RESUMEN
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.
Asunto(s)
Ensamble y Desensamble de Cromatina , ADN/genética , Genoma , Nucleosomas/genética , Transcripción Genética , Animales , Evolución Biológica , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/historia , Proteínas Cromosómicas no Histona/metabolismo , ADN/historia , ADN/metabolismo , Células Eucariotas/citología , Células Eucariotas/metabolismo , Genómica/métodos , Histonas/genética , Histonas/historia , Histonas/metabolismo , Historia del Siglo XXI , Historia Antigua , Humanos , Nucleosomas/química , Nucleosomas/metabolismo , Células Procariotas/citología , Células Procariotas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/historia , Factores de Transcripción/metabolismoAsunto(s)
Bioquímica , ADN , Investigadores , Sexismo , ADN/química , ADN/historia , Historia del Siglo XX , Bioquímica/historia , Investigadores/ética , Investigadores/historia , Sexismo/historiaRESUMEN
Peoples speaking so-called Khoisan languages-that is, indigenous languages of southern Africa that do not belong to the Bantu family-are culturally and linguistically diverse. They comprise herders, hunter-gatherers as well as groups of mixed modes of subsistence, and their languages are classified into three distinct language families. This cultural and linguistic variation is mirrored by extensive genetic diversity. We here review the recent genomics literature and discuss the genetic evidence for a formerly wider geographic spread of peoples with Khoisan-related ancestry, for the deep divergence among populations speaking Khoisan languages overlaid by more recent gene flow among these groups and for the impact of admixture with immigrant food-producers in their prehistory.
Asunto(s)
Población Negra/genética , ADN/historia , Lenguaje/historia , África Austral/etnología , Variación Genética , Genética de Población , Genómica , Historia Antigua , HumanosRESUMEN
Africa is the continent with the greatest genetic diversity among humans and the level of diversity is further enhanced by incorporating non-majority groups, which are often understudied. Many of today's minority populations historically practiced foraging lifestyles, which were the only subsistence strategies prior to the rise of agriculture and pastoralism, but only a few groups practicing these strategies remain today. Genomic investigations of Holocene human remains excavated across the African continent show that the genetic landscape was vastly different compared to today's genetic landscape and that many groups that today are population isolate inhabited larger regions in the past. It is becoming clear that there are periods of isolation among groups and geographic areas, but also genetic contact over large distances throughout human history in Africa. Genomic information from minority populations and from prehistoric remains provide an invaluable source of information on the human past, in particular deep human population history, as Holocene large-scale population movements obscure past patterns of population structure. Here we revisit questions on the nature and time of the radiation of early humans in Africa, the extent of gene-flow among human populations as well as introgression from archaic and extinct lineages on the continent.
Asunto(s)
Población Negra/genética , Población Negra/historia , ADN/historia , Genética de Población/métodos , África , Agricultura/historia , Flujo Génico , Variación Genética , Genoma Humano , Historia Antigua , HumanosRESUMEN
The origin of the Malagasy population has been a subject of speculation since the 16th century. Contributions of African, Asian, Indian, Melanesian, Arabic and Persian populations have been suggested based on physical and cultural anthropology, oral tradition, linguistics and later also by archaeology. In the mid-20th century, increased knowledge of heredity rules and technical progress enabled the identification of African and Asian populations as main contributors. Recent access to the genomic landscape of Madagascar demonstrated pronounced regional variability in the relative contributions of these two ancestries, yet with significant presence of both African and Asian components throughout Madagascar. This article reviews the extent to which genetic results have settled historical questions concerning the origin of the Malagasy population. After an overview of the early literature, the genetic results of the 20th and 21th centuries are discussed and then complemented by the latest results in genome-wide analyses. While there is still much uncertainty regarding when, how and the circumstances under which the ancestors of the modern Malagasy population arrived on the island, we propose a scenario based on historical texts and genomic results.
Asunto(s)
Pueblo Asiatico/genética , Población Negra/genética , ADN/historia , Genética de Población/métodos , Antropología Cultural , Variación Genética , Historia Antigua , Migración Humana , Humanos , Lingüística , MadagascarRESUMEN
Compared with the rest of the African continent, North Africa has provided limited genomic data. Nonetheless, the genetic data available show a complex demographic scenario characterized by extensive admixture and drift. Despite the continuous gene flow from the Middle East, Europe and sub-Saharan Africa, an autochthonous genetic component that dates back to pre-Holocene times is still present in North African groups. The comparison of ancient and modern genomes has evidenced a genetic continuity in the region since Epipaleolithic times. Later population movements, especially the gene flow from the Middle East associated with the Neolithic, have diluted the genetic autochthonous component, creating an east to west gradient. Recent historical movements, such as the Arabization, have also contributed to the genetic landscape observed currently in North Africa and have culturally transformed the region. Genome analyses have not shown evidence of a clear correlation between cultural and genetic diversity in North Africa, as there is no genetic pattern of differentiation between Tamazight (i.e. Berber) and Arab speakers as a whole. Besides the gene flow received from neighboring areas, the analysis of North African genomes has shown that the region has also acted as a source of gene flow since ancient times. As a result of the genetic uniqueness of North African groups and the lack of available data, there is an urgent need for the study of genetic variation in the region and its implications in health and disease.
