The Y chromosome isn’t going anywhere… at least for a while

The Y chromosome isn’t going anywhere… at least for a while


Opposing the popular theory about the gradual mutation of the “Y” chromosome in the human male, scientists from the Whitehead Institute for Biomedical Research in Massachusetts have reportedly confirmed that the chromosome's genes are very unlikely to change for at least several million years. Hundreds of millions of years ago, the “X” and “Y” chromosomes in the human genetic makeup matched up very smoothly; in much the same way as the other 22 autosomal chromosome pairs in humans still do to this day.

Originally, the two human sex chromosomes exchanged genes as was necessary for appropriate gene repair, which effectively avoided many serious mutations in the DNA. Approximately 166 million years ago, however, a sizable portion “Y” chromosome was turned around and incorrectly inserted into one mammalian ancestor of humanity, which changed the very shape of the chromosome, giving it the characteristic “Y”-shape that it now possesses. This serious mutation rendered the human sex chromosomes incapable of trading genes, and this was inherited to the next generation. Previously, scientists had accepted the fact this genetic anomaly would result in the gradual elimination of the Y chromosome, leaving the male gender with an “X0” chromosome pair, which is more simply an “X” chromosome not attached to anything else (Hughes, et al, 2012).

Chromosomes reside within cellular genetic material. In a human somatic cell, there are normally 46 chromosomes existing as homologous pairs. In simple terms, a homologous pair is a couple of chromosomes with the same lengths, centromere positions and staining patterns (Reece, et al, 2012). In a homologous pair, both chromosomes possess identical genes for heritable characteristics. Human females carry a distinct homologous pair of sex chromosomes in their genetic makeup, often simply dubbed “XX” in reference to the overall shape of the chromosomes. Males do not possess homologous sex chromosomes, and instead carry one “X” and one “Y” chromosome. These two different chromosomes are only very slightly homologous, which was the primary source of the initial theory that the “Y” chromosome may, in due time, disappear as a genetic mutation (Hamzelou, 2012).

Homologous chromosomes, including the Y chromosome.
Dr Jennifer Hughes, the head scientist of the team at the research institute, has ultimately proven that this is not the case. It has been stated that although the “Y” chromosome did indeed lose a substantial amount of its original genes at the time of the first known mutation, there has no been no change in the remaining genes since. Hughes infers that these genes serve highly specific, vital functions in the body, which suggests that there is great doubt that any noticeable alterations to this chromosome will take place, at least for many million years. Currently, little has been confirmed regarding why this genetic anomaly first came about, although, naturally, several theories do exist. Upon comparing the human genome to that of the rhesus macaque, a primate species of which human evolutionary ancestry can be traced back approximately 25 million years, Dr Hughes was able to confirm that males of both species retained the exact same percentage of genes in the “Y” chromosome. This genetic breakthrough was able to prove that after 25 million years, there was no further deterioration since the first known anomaly in the “Y” chromosome, thus disproving the idea that, in time, the “Y” chromosome would cease to exist.

Junk DNA

Junk DNA

In 1953 Watson and Crick were the first to discover the 3 dimensional helix shape that we now know is DNA. They determined the role of DNA is to transfer heritable features from one generation to the next.  (Campbell, et al. 2009) However within DNA there is a section they called Junk DNA.  This is an area of non-coding nucleic acids called introns. (Campbell, et al. 2009)
Initially Watson and Crick thought the Junk DNA had no real use and dismissed it as non-coding proteins.  However scientists now believe that the non-coding DNA that makes up 95-98% of the human genome has a much more important role than originally thought.

In recent years more and more research is being performed investigating the real role of the junk DNA and these findings are conflicting with original assumptions.  In 2010 scientist set out to explore the relationship between a non-coding stretch of chromosome (9p21) and heart disease. They said that individuals with a nucleotide mutation along this stretch of DNA are at greater risk of suffering from the disease.  The non-coding stretch of DNA was deleted in a group of mice. The results showed the mice that had the DNA deleted actually died earlier or developed tumours when compared with mice that had the stretch of DNA intact.  They concluded that the genes that may have been deleted on the stretch of DNA may control or ultimately inhibit cell proliferation in heart and other tissues. Meaning that without these genes, cells in arteries divide faster which build up causing restriction of blood flow to the heart which causes heart disease. (Visel et al, 2010)



