BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: genomes

Potato, Patato No More? Scientists have cracked the code to diversifying the classical starch

With gene-editing technologies such as CRISPR, the variety in produce has been growing at greater rates than ever. It seems as if it is only a matter of time until we get a talking pepper. However, potatoes have been lagging behind. A potato may look quite simple to the human eye, but it is actually quite complex in the world of genomes. For this reason, the human genome was discovered more than 20 years before the genomes that make up a delicious fast food French fry.French Fries

So what is it that makes the potato genome puzzle so difficult to crack? Human offspring receive one of each chromosome from the mother and father, while potatoes receive two of each chromosome from each parent. This results in 4 total copies of each chromosome and in turn four copies of a given gene. A species such as this is called tetraploid. The increase in genes per trait makes editing a given trait that much more difficult. Another task of great difficulty is recreating the potato genome. A task much more difficult than doing so for humans. 

 

Haploid, diploid ,triploid and tetraploid

Scientists Korbinian Schneeberger and Hequan Sun found a clever shortcut. They realized that the pollen cells of potatoes, similar to gametes in humans, contain only half the chromosomes of a body cell. Pollen cells are by this logic, diploid cells containing two of each chromosome. Sequencing the DNA of large amounts of pollen cells allowed the scientists to map out the full genome of a potato. The construction of this genome will make identifying and editing diverse variants of potatoes a much easier task. 

This begs the question of why? Why do we need variety in species of potato? Historical events such as the Irish potato famine of  1840 are a prime example of the importance of produce variety. The famine was caused by tuber blight. A potato is a tuber, a storage stem of plats, and blight is a plant disease commonly caused by fungi. Despite being the most important crop and source of food at the time in most of Europe, the incredible lack of variability of a potato meant no species of potato was resistant to the disease. With concerns over climate change, and an increase in potato popularity; “The potato is becoming more and more integral to diets worldwide including even Asian countries like China where rice is the traditional staple food. Building on this work, we can now implement genome-assisted breeding of new potato varieties that will be more productive and also resistant to climate change — this could have a huge impact on delivering food security in the decades to come.” (Max Planck Institute for Plant Breeding Research), make this issue more important than it may appear. 

How the “unknown” of the human gut microbiome gets in the way of metagenomic studies…

Did you know that the greatest concentration of bacteria lives in your gut? At two or three years old we have a balanced microbiome. While we know a lot about the human gut microbiome, there is a lot that is unknown about it. There has been a lot of improvement in finding an “unknown microbiome” for example, shotgun metagenomics enables researchers to take a sample of all genes in all organisms and allows them to find an abundance of microbes in many different environments.

What we know: 25 Phyla, ~2,000 Genera, ~5,000 Species, ~80% Metagenome mappability, and 316 million genes

What is unknown?: Undetected unknowns, hidden taxa and strain-level diversity (~20% sequences not matching microbial genomes), functional unknowns (~40% genes without a match in functional databases)

For example, one study where researchers studied a stool sample from 2 lean African men and a stool sample from 1 obese European. In the stool, they found 174 new species never seen in the human gut before and 31 new genome species (which can help in later studies). Found within these new species was, Microvirga Massiliensis which has the largest bacterial genome acquired from a human, along with Senegalvirus which is the largest virus in the human gut. We definitely know a lot more about the human gut microbiome than we did, even though there is a long way to go.

However, organizing large numbers of draft genomes from uncharacterized taxa is challenging, and while performing well for bacteria, assembly-based metagenomic tools are less effective when targeting new eukaryotic microbes and viruses.

The human gut microbiome intestines in an obese person vs. a lean person

To make improvements in uncovering “hidden strain-level diversity” it is vital to alter sample-specific associations from the metagenomes and to additionally incorporate as many genomes for each species in reference databases. Most species are “open”, meaning they don’t have an upper bound on the size of accessory genomes and it may seem impossible to reclaim all strain-level diversity; however, preserving “the effort of cataloguing strain variants remains crucial for an in-depth understanding of the functional potential of a microbiome.”

