Recent human adaptation: genomic approaches, interpretation and insights.
Ontology highlight
ABSTRACT:
SUBMITTER: Scheinfeldt LB
PROVIDER: S-EPMC4882605 | biostudies-literature | 2013 Oct
REPOSITORIES: biostudies-literature
Publications
Recent human adaptation: genomic approaches, interpretation and insights.
Scheinfeldt Laura B LB Tishkoff Sarah A SA
Nature reviews. Genetics 20131001 10
The recent availability of genomic data has spurred many genome-wide studies of human adaptation in different populations worldwide. Such studies have provided insights into novel candidate genes and pathways that are putatively involved in adaptation to different environments, diets and disease prevalence. However, much work is needed to translate these results into candidate adaptive variants that are biologically interpretable. In this Review, we discuss methods that may help to identify true ...[more]
Similar Datasets
Project description:Glioblastoma (WHO grade IV astrocytoma) is the most frequent primary brain tumor in adults, representing a highly heterogeneous group of neoplasms that are among the most aggressive and challenging cancers to treat. An improved understanding of the molecular pathways that drive malignancy in glioblastoma has led to the development of various biomarkers and the evaluation of several agents specifically targeting tumor cells and the tumor microenvironment. A number of rational approaches are being investigated, including therapies targeting tumor growth factor receptors and downstream pathways, cell cycle and epigenetic regulation, angiogenesis and antitumor immune response. Moreover, recent identification and validation of prognostic and predictive biomarkers have allowed implementation of modern trial designs based on matching molecular features of tumors to targeted therapeutics. However, while occasional targeted therapy responses have been documented in patients, to date no targeted therapy has been formally validated as effective in clinical trials. The lack of knowledge about relevant molecular drivers in vivo combined with a lack of highly bioactive and brain penetrant-targeted therapies remain significant challenges. In this article, we review the most promising biological insights that have opened the way for the development of targeted therapies in glioblastoma, and examine recent data from clinical trials evaluating targeted therapies and immunotherapies. We discuss challenges and opportunities for the development of these agents in glioblastoma.
| S-EPMC5834086 | biostudies-literature
Project description:Recent human adaptations have shaped population differentiation in genomic regions containing putative functional variants, mostly located in predicted regulatory elements. However, their actual functionalities and the underlying mechanism of recent adaptation remain poorly understood. In the current study, regions of genes and repeats were investigated for functionality depending on the degree of population differentiation, FST or ΔDAF (a difference in derived allele frequency). The high FST in the 5´ or 3´ untranslated regions (UTRs), in particular, confirmed that population differences arose mainly from differences in regulation. Expression quantitative trait loci (eQTL) analyses using lymphoblastoid cell lines indicated that the majority of the highly population-specific regions represented cis- and/or trans-eQTL. However, groups having the highest ΔDAFs did not necessarily have higher proportions of eQTL variants; in these groups, the patterns were complex, indicating recent intricate adaptations. The results indicated that East Asian (EAS) and European populations (EUR) experienced mutual selection pressures. The mean derived allele frequency of the high ΔDAF groups suggested that EAS and EUR underwent strong adaptation; however, the African population in Africa (AFR) experienced slight, yet broad, adaptation. The DAF distributions of variants in the gene regions showed clear selective pressure in each population, which implies the existence of more recent regulatory adaptations in cells other than lymphoblastoid cell lines. In-depth analysis of population-differentiated regions indicated that the coding gene, RNF135, represented a trans-regulation hotspot via cis-regulation by the population-specific variants in the region of selective sweep. Together, the results provide strong evidence of actual intricate adaptation of human populations via regulatory manipulation.