Another idea of the possible functions Junk DNA performs comes from research done on the genomes of fruit flies. The genome of the fruit fly is approximately 80% junk DNA and it seems that the rate in which the flies DNA mutates is far less than what was expected. This means that because of no mutations the evolution of the fly has effectively come to a halt. Furthermore, they go on to say humans and mice have similar genomes, each consisting of around 30,000 genes.  However the species are hugely different. They think that it’s not the genes that separate the species but in fact the junk DNA. Humans have one of the largest proportions of junk DNA out of all species. This may explain the complexity of our species. (Andolfatto, P.  2005)

From recent research it seems to be emerging the idea that junk DNA plays a more important role in human existence than first thought. Whether or not experiments on animals can be applied to humans is yet to be seen. The nature of this type of work has many ethical issues and may take years until experiments on humans are possible. Could it be that one day junk DNA will be considered no longer trash and instead treasure? Only time will tell.

Human and dolphin genomes

Human and dolphin genomes

Humans and dolphins, what do these two animals have in common? You might think that the only thing they could have in common is that they are both mammals. You’re right, but there is a much more interesting fact. Dolphin and human genomes are almost the same. Dr. David Busbee from the Texas A&M University has been involved in a project that studies the genome of dolphins (Kolber, 2010). His team did a number of experiments using hybrid chromosomes combining human and dolphin chromosomes to identify the homologous traits. The results showed that 36 blocks were matching on both species (Fig.1&2). The experiment consisted in “painting” the chromosomes with a fluorescent chemical that would show the homologous traits (Fig.3). Busbee said that he was very surprised when he got to see the results. Because dolphins seem so different animals compared to humans, they live in oceans, eat fish and their physiology is far from ours. However, scientists believe that at some point humans and dolphins came from the same branch of the evolutionary tree. This is shown by the fact that dolphins are mammals that breathe air just like us, so it is believed that initially they were living on land and moved back to the oceans at a later time.

Fig1: Homologies between human and dolphin chromosomes detected by chromosome painting

Fig.2: Matrix showing the distribution of conserved chromosome segments between dolphin  and human

 


Fig.3: Painting of dolphin chromosomes with biotinylates human chromosome-specific paints. Yellow are matching traits.

But how is this discovery useful to science and to us? Evans (2010) discussed that because dolphins have such similarity, they are affected by the same toxins and diseases that affect us. For example, they are affected by red tide toxins, chemicals that are present in wastes which we dump in the sea and other toxins that are present in ocean life. Furthermore, not only have dolphins been affected by the same toxins but they also have learned how to fight or block the effects of these dangerous chemicals. So in other words, if we were able to find out how they are able to have immunization to what affects us, we could use this information to cure or fight the diseases that are caused in humans! For example, we could synthetize a vaccine for diseases. Another important fact is that dolphins can fight type 2 diabetes by simply “switching off” the gene that is affected by the illness and so block the effects of it (Gill, 2010). That would mean that we could cure thousands of people much faster. Another way in which this discovery could help science is that scientists have been studying the dolphin’s genome for years, but with little progress because of lack of resources. But with knowing that it is so similar to our genome it would speed up research by up to 20 years! That would save up a lot of time and money.

Chromosome mutations in yeast cells caused by stress

Chromosome mutations in yeast cells caused by stress

When we consider the concept of evolution, we think of genetic changes in a population over time – perhaps over hundreds or thousands of years. However, some organisms appear to have the ability to genetically evolve in just a few days by inducing chromosome mutations in response to stressful conditions. This phenomenon was studied by a team from the Stowers Institute for Medical Research in 2011. By examining the effects of several stressors, including heat and extreme chemical concentrations, they found that chromosomal variations and consequent drug resistance is the result of the action of heat-shock protein 90 (Hsp90).

In the experiment, yeast cells were submitted to high and low concentrations of a variety of chemicals for 12 to 14 hours. Then, the number of colonies of yeast cells that had an uneven number of chromosomes was compared with the number of colonies with the normal number of chromosomes. Many different stress factors increased chromosomal instability in yeast cells. Most significantly, the result of exposing yeast cells to the drug radicicol, even at a low concentration, was a chromosome loss rate about 300 times higher than the control in stress-free conditions. Exposure to a temperature of 50.9°C produced a similar result.

