The Drosophila gene conventionally called for, encoding a cGMP-dependent protein kinase. Natural rover and sitter variants illustrate the distinction between identifying a behavioural mechanism and explaining the historical maintenance of its variants.
A reagent adding a predefined three-nucleotide unit during oligonucleotide synthesis. Mixtures of whole codons allow controlled amino-acid representation while avoiding unwanted stop codons.[ref]
A collection of DNA molecules representing different sequences. For directed evolution, accessible diversity, sequence frequencies and linkage to the measured phenotype matter more than nominal molecule count.
The fraction or distribution of intended variants actually constructed or sampled, with those two meanings distinguished. Unequal variant frequencies and repeated clones reduce effective exploration.
Deliberate or naturally induced generation of sequence changes. In experimental protein evolution the method determines the distribution of variants available for testing.
The number or distribution of sequence changes per variant in a mutagenized library. Higher load explores more distant combinations while commonly reducing functional recovery.
Diversification of specified sequence positions across a defined set of residues. It focuses screening but can exclude important effects at unchosen sites.
Insertion of a copied mobile element through an RNA intermediate. Orthologous insertion patterns can inform phylogenetic relationships, with lineage sorting and insertion-site properties considered.
A genomic region showing exceptionally strong sequence conservation across the compared lineages. Conserved cores can anchor sequence capture, while associated variable regions contribute phylogenetic information.
Measurement and comparison of expressed transcripts. Comparative developmental studies require control of stage, tissue composition, gene correspondence and biological replication.
Measurement of gene expression together with positions within a tissue. Its spatial units can be individual molecules, segmented cells or capture regions; these units should not be conflated.
Relationship between corresponding genes separated by lineage divergence, distinguished from relationships created by gene duplication. Correct copy assignment matters when interpreting comparative expression or inferring a gene tree.
The number of somatic mutations per defined amount of tumour sequence under a specified assay. It is an imperfect proxy for the number of useful immunogenic targets.
The ratio of nonsynonymous to synonymous substitution rates after accounting for relevant mutation opportunities. Somatic-cancer analyses need background models appropriate to somatic mutation processes rather than raw event ratios.
A DNA position where cytosine is followed by guanine along one strand. Methylation and sequence context influence its mutational behaviour.
A controlled change to a genetic system used to test a functional hypothesis. Its interpretation depends on specificity, timing and controls for secondary effects.
Modification or design of a protein to change its properties. Rational design, library construction and directed evolution offer complementary ways to test sequence–function relationships.
Design of a protein catalyst using computational models of structure and chemistry. Experimental screening and directed evolution test and improve the proposed catalytic arrangement.
An unintended effect outside the nominated molecular target. Independent reagents, verified target changes and functional rescue help distinguish target-specific consequences from these effects.
A genetic intervention eliminating functional output of a gene. A targeted insertion or deletion is not by itself proof of knockout: remaining alleles, reading frame and functional protein must be checked.
Targeted alteration of a genome using a guide-directed CRISPR system. Independent targeting reagents, verification of the resulting alleles and functional rescue help distinguish an intended effect from unrelated damage.
Sequence-targeted fluorescent localization of chromosomal sites using a nuclease-inactive targeting system. Colocalization with a protein is evidence of shared location, not necessarily direct molecular contact.
A guide-directed bacterial DNA-recognition and cleavage system. Catalytically inactive dCas9 retains targeting functions used in imaging and transcriptional regulation.
Guide-directed recruitment of transcriptional activation machinery to increase endogenous gene expression. Unlike a promoter-replacing knock-in, it need not change the target sequence.
Guide-directed reduction of gene expression using nuclease-inactive DNA targeting. In mammalian cells, dCas9 fused to a repressor can reduce transcription without requiring a DNA break.
A guide-directed DNA nuclease. Target recognition depends on a guide RNA and an appropriate protospacer adjacent motif; cleavage is followed by cellular repair, so cleavage alone does not specify the final allele.
A catalytically inactive form of Cas9 retaining guide-directed DNA binding. Recruitment of regulatory domains makes it a platform for CRISPR interference and CRISPR activation.
A short target-adjacent DNA motif recognized by a CRISPR-associated nuclease. The motif requirement depends on the nuclease; the commonly used Cas9 from Streptococcus pyogenes recognizes NGG.