Asunto(s)
Árabes/genética , ADN/historia , Genética de Población/métodos , Pueblos Indígenas/genética , África del Norte/etnología , Flujo Génico , Historia Antigua , Humanos , Medio Oriente , FilogeografíaRESUMEN
To bypass a diverse range of fork stalling impediments encountered during genome replication, cells possess a variety of DNA damage tolerance (DDT) mechanisms including translesion synthesis, template switching, and fork reversal. These pathways function to bypass obstacles and allow efficient DNA synthesis to be maintained. In addition, lagging strand obstacles can also be circumvented by downstream priming during Okazaki fragment generation, leaving gaps to be filled post-replication. Whether repriming occurs on the leading strand has been intensely debated over the past half-century. Early studies indicated that both DNA strands were synthesised discontinuously. Although later studies suggested that leading strand synthesis was continuous, leading to the preferred semi-discontinuous replication model. However, more recently it has been established that replicative primases can perform leading strand repriming in prokaryotes. An analogous fork restart mechanism has also been identified in most eukaryotes, which possess a specialist primase called PrimPol that conducts repriming downstream of stalling lesions and structures. PrimPol also plays a more general role in maintaining efficient fork progression. Here, we review and discuss the historical evidence and recent discoveries that substantiate repriming as an intrinsic replication restart pathway for maintaining efficient genome duplication across all domains of life.
Asunto(s)
Replicación del ADN , ADN/biosíntesis , Animales , ADN/historia , Daño del ADN , ADN Primasa/clasificación , ADN Primasa/fisiología , ADN Polimerasa Dirigida por ADN/fisiología , Genoma , Historia del Siglo XX , Modelos Genéticos , Estrés Fisiológico/genéticaRESUMEN
The past 4 decades have seen remarkable advances in our understanding of the structural basis of gene regulation. Technological advances in protein expression, nucleic acid synthesis, and structural biology made it possible to study the proteins that regulate transcription in the context of ever larger complexes containing proteins bound to DNA. This review, written on the occasion of the 50th anniversary of the founding of the Protein Data Bank focuses on the insights gained from structural studies of protein-DNA complexes and the role the PDB has played in driving this research. I cover highlights in the field, beginning with X-ray crystal structures of the first DNA-binding domains to be studied, through recent cryo-EM structures of transcription factor binding to nucleosomal DNA.
Asunto(s)
ADN/metabolismo , Bases de Datos de Proteínas/historia , Regulación de la Expresión Génica , Biología Molecular/historia , Transcripción Genética , Animales , ADN/historia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Unión Proteica , Conformación ProteicaRESUMEN
Research involving ancient DNA (aDNA) has experienced a true technological revolution in recent years through advances in the recovery of aDNA and, particularly, through applications of high-throughput sequencing. Formerly restricted to the analysis of only limited amounts of genetic information, aDNA studies have now progressed to whole-genome sequencing for an increasing number of ancient individuals and extinct species, as well as to epigenomic characterization. Such advances have enabled the sequencing of specimens of up to 1 million years old, which, owing to their extensive DNA damage and contamination, were previously not amenable to genetic analyses. In this Review, we discuss these varied technical challenges and solutions for sequencing ancient genomes and epigenomes.