Graph displaying effects of stress conditions on frequency of colonies that are missing chromosomes

Images displaying effects of stress conditions; red colonies have chromosomal abnormalities

The reason for this surprising result is that radicicol binds to the Hsp90 molecule and disrupts its performance and heat also inhibits the protein. Hsp90 aids the correct duplication of chromosomes during cell division so that the daughter cells contain the same number of chromosomes as the parent cell.When Hsp90 is inhibited, replicated cells are more likely to demonstrate aneuploidy, meaning that they are missing or have an extra copy of a single chromosome.

The genetically diverse colonies of yeast produced by radicicol treatment were then exposed to several different drugs and their performance compared to control colonies. The results showed that the survival rates of the radicicol-treated colonies were much higher against all three drugs.


Images displaying comparison of control yeast colonies and radicicol-treated yeast colonies after exposure to drugs

So how does genetic diversity give a population such an advantage when it comes to survival? Genes within chromosomes determine which proteins are produced in a cell. The number of copies of a gene present in a cell may influence the expression of the gene and thus the final physical characteristics of the organism.For example, four of the yeast colonies that survived exposure to fluconazole demonstrated aneuploidy by containing an extra copy of chromosome 8, and by consequence, an extra copy of the ERG11 gene.This gene helps make organisms more resistant to fluconazole, which normally causes damage to the cell wall of fungal cells.


While the study helps explain one of the mechanisms that make some strains of yeast cells drug resistant, it could be useful in predicting the response of cancer cells to certain treatment. The researchers highlighted similarities between yeast and cancer cells, which often have unusual numbers of chromosomes. This is significant because, previously, some drugs were thought to be able to fight cancer by inhibiting Hsp90 and damaging protein production in the cancer cells.However, these drugs may actually produce drug-resistant cancer cells instead of treating cancer.

Stem Cell Thearpies

Stem Cell Thearpies

Stem cell treatments are a major development in genetic and medical history. Stem cells hold the ability to treat many debilitating illnesses although their uses in treatments raise many ethical debates.

Firstly, let’s define a stem cell. A stem cell is an unspecialised cell that can form specific cells such as a heart, lung or tissue cell. A stem cell is a template for all cells. There are two types of stem cells: pluripotency stem cells and adult stem cells.

Pluripotency stem cells are found in embryos and are therefore named embryonic stem cells. Pluripotency stem cells have the ability to form vast numbers of more specific cells in an embryo, allowing embryos to grow and develop into babies. Because embryonic stem cells hold the ability to form a wide variety of cells, they hold great potential when used in stem cell treatments. However, not all people are in favour of using stem cells in medical treatments.

The embryonic stem cells are derived from fertilised human eggs but are destroyed in the process of Somatic Cell Nuclear Transfer or SCNT.

The process of SCNT involves removing the nucleus of the embryonic stem cell and injecting a nucleus from a different cell into the stem cell. The embryonic stem cell injected with the nucleus from another cell can then be cultivated to regrow the cells from which the nucleus was extracted from. The stem cells grown with the injected nucleus can then be used to replace damage cells. This makes regrowing entire organs and spinal cord tissue possible. This technique was first published by Harvard University in 2008. Some people may find this distressing as they believe SCNT is destroying potential human life.

However, adult stem cells can also be used in stem cell therapy. An adult stem cell is a tissue specific stem cell and can be found in skin, bone marrow, hair follicles and many other sites around the body. Unlike the embryonic stem cells, they are only able to reproduce a specific cell, as the name suggests. For example, an adult stem cell found in the skin can only reproduce to make other skin cells.

Scientists have discovered a technique to make adult stem cells behave like embryonic stem cells. This is called induced pluripotency or iPS. The iPS stem cells have been genetically modified to mimic a pluripotent embryonic stem cell. This is done by using a virus to convert the adult stem cell to behave like an embryonic stem cell and express the genes needed to form the new cell. In 2010, scientists at Standford University have been able to turn fat cells into iPS cells without the use of a virus, making the process of iPS a lot safer and simpler.
The iPS cell treatment is not as controversial as embryonic stem cell treatment but yield the same results, therefore making it a more suitable option in medical treatments.

By using stem cell therapy, illnesses and injuries that may be life threatening or permanently debilitating could one day be treated. With advancing medical and genetic technology, many conditions that were previously thought to be incurable, may well be treatable with stem cell therapies.