An RNA molecule whose complementary sequence directs a targeting complex to a nucleic-acid sequence. In CRISPR genome editing, guide complementarity and a compatible protospacer adjacent motif jointly constrain targeting.
Optogenetics uses genetically introduced light-responsive components to perturb or monitor biological processes with spatial and temporal control. Light-only, construct-only and expression-matched controls help distinguish the intended response from phototoxicity.
site-directed mutagenesis deliberately changes a specified sequence position. Functional interpretation requires distinguishing a local mechanistic effect from altered abundance, localization or protein folding.
Origin of a new coding gene from ancestrally non-coding DNA, rather than divergence from a previously coding copy. Failure to detect a distant relative is insufficient evidence: comparative genomic context and evidence of ancestral coding status matter.
Acquisition of a new function by a gene copy, classically following gene duplication. The other copy can retain an ancestral function while changes accumulate in the retained duplicate.
Partitioning of ancestral functions or expression domains between duplicated genes. Each copy can retain a subset of deployments that a single ancestral copy performed.
Creation of an additional inherited copy of a gene. Copies can be lost, retain shared functions, undergo subfunctionalization, or undergo neofunctionalization; duplication alone does not guarantee a useful novelty.
Duplication of the full genomic complement. gene loss, subfunctionalization and neofunctionalization can obscure the original duplicated organization.
The hypothesis that two early large-scale duplication rounds contributed to the multiple paralogous genomic regions of jawed vertebrates. Hox clusters are one informative set of loci; a single family does not by itself establish genome-wide duplication.
Creation of adjacent copies of a gene or genomic segment. Subsequent divergence can produce a local gene family while preserving aspects of ancestral order.
Gene-family evolution through duplication and retention of some copies and loss or pseudogenization of others.
A relationship between genes arising through duplication. It differs from orthology, which concerns divergence through lineage splitting.
A gene related to another through duplication. Comparing paralogues as if they were orthologues can mislead inference about lineage-specific sequence change.
Covalent methyl-group modification of DNA, involved in regulation and cellular memory. Its relationship to transcription depends on genomic location and biological context.
Methylation in an asymmetric CHH sequence context, where H is A, C or T; maintenance of the pattern requires repeated targeting rather than direct copying from a symmetric dyad.
Methylation in the CHG sequence context, where H is A, C or T; its restoration is strongly coupled to H3K9 methylation.
Establishment of methylation at a site that lacks the previous methylation pattern; sequence-directed and chromatin-directed recruitment provide specificity.
Loss of methylated cytosines through active enzymatic replacement or through failed maintenance during replication.
A plant DNA glycosylase involved in reproductive epigenetic reprogramming and maternal imprinting effects.
A plant DNA glycosylase/lyase involved in active DNA demethylation through a repair-associated pathway.
A methyltransferase recruited by RNA-directed DNA methylation that can establish methylation in multiple cytosine sequence contexts.
A genomic interval with a statistically supported difference in DNA methylation between the compared samples.
A posterior methylation profile gives the posterior probability of DNA methylation at each modeled site. It differs from one sampled binary pattern and from a maximum-probability joint pattern.
Measurement of RNA profiles in individual cells. It resolves heterogeneous populations, but transcript abundance alone does not prove lineage potential, signalling dependence or new transcription.
An inferred ordering of molecular states along a developmental trajectory. It does not itself establish which cell divided to produce another cell.
An inferred ordering of biological cells by a model of state progression. It is not by itself a measured time, a lineage trace or proof of causal developmental transitions.
The complex of DNA and associated proteins that organises nuclear genetic material and helps regulate its accessibility.
Transcriptional repression mediated by Polycomb-group proteins and associated chromatin states. Developmental regulators can be kept inactive until appropriate activation.
The spatial arrangement and dynamic interactions of chromatin. Hi-C, imaging and accessibility assays measure different aspects; no one readout establishes a universal three-dimensional structure.
A bacterial DNA-recognition pair marks an integrated operator array with a fluorescent repressor. It enables live tracking of a chosen genetic locus, while the array and bound protein can perturb that locus.
A nuclear volume preferentially occupied by a chromosome. Territories can contact and intermingle at their boundaries rather than forming sealed compartments.
