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Archive for November, 2007

DNA replication is carried out by DNA polymerase. During the replication, one DNA strand synthesized as leading strand and the other as lagging strand. The leading strand synthesis is continuous, whereas lagging strand synthesis is discontinuous. DNA replication at the DNA ends i.e. telomeres is an altogether different story. If a primer forms at the end of a linear DNA molecule to initiate replication of the leading strand, a single-stranded gap remains at that end after DNA has been synthesized and the primer has been removed. DNA pol cannot fill his gap as no 3-OH group is available onto which nucleotides can be added. If this gap were left unfilled a linear DNA molecule would shorten at each end by the length of the primer with each replication cycle. After many rounds of replication, the molecule would disappear. This problem is known as the linear DNA replication paradox. Besides, as the lagging strand is replicated in the discontinuous manner, it cannot be replicated in its entirety. When the RNA primer is removed, there is no upstream strand onto which DNA pol can build to fill the resulting gap. Without some special mechanism, the daughter DNA strand resulting from lagging strand synthesis would be shortened from the telomeric ends at each cell division.

The enzyme that prevents this shortening of DNA strands is known as telomerase. The enzyme functions as a reverse transcriptase (RNA-dependent DNA polymerase). It holds a small RNA molecule as its component. It was discovered by Elizabeth H. Blackburn et al. The enzyme contains a catalytic site that polymerizes the nucleotides using RNA as the template. The RNA template is part of the enzyme and is approximately 160 bases long. The enzyme uses this RNA as template for adding telomeric repeats to the chromosome ends. First, the 3’ end of the telomere hybridizes with the RNA component of telomerase. Within the RNA sequence is the 6-nucleotide repeated sequence 5’CCCCAA3’ (Tetrahymena) which is complementary to the telomere repeat sequence. Telomerase binds to the 3’ end of to the repeated region. Telomerase binds to the 3’ end of the ssDNA, adding new copies of the TTGGGG repeat sequence. These repeats further extend the single stranded gap left after primer removal. Primers may be added to the repeated segments of DNA and a DNA pol may now fill in much of the gap with DNA.

The repetitive sequence added by telomerase is determined by the RNA associated with the enzyme, which differs among telomerases from different organisms. This extends the dsDNA till it is at least as long as, or longer, than the parent molecule. The single stranded end left after several rounds of addition can be trimmed. The extension and trimming of telomeric DNA is not precise and therefore the number of telomeric repeats is highly variable. Certain proteins, like Rap1 in S. cerevisiae, TRF1 in human beings, keep track of the number of telomeric repeats. It is actually the number of protein molecules attached to the telomere ends that is counted, and not the number of repeats, to decide if telomeres should be added.

The activity of telomerase gradually declines indicating that the DNA molecules must grow shorter with each cell division. This is of little consequence for most cells as they undergo a limited number of cell divisions and then stop dividing: This is the normal ageing process which occurs in all body cells, end at a certain telomeric length, and cells stop dividing. However, if telomerase starts behaving erratically, the chromosomes will not be shortened and cells will continue to divide leading to continuous growth. When cancer cells were examined for the presence of telomerase, the active enzyme was found in abundance, indicating that the linear DNA molecules were being fully replicated. Thus telomerase is found to be essential for cancer cells to continue dividing. Thus, the attention is now turning to the possible clinical application of this knowledge. Research is now under way to determine if blocking the activity of telomerase may be an effective treatment for cancer. Further, studying normal telomere shortening, which acts as a biological clock, may help understand senescence.

 


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Homeobox genes are a diverse set of genes controlling the embryonic development of animals. These genes are characterized by having a 180-nucleotide DNA sequence, the homeobox, which encodes a 60-amino acid protein domain, the homeodomain, of the homeodomain protein. Most of the homeodomain proteins function as transcription factors and participate in the developmental biology of the animal. The homeobox genes have earlier been classified into superclasses, classes, subclasses or groups.

In a study published in the 26 October, 2007, issue of BMC Biology, Holland et al., proposed a revised classification and nomenclature of human homeobox genes. The classification scheme is based on gene class and gene family. Each gene class contains one or more gene families, and each gene family contains or or more genes.

The study recognized 102 homeobox gene families in the human genome. And eleven homeobox gene classes were identified: ANTP, PRD, LIM, POU, HNF, SINE, TALE, CUT, PROS, ZF and CERS. Out of these 11 classes, the ANTP and PRD classes are the largest. A total of 300 homeobox loci were identified, out of which 235 are probable functional genes and 65 are probable pseudogenes.

The study also sheds light on the evolution of human homeobox genes. Read the full paper here.


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The “last mile” problem could be a real annoyance to many a commuter. To overcome this MIT has come up with this innovative and green solution. Known as the City Car, it is an electric vehicle powered by lithium-ion batteries. Some of the salient features of the vehicle are:

1) Electric-powered

2) A sharing service. It will not be used as a personal vehicle. It could be shared by two passengers.