Pros and Cons of Designer Babies

Pros and Cons of Designer Babies


Pros:
1.) Designer babies could prevent genetic diseases in babies.
2.) Baby can look and act the way you want it to- hair color, eye color, brains, and athletic ability.
3.) They could, given the knowledge and resources, create an immortal child.
4.) You could see what problems could come for the baby in the future.

Cons:
1.) Everyone could start to look the same, which would cause loss of diversity and culture.
2.) Some people would overuse and abuse their privileges, trying to create the worlds only "genius" or the "ultimate" athlete, parents could choose the life of the child, taking away free will given by God.
3.) It would only help the rich, people who could afford it, and most of the people with genetic diseases in like Africa couldn't afford the help, when they need it more.

Down Syndrome

Down Syndrome

Down Syndrome is a chromosomal condition characterized by the addition of either half or whole of an extra chromosome. Chromosomes are strands of DNA (deoxyribonucleic acid) and proteins which are present in every cell of the body and make up our individual genetic material. Down Syndrome affects 1 in every 800 babies born. The extra genetic material can impair the mental and physical development in a child although the extent of this impairment varies from patient to patient (Gavin, 2012). With current research continuing, the possibilities of minimizing the risk of Down Syndrome will increase.
Down Syndrome is the most common chromosomal disorder in the world. Our cells divide in two ways, firstly is ordinary cell division which is called mitosis in which our body needs to grow. Secondly is in the ovaries and testicles where meiosis occurs. This cell division consists of one cell splitting into two creating sperm and egg cells (refer to figure 1).

Normally during conception 23 chromosomes from the mother and 23 chromosomes from the father are inherited, totaling to 46 chromosomes, and these chromosome contain genetic information. Recent research suggests that in the majority of Down Syndrome cases there is an ovarian nondisjunction during meiosis and he child will obtain an extra chromosome 21 for a total of 47 chromosomes rather than 46 as mentioned earlier (refer to figure 2). A possible cause for this is maternal age although the exact cause is not yet known (Gavin, 2012).

                                                Figure 2: Down Syndrome Chromosomes

The life expectancy of an individual with Down Syndrome is usually around 50 years of age. This is quite low due to almost every system in their bodies being at risk from the effects of Down Syndrome (Schoenstadt, 2012). The exact effects of Down Syndrome are still not known as chromosome 21 codes for approximately 360 proteins although there are some common health problems, such as decreased brain size, congenital heart disease and lens defects. Individuals with Down Syndrome also suffer from increased purine levels which can lead to mental retardation and immune deficiencies. Purine is an organic compound that contributes to the contents of RNA and DNA. As well as health problems there are some physical attributes that are common in Down Syndrome patients for example slanted eyes, shorter neck and shorter limbs (Cunningham, 2008).
There are treatment and therapies available for Down Syndrome patients including physiotherapy to help strengthen muscles, surgery for heart disease  and regular check ups and screening to prolong the life of the individual (Cifra-Bean, 2012). Research in the field of genetics is very promising although it must only be considered in the future as the genes need to be identified and their function be determined before any radical medical procedures are recommended. Interactions between genes can also be a key factor to help minimizing Down Syndrome (Cifra-Bean, 2012).
It is a very promising time in research in Down Syndrome as the advent of the completion of the human genome project is more understood and practiced than ever before. Future research could help improve life expectancy, symptoms and possibly even help repair the chromosome 21 in this devastating chromosomal disorder.

Changing the Gentic Code

Changing the Gentic Code

All life possesses a genome and the nature of that life is determined by it's genome. The genome consists of DNA which is made up of four nucleotides (Adenine, Cytosine, Guanine, Thymine), a series of three of these nucleotides is called a codon (64 codons in total) with each of these codons corresponding to one of the 20 amino acids or one stop codons. These codons are then translated into their respective amino acids until a stop codon is reached. Now what would happen if an organism had a codon that it did not normally have?

                                                            FIG   :  E coli just chiling

In theory an organism with non-naturally occurring amino acids could be made immune to viruses at the very least. Viruses replicate basically by commandeering a cell's ribosome and the other components used for replication.“Viruses depend on the fact that their proteins are encoded by the same codons as those of their hosts”(Young, Discover magazine 2011) If the organism has unnatural codons the viruses are almost certainly not going to have those codons and as such be unable to take over.

