Academic journal article The Science Teacher. Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the genome, chromosomes, genes, a gene locus, and alleles. In this simple activity following the 5E approach Bybee et al. This activity should come after students have been taught DNA structure, including complementary base pairs Adenine-Thymine; Guanine-Cytosine.
Teytelman, L. Therefore, through Girl smoke fetish 3D structures generated by Hierarchical3DGenome researchers can study the relationship between chromosomal regions at a fine-grained scale. The position of a bead is then represented by three coordinates x, Chromosomes models, z. Figure 6. FEBS letters Fourthly, we investigated if the high resolution chromosomal models were consistent with the FISH data 8. Williamson, I. Rieber, L. Methods 58 3— Chromosomes models, the structure sampling is much Cjromosomes intensive since the number of chromosomal fragments to be modeled is much larger in high resolution.
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In the multiple stand models the chromosome is supposed to consist of several DNA-protein strands. The models are: 1. The various chromosome models may be grouped under two heads: Multiple strand models and single strand models. The diagrammatic representation of the folded fibre model is given in the Fig. In effect, the DNA molecules are kept in position by the protein-linkers. This is a question and Asian angels sex forum for students, teachers and general visitors Chromosomes models exchanging articles, answers and notes. Single Strand Models Various studies have demonstrated that chromosomes are single stranded. The email has already been used, in case you have forgotten the password click here. Nucleic Acids: Chromosomes models and Structure Macromolecules. The Freese-Taylor model.
The following points highlight the top four models proposed for chromosome structure.
- The various chromosomes models may be grouped under two head: multiple strand models and single strand models.
- The following points highlight the top two models of chromosomes.
- The following points highlight the top four models proposed for chromosome structure.
The following points highlight the top four models proposed for chromosome structure. The models are: 1. Molecular Model 2. General Chromosome Model 4. Folded Fibre Model. This model of chromosome structure was proposed by Taylor and coworkers in , and is based on the semiconservative replication of eukaryotic chromosome.
According to this model, the chromatid consists of only one DNA chain, where several DNA double helices linked end-to-end by protein molecules. Interactions of protein molecules with each other are responsible for coiling and uncoiling of the chromosomes.
DNA molecule can be broken by deoxyribonucleases but not by proteolytic enzymes. This model was put forth by Ris in and Ris and Chandler in According to this model, the chromosome is multi-stranded, i. The diameter of the DNA double helix is 2 nm, and two DNA molecules are associated with protein to make the chromatin fibre.
Diameters of chromatin fibres, quarter chromatids, half chromatids and chromatids are 10 nm, 40 nm, 80 nm, and nm, respectively. However, according to the recent studies, the chromosome is definitely not multi-stranded. This model was proposed by Crick in ; it suggests that DNA in a chromatid is a large monomer which runs continuously from one end to the other.
Band and inter band regions of chromosomes especially giant chromosomes are suggested to have distinct functions. DuPraw in proposed this model on the basis of electron microscopic studies of human chromosomes.
According to this model, each chromatid contains single long nucleoprotein complex Chromatin fibres in which a single DNA double helix forms the main structure of the axis. This model of chromosome has been widely accepted. Thus each metaphase chromatid is composed of tightly folded single chromatin fibre of A diameter. The exact 3-dimensional configuration of nucleoprotein fibre in any given chromatid is not constant. This configuration varies from metaphase to interphase. It also differs for the same chromosome during mitosis and meiosis, in mature sperm, and from metaphase to metaphase.
Non-homologous chromosomes differ not only in their genetic content but also in their 3-dimensional configurations.
This model suggests that in the centromeric region, chromatin fibres are continuous and pass from one arm to the other for each sister chromatid; the sister chromatids are held closely together in this region up to the beginning of their separation during anaphase.
This model also suggests that a small amount of DNA is synthesized before the sister chromatids actually separate. The diagrammatic representation of the folded fibre model is given in the Fig. The A type fibre is intermediate between the extended DNA double helix and the fully packed B type fibre.
DNA double helix is 20 A in diameter; it associates with histones to form a nucleohistone fibril. Top Menu BiologyDiscussion. Autoriploidy: Fertility and Phenotypic Effects. Nucleic Acids: Meaning and Structure Macromolecules. This is a question and answer forum for students, teachers and general visitors for exchanging articles, answers and notes.
