity rather than on endless growth; embracing the principles of green chemistry; and building scientific capacity in all countries.Designation of Marine Protected Areas (MPAs) will safeguard critical ecosystems, protect vulnerable fish stocks, and enhance human health and well-being. Creation of MPAs is an important manifestation of national and international commitment to protecting the health of the seas.

Horse domestication revolutionized transport, communications, and warfare in prehistory, yet the identification of early domestication processes has been problematic. Here, we present three independent lines of evidence demonstrating domestication in the Eneolithic Botai Culture of Kazakhstan, dating to about 3500 B.C.E. Metrical analysis of horse metacarpals shows that Botai horses resemble Bronze Age domestic horses rather than Paleolithic wild horses from the same region. Pathological characteristics indicate that some Botai horses were bridled, perhaps ridden. Organic residue analysis, using delta13C and deltaD values of fatty acids, reveals processing of mare's milk and carcass products in ceramics, indicating a developed domestic economy encompassing secondary products.

Oligodeoxynucleotides which include stretches of guanines form a well-known tetrameric structure. We show that the recording of reversible absorbance changes at 295 nm allows to precisely monitor intramolecular guanine (G)-quartet formation and dissociation. Accurate Tm and thermodynamic values could be easily extracted from the data, whereas classical recordings at 260 nm led to a much larger uncertainty and in extreme cases, to completely inaccurate measurements. This inverted denaturation profile was observed for all G-quartet-forming oligonucleotides studied so far. This technique is very useful in all cases where intramolecular or intermolecular quadruplex formation is suspected.

Archaeological excavations at the site of Dmanisi in the Republic of Georgia have uncovered two partial early Pleistocene hominid crania. The new fossils consist of a relatively complete cranium and a second relatively complete calvaria from the same site and stratigraphic unit that yielded a hominid mandible in 1991. In contrast with the uncertain taxonomic affinity of the mandible, the new fossils are comparable in size and morphology with Homo ergaster from Koobi Fora, Kenya. Paleontological, archaeological, geochronological, and paleomagnetic data from Dmanisi all indicate an earliest Pleistocene age of about 1.7 million years ago, supporting correlation of the new specimens with the Koobi Fora fossils. The Dmanisi fossils, in contrast with Pleistocene hominids from Western Europe and Eastern Asia, show clear African affinity and may represent the species that first migrated out of Africa.

Sequence-specific nucleases like TALENs and the CRISPR/Cas9 system have greatly expanded the genome editing possibilities in model organisms such as zebrafish. Both systems have recently been used to create knock-out alleles with great efficiency, and TALENs have also been successfully employed in knock-in of DNA cassettes at defined loci via homologous recombination (HR). Here we report CRISPR/Cas9-mediated knock-in of DNA cassettes into the zebrafish genome at a very high rate by homology-independent double-strand break (DSB) repair pathways. After co-injection of a donor plasmid with a short guide RNA (sgRNA) and Cas9 nuclease mRNA, concurrent cleavage of donor plasmid DNA and the selected chromosomal integration site resulted in efficient targeted integration of donor DNA. We successfully employed this approach to convert eGFP into Gal4 transgenic lines, and the same plasmids and sgRNAs can be applied in any species where eGFP lines were generated as part of enhancer and gene trap screens. In addition, we show the possibility of easily targeting DNA integration at endogenous loci, thus greatly facilitating the creation of reporter and loss-of-function alleles. Due to its simplicity, flexibility, and very high efficiency, our method greatly expands the repertoire for genome editing in zebrafish and can be readily adapted to many other organisms.

The bulk of the comet 81P/Wild 2 (hereafter Wild 2) samples returned to Earth by the Stardust spacecraft appear to be weakly constructed mixtures of nanometer-scale grains, with occasional much larger (over 1 micrometer) ferromagnesian silicates, Fe-Ni sulfides, Fe-Ni metal, and accessory phases. The very wide range of olivine and low-Ca pyroxene compositions in comet Wild 2 requires a wide range of formation conditions, probably reflecting very different formation locations in the protoplanetary disk. The restricted compositional ranges of Fe-Ni sulfides, the wide range for silicates, and the absence of hydrous phases indicate that comet Wild 2 experienced little or no aqueous alteration. Less abundant Wild 2 materials include a refractory particle, whose presence appears to require radial transport in the early protoplanetary disk.