A team led by Farren Issacs at Yale University is attempting to answer that question. To do this they have edited the genome of Escherichia coli replacing the E coli's TAG stop codon with TAA another stop codon. First the team identified all 314 TAG codons in E coli, they then created small segments of DNA that had TAA instead of TAG which they mixed into a nutrient rich solution that was swimming with viral enzymes then submerged around a billion E coli in this solution.

The first of two processes MAGE was then used. MAGE or multiplex automated genome engineering, was first used a few years ago and allows bioengineers to do in days what would have previously taken them years. Essentially a specially prepared segment of DNA is placed in a solution with the cell and then electricity is run through the solution. This causes the cell to open pores in it's membrane allowing the DNA inside. Then when the cell next undergoes mitosis it will use this new DNA in the process. The DNA can then be found in the genome of the daughter cells.

MAGE gave the researchers E coli that had some TAA codons, however to create E coli that only had TAA they would have to use another process call CAGE. CAGE or conjugative assembly genome engineering relies on the bacterial form of sex, Bacterial conjugation, where one bacteria transfers genetic material (in this case the TAA codons) to another. The researches separated the E coli into 32 groups then used CAGE until they had a strain with almost entirely TAA codons.

Once the process is complete, the researchers could assign the now unnecessary TAG codon to an amino acid (natural or otherwise) instead of a stop codon. As mentioned before this could make bacteria immune to viruses, (a great thing if that bacteria is used in the production of medicine), what else this could potentially do we can at the moment only speculate. . It should be noted that the E coli seem to suffer no effects from their lack of TAG codons, raising the question what effects the stop different codons have.

DNA methylation

DNA methylation:

 A new approach to modifying cancerous & other diseased cells.


Epigenetics is a fairly new area of genetics, epi- is a Greek prefix meaning above, on or over and epigenetics refers to the study of gene expression other than that of a specific change in the nucleotide sequencing. DNA methylation is a form of epigenetic signature, it is fairly common throughout DNA and is more closely related to cell identity, which is what it sounds like; how’s cells identify themselves. Or for example; how a skin cell, knows not need to produce insulin, while a pancreatic cell knows that it shouldn’t produce pigment. (Health Canal 2012) I won’t dive too deep into the specifics but basically; a methyl group is attached to specific CG sites in the DNA sequence. This is where Cytosine and Guanine are sitting side by side, within DNA. A research paper was published earlier this month in the scientific journal Cell Metabolism titled “Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle”, the subject of the study being how exercise induces instantaneous methylation changes, subsequently altering gene activity to better burn lipids and carbohydrates within mitochondrial function. The research recruited fourteen young and healthy recruits who were punished on an ergometer for incremental short bursts of exercise – fun. Immediately after the pain, more pain was administered in the form of a muscle biopsy which was taken and the methylation then tested. Another biopsy was taken twenty minutes later to examine the difference in methylation levels, and what do you know, they discovered “that acute exercise induces gene-specific DNA hypomethylation in human skeletal muscle.”
Figure A shows the change in methylation, whereas figure B shows the ratio between the levels of methylation on specific genes.

Barrès and co. believed they made a pretty significant discovery, seeing as epigenetics when it first came about wasn’t seen as an important player in the game of genetics. But what they discovered is that hypomethylation is occurring all the time within our DNA, so it’s not as stable a process as once was believed. Their hopes with this is that this can remove some of the fear around tampering with methylation levels within DNA. In other scientist’s defence, this is a fair call as a methylation imbalance has been linked tumour progression (Baylin et al. 1998).

So how does this mean that we can modify cancerous and other diseased cells? Well Barrès believes that they “have shown, that just by exercising, you, yourself manipulate the DNA of your cells. Our DNA is not as stable and unchangeable as previously thought.” (Health Canal 2012). As I said earlier, cell identity and gene expression has much to do with methylation, so how about telling different cells to heal themselves? Or seeing as the original discovery was in fact to do with methylation caused by exercise, what I we could tell cells that they were exercising when they were performing little or no exercise? I can imagine international pharmaceutical giants salivating at this thought – but it could be put to much better use to by simulating exercise for diabetics who have lost both legs to their diabetes. Or perhaps people with severe depression – exercise and fitness is known to improve the symptoms within these people.
Barrès and co. have hungry eyes at this stage and feel that they have opened the door to a whole avenue of new research, but it is very early days so you shouldn’t be getting too excited about that ‘diet pill’ just yet.