| S-EPMC5167553 | biostudies-literature
Project description:Prickles act against herbivores, pathogens or mechanical injury, while also preventing water loss. However, whether prickles have new function and the molecular genetics of prickle patterning remain poorly explored. Here, we generated a high-quality reference genome assembly for 'Basye's Thornless' (BT), a prickle-free cultivar of Rosa wichuraiana, to identify genetic elements related to stem prickle development. The BT genome harbors a high level of sequence diversity in itself and with cultivar 'Old Blush' (R. chinensis), a founder genotype in rose domestication. Inheritance of stem prickle density was determined and two QTL were identified. Differentially expressed genes in QTL were involved in water-related functions, suggesting that prickle density may hitchhike with adaptations to moist environments. While the prickle-related gene-regulatory-network (GRN) was highly conserved, the expression variation of key candidate genes was associated with prickle density. Our study provides fundamental resources and insights for genome evolution in the Rosaceae. Ongoing efforts on identification of the molecular bases for key rose traits may lead to improvements for horticultural markets.
| S-EPMC8694671 | biostudies-literature
Project description:BackgroundPenicillium chrysogenum is a filamentous fungal species with diverse habitats, yet little is known about its genetics in adapting to extreme subseafloor sedimental environments.ResultsHere, we report the discovery of P. chrysogenum strain 28R-6-F01, isolated from deep coal-bearing sediments 2306 m beneath the seafloor. This strain possesses exceptional characteristics, including the ability to thrive in extreme conditions such as high temperature (45 °C), high pressure (35 Mpa), and anaerobic environments, and exhibits broad-spectrum antimicrobial activity, producing the antibiotic penicillin at a concentration of 358 μg/mL. Genome sequencing and assembly revealed a genome size of 33.19 Mb with a GC content of 48.84%, containing 6959 coding genes. Comparative analysis with eight terrestrial strains identified 88 unique genes primarily associated with penicillin and aflatoxins biosynthesis, carbohydrate degradation, viral resistance, and three secondary metabolism gene clusters. Furthermore, significant expansions in gene families related to DNA repair were observed, likely linked to the strain's adaptation to its environmental niche.ConclusionsOur findings provide insights into the genomic and biological characteristics of P. chrysogenum adaptation to extreme anaerobic subseafloor sedimentary environments, such as high temperature and pressure.
| S-EPMC10759354 | biostudies-literature
Project description:BackgroundRapid adaptation to new environments can facilitate species invasions and range expansions. Understanding the mechanisms of adaptation used by invasive disease vectors in new regions has key implications for mitigating the prevalence and spread of vector-borne disease, although they remain relatively unexplored.ResultsHere, we integrate whole-genome sequencing data from 96 Aedes aegypti mosquitoes collected from various sites in southern and central California with 25 annual topo-climate variables to investigate genome-wide signals of local adaptation among populations. Patterns of population structure, as inferred using principal components and admixture analysis, were consistent with three genetic clusters. Using various landscape genomics approaches, which all remove the confounding effects of shared ancestry on correlations between genetic and environmental variation, we identified 112 genes showing strong signals of local environmental adaptation associated with one or more topo-climate factors. Some of them have known effects in climate adaptation, such as heat-shock proteins, which shows selective sweep and recent positive selection acting on these genomic regions.ConclusionsOur results provide a genome wide perspective on the distribution of adaptive loci and lay the foundation for future work to understand how environmental adaptation in Ae. aegypti impacts the arboviral disease landscape and how such adaptation could help or hinder efforts at population control.
| S-EPMC10257851 | biostudies-literature
Project description:Cell subtype proportion variability between samples contributes significantly to the variation of functional genomic properties such as gene expression or DNA methylation. Although the impact of the variation of cell subtype composition on measured genomic quantities is recognized, and some innovative tools have been developed for the analysis of heterogeneous samples, most functional genomics studies using samples with mixed cell types still ignore the influence of cell subtype proportion variation, or just deal with it as a nuisance variable to be eliminated. Here we demonstrate how harvesting information about cell subtype proportions from functional genomics data can provide insights into cellular changes associated with phenotypes. We focused on two types of mixed cell populations, human blood and mouse kidney. Cell type prediction is well developed in the former, but not currently in the latter. Estimating the cellular repertoire is easier when a reference dataset from purified samples of all cell types in the tissue is available, as is the case for blood. However, reference datasets are not available for most other tissues, such as the kidney. In this study, we showed that the proportion of alterations attributable to changes in the cellular composition varies strikingly in the two disorders (asthma and systemic lupus erythematosus), suggesting that the contribution of cell subtype proportion changes to functional genomic properties can be disease-specific. We also showed that a reference dataset from a single-cell RNA-seq study successfully estimated the cell subtype proportions in mouse kidney and allowed us to distinguish altered cell subtype differences between two different knock-out mouse models, both of which had reported a reduced number of glomeruli compared to their wild-type counterparts. These findings demonstrate that testing for changes in cell subtype proportions between conditions can yield important insights in functional genomics studies.