3) Doesn’t use single engine motor; is equipped with four in-wheel electric motors.

4) The car is small, easily maneuverable, 360 degrees of steering capability and stackable.

It has been proposed that stacks of vehicles would be placed throughout the city, and be networked, which would ultimately be linked to the city transportation system. The story at inhabitat states,

“When a person comes gets off a bus or train, they can just hop into one of these vehicles and go about their business. They can either drop it off at the vehicle stack at their destination, if there happens to be one, or returned to their original stack, where the vehicle will be recharged and wait for the next person to take it.”

Read the full story here.


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RNAi is fast emerging as a wonderful tool for inhibiting gene expression in a sequence specific manner. The applications of this technology are two-fold: to study gene function, and use as a therapeutic agent in treating many diseases. As a therapeutic agent it finds applications in antiviral treatments because RNAi has been shown to successfully inhibit virus replication. In a report published on 8 November, 2007, in the Retrovirology, Naito et al., describe the design of antiviral siRNA targeted against HIV-I. To create effective antiviral siRNAs against HIV is a daunting task as the virus mutates at a very high frequency. The researchers first analyzed the HIV-I group M sequences available in the Los Alamos HIV Sequence Database and then found those regions which are highly conserved. Using these conserved regions as target sites, they designed optimal antiviral siRNAs. 21-mer siRNA sequences were generated for all the possible HIV-I sequences. The conserved sequences identified in HIV-I genome included the TATA sequence, polyadenylation signal (AAUAAA), regions essential for viral replication regulation, the primer activation signal (PAS), primer binding site (PBS), packaging signal (ψ), central polypurine tract (cPPT), central termination sequence (CTS), and 3 polypurine tract (3 PPT). A total of 216 highly conserved (>70%) siRNA targets were identified. 41 siRNAs (23 siRNAs out of 216 mentioned above and 18 more siRNAs targeted against moderately conserved regions) were subjected to target mRNA cleavage assay for functional validation using real-time RT-PCR. HeLa cells were cotransfected with vector expressing reporter mRNA that contains the siRNA target site and the corresponding siRNA. Then the potency of siRNAs was monitored by real-time RT-PCR. siRNAs were evaluated for their antiviral efficacy against HIV subtypes B, B’, C and CRF01_AE.
The study clearly demonstrated that 39 out of the 41 siRNAs gave more than >60% silencing; and 26 of the 41 siRNAs effectively inhibited viral replication of all four strains by >80%. The results of the study are quite remarkable and point towards the efficient use of siRNA for inhibiting viral gene expression and replication. The study also paved the way for using siRNAs against divergent HIV-I strains. However, the extreme genetic diversity and high mutation rate of the virus has hindered the creation of a single siRNA effective against all HIV-I strains found in the world. The use of this technology for as a highly effective treatment might be possible in the future and this study could be applied to other pathogens like SARS, influenza virus, etc.

Read the article here.


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In a paper published in the journal Plant Physiology, scientists have demonstrated the creation of computer model of photosynthesis. A photosynthesis model developed by Farquhar et al., 1980, holds great significance in photosynthesis research (Farquhar GD, von Caemmerer S, Berry JA (1980) A biochemical model of photosynthetic CO2 assimilation in leaves of C3 species. Planta 149: 78–90). The model is important in that it links biochemical properties of photosynthesis with in vivo photosynthetic rates. The model of Farquhar et al., 1980, is steady-state biochemical model of photosynthesis, and photosynthesis in nature is rarely at steady state. It is influenced by several environmental factors like light, temperature, oxygen, carbon dioxide and many more biotic and abiotic stresses. The concentration of carbon dioxide has changed greatly over the past 100 years. Considering these factors, dynamic models of photosynthesis have been created (Laisk A, Walker DA (1986) Control of phosphate turnover as a rate-limiting factor and possible cause of oscillations in photosynthesis: a mathematical model. Proc R Soc Lond B Biol Sci 227: 281–302; Laisk A, Walker DA (1989) A mathematical model of electron transport. Thermodynamics necessity for photosystem II regulation: ‘Light stroma’. Proc R Soc Lond B Biol Sci 237: 417–444). These models contribute to further enhance our understanding of control of many photosynthetic properties.

