Many genes have the same function whether they are inherited from the father or the mother. However, few genes are active only when they are inherited from mother & others are active only when they are inherited from father. This fact makes us raise our hands with a few questions: when we recieve genes of same function from both parents, which one’s action will predominate? and what are the basis of this selective predomination of action? Here comes the rule of what is known as “Genetic imprinting” where certain genes inherited from a certain parent will be silenced by an epigenetic mechanism rendering them inactive. This process happens mainly during the development of gametes.

       The fraction of imprinted genes in the human genome is still unknown, however studies refer that 10%-25% of mouse genome is imprinted.

image credit:

        www.bioteach.ubc.ca             

              Imprinted genes are localized in certain clusters in the genome where the whole cluster is silenced by methylation through certain methylases that act mainly by addition of methyl group to cytosine of spesific CpG dinucleotides within the clusters, so reducing the expression of the rest of genes in the clusters. However, Genetic imprinting is liable to modification along generations, for example if a male recieved imprinted genes from his mother, if it happens that this male will have a daughter, these imprinted genes he recieved from his mother will be activated by another process known as acetylation, where acetylated genes are actively tarnscribed. Thus, whether genes are imprinted or not depends only whether they came from a mother or father & is not a trait being passed through generations ( i.e. Non Mendelian pattern of inheritance). Diseases and developmental disorders are associated mainly when ceratin genes fail to be imprinted. Cancers have deen correlated with failure to imprint growth factors.

Two years ago, the project of sequencing the Neanderthal genome started. They (Max Planck Institute & 454 Life sequencing) promised to end by this year. Well, they kept their promise. Frankly, some mitochondrial DNA sequences (mtDNA) have been published but contamination was the major defect in those published sequences. They collected more than 60 bone specimens from museums (We’re talking about 38,000-year-old bone); they repeated the sequencing for 35 times in the same clean room of extraction to avoid contamination with human DNA.

From the total 13 protein-encoding genes of the sequenced mtDNA, they identified only one with amino acids difference than the human sapien version. It is cytochrome c oxidase subunit 2 (COX2 – part of the respiratory chain), but even this difference has no significant effect on the functional domain of COX2. They hope to answer this questions in a few months: Why Neanderthals died out & human didn’t?!

We already know that Neanderthals & humans share 99.5% of the sequence, but answering questions about having a common ancestor & extinction through absorption (bred with humans) needs lots & lots of researches, collecting & sequencing samples at different time intervals to come with hypotheses. The mtDNA is not enough as Trinkaus (an expert on Neanderthal biology and human evolution) said: “The genome sequence data may tell us something about the selection of a couple of proteins, but it tells us nothing about language or social behavior.”

Image credits:
Reconstruction of a Neanderthal child from Gibraltar: http://en.wikipedia.org/
First complete Neanderthal genome sequenced: http://www.nature.com/

Once upon a time, in 2003, a French team discovered a giant virus infects amoeba. It was isolated from a cooling tower in the UK. They were so excited because it was so huge with a genome contains 900 protein-encoding genes (The words giant/ huge are totally hilarious. It’s not “Hulk”, it’s just a virus). It’s visible under the optical microscope. They named it Acanthamoeba polyphaga mimivirus (APMV). The prefix “mimi” is for mimicking microbe. Now, the same team “Raoult’s team” reported the isolation of another strain of those giant viruses but this time it was isolated from a cooling tower in Paris. They named it “mamavirus” because it was slightly larger than the previous giant virus (APMV), but it wasn’t alone. It was associated with its satellite, a small virus has 21 protein-encoding genes infects it, hijacks its viral factory making copies of itself, hindering the ability of the mamavirus to replicate/ make its own copies, so the number of the mamavirus drops in the infected amoebae. They named it Sputnik after the first man-made satellite. It’ll be the first isolated “Virophage”. How did I know about it? From the amazing blog of Dr. Ramy K. Aziz, “Microbes“.

The story won’t stop at this discovery. The discovery of the virophage will strongly suggest that “Viruses are alive” because they share something with other living domains of life, they can be infected, they can get sick, what makes all health-care providers totally thrilled because there’s something stronger than viruses which could be used to fight them, but “It’s too early to say we could use Sputnik as a weapon against big viruses or to modify them,” says co-author Bernard La Scola.

One more thing about Sputnik, 3 of its genes are closely related to APMV which suggests horizontal gene transfer between giant viruses caused by Sputnik. This is so “bacteriophagic”, reminds me with the whole insertion/ lysogenic mechanism between phages & bacteria. The isolated sequences from the ocean are closely related to the genome sequences of giant viruses & their satellite (Sputnik) . They infect plankton. “It suggests there are other representatives of this viral family out there in the environment,” Koonin says.