Asunto(s)
ADN/genética , ADN/historia , Epigenómica/métodos , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Animales , Epigenómica/tendencias , Genómica/tendencias , Secuenciación de Nucleótidos de Alto Rendimiento/tendencias , Historia Antigua , HumanosAsunto(s)
Carbón Mineral/historia , ADN/química , ADN/historia , Virología/historia , Difracción de Rayos X/historia , Carbón Orgánico/química , Carbón Orgánico/historia , Grafito/química , Grafito/historia , Historia del Siglo XX , Humanos , Poliovirus/química , Dispositivos de Protección Respiratoria/historia , Virus del Mosaico del Tabaco/químicaAsunto(s)
Ética en Investigación , Publicaciones Periódicas como Asunto/historia , Publicaciones Periódicas como Asunto/normas , Investigación/historia , Investigación/tendencias , Animales , Aniversarios y Eventos Especiales , Astronomía/historia , Autoria , ADN/química , ADN/historia , Ética en Investigación/historia , Fósiles , Calentamiento Global/legislación & jurisprudencia , Calentamiento Global/prevención & control , Calentamiento Global/estadística & datos numéricos , Procesos de Grupo , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Hominidae , Proyecto Genoma Humano/historia , Humanos , Cooperación Internacional , Ozono/análisis , Ozono/historia , Paleontología/historia , Revisión de la Investigación por Pares , Publicaciones Periódicas como Asunto/tendencias , Física/historia , Reproducibilidad de los Resultados , Investigación/educación , Investigación/normasRESUMEN
In 1869, Johann Friedrich Miescher discovered a new substance in the nucleus of living cells. The substance, which he called nuclein, is now known as DNA, yet both Miescher's name and his theoretical ideas about nuclein are all but forgotten. This paper traces the trajectory of Miescher's reception in the historiography of genetics. To his critics, Miescher was a "contaminator," whose preparations were impure. Modern historians portrayed him as a "confuser," whose misunderstandings delayed the development of molecular biology. Each of these portrayals reflects the disciplinary context in which Miescher's work was evaluated. Using archival sources to unearth Miescher's unpublished speculations-including an analogy between the hereditary material and language, and a speculation that a series of asymmetric carbon atoms could account for hereditary variation-this paper clarifies the ways in which the past was judged through the lens of contemporary concerns. It also shows how organization, structure, function, and information were already being considered when nuclein was first discovered nearly 150 years ago.
Asunto(s)
ADN/historia , Genética/historia , Historiografía , Biología Molecular/historia , Química/historia , Cromatina/aislamiento & purificación , ADN/aislamiento & purificación , Historia del Siglo XIX , Humanos , Relaciones Interprofesionales , Supuración/historia , SuizaRESUMEN
This speculative Essay explores the consequences of the imagined premature death of Oswald Avery, who in 1944 provided evidence that genes are made of DNA. Four imaginary alternate routes to the genetic function of DNA are outlined, each of which highlights different aspects of the actual process of discovery.
Asunto(s)
ADN/historia , Genes , Historia del Siglo XX , HumanosRESUMEN
Genetic information contains a record of the history of our species, and technological advances have transformed our ability to access this record. Many studies have used genome-wide data from populations today to learn about the peopling of the globe and subsequent adaptation to local conditions. Implicit in this research is the assumption that the geographic locations of people today are informative about the geographic locations of their ancestors in the distant past. However, it is now clear that long-range migration, admixture, and population replacement subsequent to the initial out-of-Africa expansion have altered the genetic structure of most of the world's human populations. In light of this we argue that it is time to critically reevaluate current models of the peopling of the globe, as well as the importance of natural selection in determining the geographic distribution of phenotypes. We specifically highlight the transformative potential of ancient DNA. By accessing the genetic make-up of populations living at archaeologically known times and places, ancient DNA makes it possible to directly track migrations and responses to natural selection.
Asunto(s)
ADN/genética , ADN/historia , Genética de Población , Genoma Humano , Geografía , Selección Genética/genética , África , Evolución Molecular , Historia Antigua , Humanos , FenotipoRESUMEN
Modern domestic plants and animals are subject to human-driven selection for desired phenotypic traits and behavior. Large-scale genetic studies of modern domestic populations and their wild relatives have revealed not only the genetic mechanisms underlying specific phenotypic traits, but also allowed for the identification of candidate domestication genes. Our understanding of the importance of these genes during the initial stages of the domestication process traditionally rests on the assumption that robust inferences about the past can be made on the basis of modern genetic datasets. A growing body of evidence from ancient DNA studies, however, has revealed that ancient and even historic populations often bear little resemblance to their modern counterparts. Here, we test the temporal context of selection on specific genetic loci known to differentiate modern domestic chickens from their extant wild ancestors. We extracted DNA from 80 ancient chickens excavated from 12 European archaeological sites, dated from â¼ 280 B.C. to the 18th century A.D. We targeted three unlinked genetic loci: the mitochondrial control region, a gene associated with yellow skin color (ß-carotene dioxygenase 2), and a putative domestication gene thought to be linked to photoperiod and reproduction (thyroid-stimulating hormone receptor, TSHR). Our results reveal significant variability in both nuclear genes, suggesting that the commonality of yellow skin in Western breeds and the near fixation of TSHR in all modern chickens took place only in the past 500 y. In addition, mitochondrial variation has increased as a result of recent admixture with exotic breeds. We conclude by emphasizing the perils of inferring the past from modern genetic data alone.