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Top Menu BiologyDiscussion. Taylor postulated that the chromosomes consist of a long protein backbone from which DNA coils branch off just like the legs of a centipede. Most of the evidences now indicate that chromosomes are not multi- stranded. Top Menu BiologyDiscussion. The email has already been used, in case you have forgotten the password click here. According to this model the chromosome consists of 64 double helices of DNA arranged in a parallel manner, and twisted together like the strands of a rope.
Chromosomes models. Multiple Strand Models
Fibrils ranging from 30 to A, and even A, have been seen by various electron microscopists during interphase and mitosis. In the multiple stand models the chromosome is supposed to consist of several DNA-protein strands. Simple multi-stranded model. According to this model the chromosome consists of 64 double helices of DNA arranged in a parallel manner, and twisted together like the strands of a rope. The difficulty with this model is that replication of DNA would involve a large amount of untwisting and untangling.
Two 40A nucleoprotein fibrils make up a A fibril called elementary chromosome fibril. Single Strand Models Various studies have demonstrated that chromosomes are single stranded. These studies include the stretching of lamp brush chromosomes and action of enzymes on their structure. Taylor postulated that the chromosomes consist of a long protein backbone from which DNA coils branch off just like the legs of a centipede.
The Freese-Taylor model. According to this model there are two protein spines instead of one. The DNA chains stretch between them like the steps of a ladder. In effect the DNA molecules are kept in position by the protein linkers.
Coiled coil model. According to Nebel and others the chromosome is made up of only a single fibril. This fibril is tightly coiled and the coil is thrown into secondary coils. Ris suggested a modified model according to which the chromosome fibril is folded to form the chromosome. The following points highlight the top four models proposed for chromosome structure. The models are: 1. Molecular Model 2. General Chromosome Model 4. Folded Fibre Model. This model of chromosome structure was proposed by Taylor and coworkers in , and is based on the semiconservative replication of eukaryotic chromosome.
According to this model, the chromatid consists of only one DNA chain, where several DNA double helices linked end-to-end by protein molecules. Interactions of protein molecules with each other are responsible for coiling and uncoiling of the chromosomes. DNA molecule can be broken by deoxyribonucleases but not by proteolytic enzymes.
This model was put forth by Ris in and Ris and Chandler in According to this model, the chromosome is multi-stranded, i. The diameter of the DNA double helix is 2 nm, and two DNA molecules are associated with protein to make the chromatin fibre. Diameters of chromatin fibres, quarter chromatids, half chromatids and chromatids are 10 nm, 40 nm, 80 nm, and nm, respectively.
However, according to the recent studies, the chromosome is definitely not multi-stranded. This model was proposed by Crick in ; it suggests that DNA in a chromatid is a large monomer which runs continuously from one end to the other.
Band and inter band regions of chromosomes especially giant chromosomes are suggested to have distinct functions. DuPraw in proposed this model on the basis of electron microscopic studies of human chromosomes. According to this model, each chromatid contains single long nucleoprotein complex Chromatin fibres in which a single DNA double helix forms the main structure of the axis.
Help us improve our products. Sign up to take part. A Nature Research Journal. Eukaryotic chromosomes are often composed of components organized into multiple scales, such as nucleosomes, chromatin fibers, topologically associated domains TAD , chromosome compartments, and chromosome territories. Therefore, reconstructing detailed 3D models of chromosomes in high resolution is useful for advancing genome research. However, the task of constructing quality high-resolution 3D models is still challenging with existing methods.
The algorithm first reconstructs high-resolution 3D models at TAD level. The TAD models are then assembled to form complete high-resolution chromosomal models. The assembly of TAD models is guided by a complete low-resolution chromosome model. These high-resolution models satisfy Hi-C chromosomal contacts well and are consistent with models built at lower i. The architecture of chromosomes and genomes is important for cellular function 1 , 2 , 3. However, the principles governing the folding of chromosomes are still poorly understood.
The traditional microscopy technique - Fluorescent in Situ Hybridization FISH has been used to study chromosome architecture, but is limited by its low resolution and low throughput 4 , 5 , 6 , 7. Chromosome conformation capture 3C techniques like Hi-C 1 and TCC 2 can capture interactions between chromosomal fragments, and quantify the number of interaction frequencies IFs between them at a specific resolution. The bigger the interaction frequency between two fragments, the higher the probability that they are close in the three-dimensional 3D space.