Image credits:
Giant mamavirus particles (red) and satellite viruses of mamavirus called Sputnik (green). http://www.nature.com/

Many drugs can’t do it, but GBS can!

Bacterial meningitis is one of the leading causes of death and disability among childrens.  Meningits occurs when bacteria cross blood brain barrier  (BBB) after interacting with human Brain microvascular endothelial cells (hBMECs) . Although these cells are exhibiting tight junctions and lacking pinocytosis, some bacteria could cross it and this demonstrates an interplay between host cells and some bacterial factors.

Scientists at USCD school of medicine used a process involving generating and screening of many group B streptococcus (GBS)  in tissue culture model of human BBB (consisting of immortalised hBMECs) . This culture maintained the normal function of human BBB.

 They identified a gene called iagA gene encoding for a glycosyltransferase. A predicted product of the iagA glycosyltransferase is the glycolipid  diglycosyldiacylglycerol involved in anchoring lipoteichoic acid (LTA) and consequently, enhances BBB invasion.

Allelic replacement of the iagA gene,so that the resulting mutants are lacking the gene, shed LTA into the media. As a result, mice infected with mutant gene exhibited less mortality rate -up to 90 percent- compared to wild-type infected mice. Mutant-type infected mice developed bacteremia  as WT which proves the fact that iagA gene plays the central role in BBB invasion without significantly affecting adhesion or blood survival.

Since bacterial meningitis may cause infected children death or many complications as permanent cognitive deficits, blindness, deafness or seizures, an early treatment may help reduce high rates of death and disability.

This early treatment may be much more easily designed after these findings by blocking LTA anchoring on bacterial cell surface.This will help preventing meningitis even though bacteriemia has taken place.

The journal of clinical investigation has the full story.

As seen on Oprah :), a new state-of-the-art blood test “Biophysical250” is available for a price tag ranging from $1500-3400 that actually determines the length of your telomeres, and thus give doctors an idea of how a certain individual is aging.

What are telomeres?

The chromosomes are often compared to shoelaces and telomeres to the plastic wrapping found at both ends. They are repeated sequences of nucleotides whose function is to maintain the integrity of our genetic code while the cell is dividing. This is mainly because during DNA replication, primers don’t attach to the very end of the strand. Instead, they often ‘miss’ a few nucleotides on both ends and if that were the case, then our genetic code would eventually vanish. This is why telomeres are very important.

Normally, as human beings, our telomeres start off with 8,000 base pairs which decrease each time the cell divides by 30-200 bp each time and may go as low as 1,500 bp in elderly people. Eventually when telomeres become too short, the cell stops dividing, becoming inactive ‘aging’.

An interesting hypothesis about telomeres is that stress is thought to play some kind of role in the determination of their length. In other words, the more stressed out you are, the shorter your telomeres become as you age. Needless to say, once stress has been coped with, it is thought that the rate at which telomeres shorten decreases dramatically which might be essential to longer healthier lives.

For more information, click HERE

July 2008: Santa Cruz, University of California

A surprising type of gene regulation found in mammals under the influence of RIBOZYME

A ribozyme, as the name implies, is an RNA molecule that can catalyze a chemical reaction. Although, RNA is mostly known to play a role in the encoding of genetic info, leaving the catalysis of biological reactions up to enzymes made out of protein. Now, scientists are discovering that RNA might be taking part in both.

The hammerhead ribozyme, previously known to be associated with viroids “plant viruses”, has been found in mice, rats, horses, and other mammals, embedded within certain genes & controlling their expression. Example of such genes are those involved in the body’s immune response & metabolism of bone. In these genes, the mRNA contains sequences that form a hammerhead ribozyme.

The hammerhead ribozyme is a self-cleaving molecule that cuts itself in two. That way, the protein translation is prevented & therefore, no gene expression takes place. To turn the process back on, the self-cleaving action is stopped. Exactly what shuts off the ribozyme action is not known, but assumed to be there.

Two interesting points come up now:

1. The hammerhead ribozyme sequences first appeared in the genomes of rat & mice and then turned up in other mammals but was not found in the corresponding human genes which suggests that a different mechanism DOES exist regulating those genes in humans.

2. The genes, being regulated by a hammerhead ribozyme, are involved in the immune response & in bone metabolism. Such finding can be targeted by the pharmaceutical industry to combat certain autoimmune diseases & bone disorders, which offers potential for better & safter healthcare treatment in the future.