The order Cetartiodactyla includes cetaceans (whales, dolphins and porpoises) that are found in all oceans and seas, as well as in some rivers, and artiodactyls (ruminants, pigs, peccaries, hippos, camels and llamas) that are present on all continents, except Antarctica and until recent invasions, Australia. There are currently 332 recognized cetartiodactyl species, which are classified into 132 genera and 22 families. Most phylogenetic studies have focused on deep relationships, and no comprehensive time-calibrated tree for the group has been published yet. In this study, 128 new complete mitochondrial genomes of Cetartiodactyla were sequenced and aligned with those extracted from nucleotide databases. Our alignment includes 14,902 unambiguously aligned nucleotide characters for 210 taxa, representing 183 species, 107 genera, and all cetartiodactyl families. Our mtDNA data produced a statistically robust tree, which is largely consistent with previous classifications. However, a few taxa were found to be para- or polyphyletic, including the family Balaenopteridae, as well as several genera and species. Accordingly, we propose several taxonomic changes in order to render the classification compatible with our molecular phylogeny. In some cases, the results can be interpreted as possible taxonomic misidentification or evidence for mtDNA introgression. The existence of three new cryptic species of Ruminantia should therefore be confirmed by further analyses using nuclear data. We estimate divergence times using Bayesian relaxed molecular clock models. The deepest nodes appeared very sensitive to prior assumptions leading to unreliable estimates, primarily because of the misleading effects of rate heterogeneity, saturation and divergent outgroups. In addition, we detected that Whippomorpha contains slow-evolving taxa, such as large whales and hippos, as well as fast-evolving taxa, such as river dolphins. Our results nevertheless indicate that the evolutionary history of cetartiodactyls was punctuated by four main phases of rapid radiation during the Cenozoic era: the sudden occurrence of the three extant lineages within Cetartiodactyla (Cetruminantia, Suina and Tylopoda); the basal diversification of Cetacea during the Early Oligocene; and two radiations that involve Cetacea and Pecora, one at the Oligocene/Miocene boundary and the other in the Middle Miocene. In addition, we show that the high species diversity now observed in the families Bovidae and Cervidae accumulated mainly during the Late Miocene and Plio-Pleistocene.

Abstract Nucleic acids can be selectively recognized by a large number of natural and synthetic ligands. Oligonucleotides provide the highest specificity of recognition. They can bind to a complementary single‐stranded sequence by forming Watson–Crick hydrogen bonds. They can also recognize the major groove of double‐helical DNA at specific sequences by forming Hoogsteen or reverse Hoogsteen hydrogen bonds with purine bases of the Watson‐Crick base pairs, resulting in a triple helix. Triple‐helix formation through oligonucleotide binding to DNA is a sequence–specific interaction involving primarily homopurine·homopyrimidine sequences in the double‐helical target. Extending the range of recognition sequences remains a challenge to chemists. Both thermodynamic and kinetic parameters for triplex formation have been determined. These parameters indicate, for example, that triple‐helix formation is a much slower process than duplex formation. Nuclease‐resistant oligonucleotides synthesized with the anomers of nucleosides (instead of the natural β‐anomers) also form triple helices with double–stranded DNA. Triple‐helix‐forming oligonucleotides can be modified, for example, by attaching DNA intercalating agents to enhance their binding affinity. They may also be modified with reagents that induce irreversible reactions in their target sequence upon chemical or photochemical activation. Thus, artificial nucleases can be developed with very high sequence specificity on megabase‐size DNA. Furthermore, triple‐helix‐forming oligonucleotides can be used to selectively control gene expression. When bound to the regulatory region(s) of specific genes they may prevent activation (or repression) of transcription. When binding occurs near or downstream from the transcription initiation site, elongation of the transcript may be inhibited. Therefore, the potential exists for developing new gene‐blocking agents with therapeutic applications in the treatment of gene disorders.