| S-EPMC6483354 | biostudies-literature
Project description:Elongation of RNA polymerase II (Pol II) is affected by many factors including DNA damage. Bulky damage, such as lesions caused by ultraviolet (UV) radiation, arrests Pol II and inhibits gene transcription, and may lead to genome instability and cell death. Cells activate transcription-coupled nucleotide excision repair (TC-NER) to remove Pol II-impeding damage and allow transcription resumption. TC-NER initiation in humans is mediated by Cockayne syndrome group B (CSB) protein, which binds to the stalled Pol II and promotes assembly of the repair machinery. Given the complex nature of the TC-NER pathway and its unique function at the interface between transcription and repair, new approaches are required to gain in-depth understanding of the mechanism. Advances in genomic approaches provide an important opportunity to investigate how TC-NER is initiated upon damage-induced Pol II stalling and what factors are involved in this process. In this Review, we discuss new mechanisms of TC-NER revealed by genome-wide DNA damage mapping and new TC-NER factors identified by high-throughput screening. As TC-NER conducts strand-specific repair of mutagenic damage, we also discuss how this repair pathway causes mutational strand asymmetry in the cancer genome.
| S-EPMC8205993 | biostudies-literature
Project description:Pneumocystis jirovecii, the fungal agent of human Pneumocystis pneumonia, is closely related to macaque Pneumocystis. Little is known about other Pneumocystis species in distantly related mammals, none of which are capable of establishing infection in humans. The molecular basis of host specificity in Pneumocystis remains unknown as experiments are limited due to an inability to culture any species in vitro. To explore Pneumocystis evolutionary adaptations, we have sequenced the genomes of species infecting macaques, rabbits, dogs and rats and compared them to available genomes of species infecting humans, mice and rats. Complete whole genome sequence data enables analysis and robust phylogeny, identification of important genetic features of the host adaptation, and estimation of speciation timing relative to the rise of their mammalian hosts. Our data reveals insights into the evolution of P. jirovecii, the sole member of the genus able to infect humans.
| S-EPMC7940399 | biostudies-literature
Project description:The osmotolerant Zygosaccharomyces rouxii is known for its trait to survive in extreme high sugar environments. This ability determines its role in the fermentation process and leads to yeast spoilage in the food industry. However, our knowledge of the gene expression in response to high sugar stress remains limited. Here, we conducted RNA-sequencing (RNA-seq) under different sugar concentrations of the spoilage yeast, Z. rouxii, which exhibit extremely high tolerance to sugar stress. The obtained differentially expressed genes (DEGs) are significantly different to that of the Saccharomyces cerevisiae, which is sensitive to extreme high sugar stress. Most of the DEGs participated in the "glucan synthesis," "transmembrane transport," "ribosome," etc. In this work, we also demonstrated that the gene ZYRO0B03476g (ZrKAR2) encoding Kar2p can significantly affect the growth of Z. rouxii under high sugar stress. In addition, we combined with a previous study on the genome sequence of Z. rouxii, indicating that several gene families contain significantly more gene copies in the Z. rouxii lineage, which involved in tolerance to sugar stress. Our results provide a gene insight for understanding the high sugar tolerance trait, which may impact food and biotechnological industries and improve the osmotolerance in other organisms.
| S-EPMC7026193 | biostudies-literature
Project description:Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens.
| S-EPMC10823079 | biostudies-literature