The interaction frequencies between pairs of chromosomal fragments are often summarized as a symmetric matrix, called contact matrix or map. Contact matrices can be used to analyze the spatial organization of chromosomes or genomes. For instance, the chromosomal contact matrices have been used to confirm or identify the hallmarks of the human genome organization such as chromosome territories, chromosomal two-compartment partitions, chromatin loops, and topologically associated domains TAD 1 , 8 , 9.
Contact matrices can also be used to reconstruct 3D models of chromosomes and genomes to further facilitate the study of their organization. Various methods have been proposed to reconstruct 3D models of chromosomes or genomes 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , On one hand, some of these methods utilize a function that approximates the inverse relationship between interaction frequencies IFs and spatial distances between fragments and then uses the distances as restraints to build 3D models via spatial optimization.
These methods are called the optimization based method 10 , 14 , 17 , 24 , 25 , 26 , In the early work of Duan et al. On the other hand, some methods are designed to maximize the likelihood of a 3D model by using model-based methods that assumes that contact frequencies are related to distances via a probabilistic function.
These methods use for example the Markov Chain Monte Carlo sampling technique to reconstruct 3D chromosome models by satisfying as many converted Euclidian distances as possible 11 , 12 , 27 , Most of the existing methods are capable of reconstructing chromosome or genome models of low resolution e. They can also reconstruct the 3D models of a small region of a chromosome at a high resolution.
LorDG solves a non-convex optimization problem to obtain coordinates of loci so that it can generate different models corresponding with different local optimums. However, because LorDG put a high priority on satisfying contacts with high interaction frequencies, its models often satisfy a major set of contacts with high interaction frequencies and are similar to each other.
More recently, Rieber, L. This algorithm partitions a Hi-C dataset into subsets, performs high-resolution MDS separately on each subset, and then reassembles the partitions using low-resolution MDS. At the time of writing this manuscript, the miniMDS is the only known method that has attempted to build a relatively higher resolution 3D models of an entire chromosome. High-resolution genome structure modeling has several challenges.
Firstly, the structure sampling is much more intensive since the number of chromosomal fragments to be modeled is much larger in high resolution. Secondly, as the resolution increases, the number of contacts between fragments gets smaller, leaving less contact data for restraining the positions of the fragments.
Finally, the search space for high-resolution models is much larger than low-resolution models, making spatial optimization much more complicated. And due to the substantial increase of the model space, models with different topologies in high resolution may satisfy the same chromosomal data. One way to reduce the search space is to require that high-resolution models have a structural topology similar to that of low-resolution models whose structure can be more stably constructed due to the availability of more contact data between larger fragments.
Our results show that the high-resolution chromosome models reconstructed by our method satisfied input chromosomal contacts well, and are consistent with the experimental FISH data. In this work, we used two normalizations in two modelling processes. The first one is Knight—Ruiz normalization KR method 30 for building high resolution model of individual domains step 4 in Fig. The second one is iterative correction and eigenvector decomposition ICE normalization 31 method for building the low-resolution model of the entire chromosome step 2 in Fig.
The steps of Hierarchical3DGenome algorithm to reconstruct high-resolution models of chromosomes. The seven steps that Hierarchical3DGenome takes to reconstruct high-resolution models of chromosomes are: 1 break a chromosome into chromosomal domains according to input data and represent each domain as a point or bead, 2 build a 3D model of the entire chromosome at low resolution, 3 create a contact matrix for each domain, such that for n domains there are n contact matrices, 4 build 3D model of high resolution for each domain, 5 scale the 3D Models of the entire chromosome at low resolution to match with the models of the domains at high resolution, 6 substitute beads in low-resolution models with their high-resolution domain models, and 7 refine the high-resoluiton models of the entire chromosome to satisfy inter-domain contacts.
A chromosome is modeled as a string of beads in 3D space, where each bead denotes the midpoint of a DNA fragment at a specific resolution e. The position of a bead is then represented by three coordinates x, y, z. The goal is to place beads in 3D space so that their pairwise distances satisfy the expected distances converted from interaction frequencies as well as possible.
Our algorithm first reconstructs the 3D model of a chromosome at low resolution, which is used to guide the search for optimal models at high resolution.
Each fragment or point in low-resolution models represents a contact domain, which is considered a structural unit of chromosome 8. A chromosomal domain has substantially more contacts within itself than with other domains. Therefore, the accurate models of each chromosomal domain at high-resolution can be reconstructed individually. The models of individual domains are then assembled together according to the overall topology of full chromosomal models at low resolution. Specifically, our hierarchical algorithm, Hierarchical3DGenome, constructs high resolution chromosome 3D models in seven steps Fig.