A genomic interaction pattern in which regions with related properties preferentially associate. Large-scale compartments and cohesin-dependent loop domains can respond differently to perturbation.
An organization in which separated genomic regions are brought into enhanced proximity. Contact enrichment and a fixed loop in every biological cell are different claims.
A mechanism in which a molecular complex progressively enlarges a DNA loop. Its predictions can be tested through contact maps and acute perturbation of architectural factors.
A genomic interval with preferential internal contact frequency under a specified analysis. Its boundaries and physical realization can vary between biological cells and conditions.
Crosslinking, fragmentation and ligation methods that infer genomic proximity from recovered junctions. Contact frequency is not automatically an absolute spatial distance or proof of direct functional interaction.
A genome-wide chromosome-contact assay. Coverage, fragment recovery and bin size affect interpretable resolution; the matrix describes sampled contacts rather than a single universal chromosome structure.
A succession of nucleosomes connected by linker DNA. Regular arrays reconstituted under selected conditions need not represent one universal cellular fibre architecture.
The propensity of a chromatin region to be reached by a specified probe or enzyme under stated conditions. Accessibility, transcription-factor occupancy and regulatory function are related but distinct.
Sequencing-based mapping of DNA cleavage by DNase, used to identify accessible regions and hypersensitive sites. Sequence preferences and digestion conditions require controls.
Profiling accessible DNA through transposase-mediated adapter insertion and sequencing. Enzyme bias, sample preparation and biological cell composition affect the observed accessibility landscape.
A dinoflagellate histone-like protein in the HU-related families is distinct from a canonical eukaryotic core histone. Its distribution is lineage dependent; the label must not be used to imply restoration of a conventional nucleosomal genome.
A dinoflagellate viral nucleoprotein is a member of the DVNP family of basic nuclear proteins found in dinoflagellates and related large DNA viruses. Comparative abundance and yeast perturbation experiments support interactions with DNA packaging, without fully reconstructing the evolutionary transition.
Liquid-crystalline chromosome organization describes ordered dense DNA packing with orientational organization distinct from a conventional nucleosome array. Microscopic order does not by itself identify the proteins or interactions required to maintain it.
A region or activity limiting propagation of a chromatin state. A functional boundary is demonstrated by perturbing it and measuring the resulting domain behavior, rather than merely observing an endpoint.
A relatively inaccessible, frequently repressive form of chromatin. Different forms have distinct marks and mechanisms; H3K9 methylation is a major example rather than a universal definition.
Methylation of lysine 9 of histone H3. Different methylation states can recruit specific reader proteins and contribute to heterochromatin regulation.
Extension of a repressive chromatin domain beyond its initial nucleation site. Reader–writer positive feedback can propagate local marks, while histone turnover, opposing activities and chromatin boundaries constrain the domain.
Alteration of nucleosome organization, positioning or composition by associated machinery. Increased accessibility does not by itself identify the direct molecular target of a drug.
An ATP-dependent chromatin remodelling complex uses ATP-dependent activity to alter nucleosome positioning, composition or organization. It changes access to DNA without needing to change the DNA sequence.
Addition of acetyl groups to histones. Its functional effects depend on the site, associated readers and local chromatin context.
A repeating chromatin unit in which DNA wraps around a histone core. Position, turnover and modification affect accessibility of the associated DNA.
Movement of histones from one DNA substrate or complex to another. In competition experiments, loss of histones from a labelled complex need not release free DNA if another DNA-binding protein remains attached.
Resistance of a histone–DNA particle to loss or rearrangement of its components under specified conditions. Competitor-induced histone transfer can reveal destabilization even while a DNA-binding protein remains attached.
Transient local unwrapping and rewrapping of nucleosomal DNA. This changes the accessibility of DNA and histone surfaces without requiring complete and irreversible loss of the histone octamer.
DNA connecting adjacent nucleosome cores. Its length and accessibility affect nucleosome-array organization.
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Molecular genetics is a branch of genetics that focuses on the molecular structure and function of genes. It combines principles from molecular biology, biochemistry, and genetics to study the role of genes in heredity, variation, and the mechanisms of genetic expression and regulation. Key areas of molecular genetics include: 1. **Gene Structure and Function**: Understanding how genes are organized, including their sequence, regulation, and the production of RNA and proteins.