In this remarkable study, a model of photosynthesis has been created on the basis of how resources are partitioned between enzymes of carbon metabolism. The study asks, “Could photosynthetic rate be increased by altered partitioning of resources among the enzymes of carbon metabolism?” In creating the model, the authors addressed this question by using an “evolutionary” algorithm. The algorithm searched for many alternative partitioning strategies (resources partitioned differentially between carbon metabolism enzyme), and the ones leading to increased photosynthetic rate were chosen to build the model. The model looked for changes in concentration of each metabolite. The enzyme activities, the relative abundance of each of the proteins involved in photosynthesis, and initial metabolite concentrations were extracted from the published literature and the whole data fed into the algorithm. The researchers programmed the model to randomly alter levels of individual enzymes in the photosynthetic process. Thus every step of photosynthesis was simulated. The model after several tweaks was able to predict the outcome of experiments conducted in real leaves. The model studied the process for several generations. And after 1500 generations, photosynthesis was increased substantially. To quote from Physorg story:

Using “evolutionary algorithms,” which mimic evolution by selecting for desirable traits, the model hunted for enzymes that – if increased – would enhance plant productivity. If higher concentrations of an enzyme relative to others improved photosynthetic efficiency, the model used the results of that experiment as a parent for the next generation of tests.

The study has far-reaching implications for increasing productivity. The model would help in determining the most suitable growth conditions that would help maximize productivity, and finally, Could the model be extended to the production of better trasngenic plants?

Read the full article here.


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Drosophila melanogaster, the fly extensively studied by TH Morgan, and a powerful model organism highly suited for the study of animal biology and evolution, is known from Africa, Asia, the Americas and the Pacific Islands. The different fly species range from cosmopolitan (D. melanogaster and D. simulans) to the ones inhabiting a single island only (D. sechellia). Their feeding habits are also diverse ranging from generalists to specialist (D. sechellia) feeding on the fruit of a single plant species.

The genome sequences of two fly species, D. melanogaster and D. pseudoobscura are already known, and 9 more species were sequenced (D. yakuba, D. erecta, D. ananassae, D. willistoni, D. virilis, D. mojavensis, D. grimshawi, D. sechellia and D. persimilis). In the first of large-scale genome comparison studies published in the November 8 issue of Nature, scientists at the Broad Institute of MIT and Harvard, the Computer Science and Artificial Intelligence Laboratory (CSAIL) at MIT, and many collaborating institutions, sequenced the genomes of above mentioned 9 species, and then analyzed and compared the genome sequences of the already-sequenced and the newly-sequenced fly species.

This analysis is highly beneficial in understanding the species evolution in a broader perspective and in unlocking the secrets hidden in the genome sequences and functions associated with them. This would also help better understand our own genome. Manolis Kellis, associate member of the Broad Institute, assistant professor in MIT’s CSAIL, and one of the consortium’s project leaders, said, “Having the sequences of many closely related species allows us to study the evolutionary forces that have shaped the fruit fly’s family tree, and to discover the working parts of the fly genome in a systematic way.”

The study revealed that 77% of the approximately 13,700 protein-coding genes in D. melanogaster are shared with all of the other 11 species. The genes required for interactions with the environment and in reproduction display adaptive evolution, as they provided some survival advantage. The researchers also studied the conserved (unchanged) parts of the fly genome and play crucial and similar roles in the fly biology. The investigations further led to the the discovery of 1,193 new sequences that encode proteins. In addition, new RNA genes, microRNA genes and new DNA sequences involved in gene expression regulation were identified. A total of more than 9,000 ncRNA (non coding RNA) genes were annotated from recognized ncRNA classes: The number of ncRNA genes per family is relatively low.

The genome structure is found to be well conserved across the 12 sequenced species. Total protein-coding sequence ranges from 38.9 Mb in D. melanogaster to 65.4 Mb in D. willistoni. Intronic DNA is also largely conserved, ranging from 19.6 Mb in D. simulans to 24.0 Mb in D. pseudoobscura. The analysis of transposable elements revealed that D. grimshawi has the lowest transposable element/repeat content, and D. ananassae and D. willistoni have the highest levels of transposable element/repeat content. The comparative analysis of the 12 fly genomes also led to the discovery of hitherto undocumented transposable element lineage, the P instability factor (PIF) superfamily of DNA transposons. The synteny relationships across the species were also investigated. 112 syntenic blocks were identified between D. melanogaster and D. sechellia (with an average of 122 genes per block), 1,406 syntenic blocks were identified between D. melanogaster and D. grimshawi (with an average of 8 genes per block). The similarity across the genomes is recapitulated at the level of individual genes.

The study also undertook a comparison of cis-regulatory elements, which provided insights into gene regulatory mechanisms operating in Drosophila species.

The landmark study thus: showed genome conservation across the 12 species, identified new RNA genes, demonstrated that multigene families are found in all the species examined, revealed the variations among protein-coding genes, and identified many protein-coding genes that defy the traditional rules of translation.

Read the full paper here.


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The prototype for a solar-powered aircraft has been unveiled by two Swiss adventurers and they hope it would fly around the globe in 2011. The project has been aptly christened Solar Impulse. The solar cells have been integrated into the wings, which will collect sunlight and it will be converted into energy. This energy will be used to power the electric motors of the plane. This plane would definitely be a green marvel, and the technology would be one great step towards reducing our reliance on aviation fuel .

via: Inhabitat


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