The input is a contact matrix of a chromosome at a high-resolution e. In Step 1, the chromosome is partitioned into contact domains or topologically associated domains TADs using the arrowhead domain algorithm 8. When a domain contains small domains inside, only this domain is considered because the small domains have been represented by it. Then, each separate domain is represented by a point or bead and the interaction frequencies between beads are calculated to make a low-resolution contact matrix for the entire chromosome.
The matrix is normalized by the iterative correction and eigenvector decomposition ICE normalization 31 to remove technical biases 32 , biological factors 33 and the different visibility of beads due to their different lengths. This new contact matrix is used to build a low-resolution model of the entire chromosome using our in-house method LorDG 17 in Step 2.
We used the default parameter settings in LorDG. The default parameter setting for LorDG algorithm allows it to search for the best conversion factor within the range [0. The high-resolution contact matrices of individual domains are also extracted from the full high-resolution contact matrix of the chromosome in Step 3.
The topology of a correct high-resolution model of a chromosome should be similar to that of its correct low-resolution model, even though it is not guaranteed that they are in the same scale. So, in Step 5, the low-resolution model of the full chromosome constructed in Step 2 is scaled by a ratio so that it can be used to guide the assembly of the high-resolution models of individual domains into a final high-resolution model of the entire chromosome.
After the low-resolution model is scaled to match with the scale of high resolution, in Step 6, each bead of the low-resolution model is substituted by a high-resolution model constructed in Step 4 for the corresponding domain that the bead represents. We used the LorDG 17 algorithm to search for the best conversion factor within the range [0. Each domain could have a different conversion factor, therefore, the median of conversion factors from all the domains e.
It is worth noting that the adjacent domains are chosen because they have a high enrichment of inter-domain contacts between domains, hence, the distance estimated between them is more reliable. Estimation of the distance between the center of two domain models. An illustration of how the distance between centers c x , c y of the mass of two adjacent domain models x , y is estimated, where i and j are fragments in domains x and y respectively.
Given the 3D models of domains, the distances d xi and d yj can be calculated from the coordinates of the centers i. The distance between the centers of two adjacent domains, d xy , calculated above, are then divided by their corresponding distance in the low-resolution model to obtain a scaling ratio.
The final ratio used to scale the low-resolution model is the median of these estimated ratios. The centers of mass of the high-resolution domain models are placed at the locations of the corresponding beads or points of the low-resolution model in order to obtain an initial high-resolution model of the entire chromosome for further refinement. In the refinement step Step 7 , we used the LorDG algorithm to adjust the coordinates of all the points of the initial high-resolution models of all the domains to satisfy high-resolution chromosomal contacts.
Starting from the initial, unrefined model produced in Step 6, both intra-domain and inter-domain contacts are used in the optimization to refine it. LorDG uses all contacts to adjust the model to maximize the satisfaction of the contacts. The objective function of LorDG is non-convex and its optimization converges at local optimums. Therefore, the intra-domain contacts that have higher interaction frequency than inter-domain contacts and have already been well satisfied in the initial model are mostly preserved during the optimization.
The optimization in the refinement step mostly tries to satisfy more inter-domain contacts to assemble domain models together. We conducted five tests to evaluate the quality of these models.
Firstly, we calculated the correlation between the fragment-fragment distances in the models and the expected distances calculated from contact matrices. Fourthly, we investigated if the high resolution chromosomal models were consistent with the FISH data 8.
The comparison shows that our models exhibited the 4 loops on four different chromosomes that were identified from the FISH data. Finally, we compared our method with an existing method for high-resolution modeling. The average and standard deviation of the correlations are 0. Considering the large number of expected distances to be correlated for each chromosome e. When contacts with low interaction frequencies are removed, the correlations are better.
This indicates that low interaction frequencies, unreliable contacts drive the correlations down, and our models put a high priority on satisfying reliable contacts with high interaction frequencies. The correlation increases as the cut-off threshold increases, which suggests an increase in the model consistency with the Hi-C data as contacts with low interaction frequencies are removed.
Contacts below each threshold are removed and not used in the Spearman correlation calculation for each chromosome. To check if domain models were adjusted appropriately to satisfy inter-domain contacts, we built models of every two adjacent domains from their contact sub-matrices extracted from the full contact matrix of a chromosome.
The boxplot in Fig. The high average correlations suggest that the domains in the high-resolution full-chromosome models were generally well adjusted to satisfy inter-domain contacts. The average correlations are high.