The difficulty is that the microbiome contains viruses. The “functional unknown” of the human gut microbiome is the broadest and most challenging to delve and study further into because there is little known about understanding its pathways and genes. There is one creation though, that helped try and find out what was “unknown” about the microbiome, called the Integrated Gene Catalogue. The Integrated Gene Catalogue of the human gut microbiome which consists of 10 million genes. It groups genes into thresholds, thus the genes then fall into sub-units of gene-families. Locating these genes is only a small part of finding out what they actually do. For example, out of 60.4% of the genes that were annotated, 15-20% of the genes have been discovered, but are stilled labelled “function unknown.” These results show how little is known about genes, their functions, and what is current in microbial communities. There is not enough investment in microbiome research. It is difficult because there could be viruses that can be discovered; however, not enough time is being put into finding it.

Lastly, there is a lot of research going into the human gut microbiome. For example, Fecal microbiome transplantation is where stool from a healthy donor gets placed into the other patients intestine, this transplant usually occurs when more bad bacteria take over the good bacteria in the intestine. However, it could cause more disease which is why further investigation in the human gut can solidify that transplantation could overall prevent a bad bacteria take over. The microbiome field is open to all technologies. Understanding the function of the microbiome still remains the largest challenge researchers face, along with the biggest challenge that “targeting specific genes are irreplaceable”, technology should be able to provide solutions (including microbial transcriptome, metabolome, and proteome, and the automation of cultivation-based assays to scale-up the screening of multiple taxa and genes for phenotypes of interest.)

 

CRISP New Technology: CRISPR

If you have ever seen GATTACA, and thought ‘Wow! I want to edit my genes!’… you may be in luck! CRISPR technology is a simple tool for editing ones genomes. (CRISPR is just a nickname for “CRISPR-Cas9”. ) A genome is an organism’s complete set of genes, including non-coding nucleic acid sequences. CRISPR technology has many different applications, including altering DNA sequences, modifying gene function, correcting genetic defects, and preventing the spread of diseases. Although all of these functions sound positive, CRISPR technology seems to raise ethical concerns.

 

DNA Pencil: Edit Photo By: mcmurryjulie

CRISPR stands for “clusters of regularly interspaced short palindromic repeats”, and is a specialized region of DNA with two definitive characteristics: the presence of nucleotide repeats and spacers. Nucleotides are the building blocks of DNA, and eventually proteins. CRISPR technology was adapted from the natural defensive mechanisms of bacteria. In order to repel attacks, these organisms use CRISPR derived RNA and various Cas proteins (including Cas 9), to attack foreign viruses, or other unknown bodies. CRISPRs are specialized stretches of DNA. The protein Cas9 is an enzyme that acts like a pair of “molecular scissors” which acts to cut strands of a person’s DNA. This protein usually binds to two RNA molecules: cRNA and another called tracrRNA. These two forms of RNA guide Cas9 to the target site, where it will make it’s “cut”. Cas9 cuts both strands of the DNA double helix, making what is known as a “double strand break”. This is how genes are editing.

Bouncing back to the defensive bacteria organisms that started this all, they attack foreign invaders by chopping up, and therefore destroying, the DNA. This allows for the manipulation of genes. These bacteria also use the spacers as a bank of memories which allows the bacteria to recognize viruses and other invaders.

However, due to these discoveries of how CRISPR technology works in bacteria, CRISPR technology is now going to be used to edit the genes of people to change genomes and possible diseases and phenotypes. This has caused some ethical concerns to arise in regards to CRISPR technology being used for human genome editing. Most of the changed involving genome editing are limited to somatic, or body cells, (not sperm or egg cells). Changes in body cells can’t be passed from generation to generation, but changes in sex cells can be passed onto future generations. Some of the previously mentioned ethical concerns include whether it would be a good idea to use this technology to enhance normal human traits (including height and intelligence). Due to these ethical concerns these genome edits are actually illegal in many countries!

Iceman had a lot of problems: Murdered and had a tummy bug

Oetzi_the_Iceman_Rekonstruktion_1 (Recreated model of Iceman)

Photo by Thilo Parg

Iceman reveals a frightening and revolutionary phenomena that suggests that previously considered ancient bacterial strains are much more recent than we had thought.  “Otzi the Iceman” is a mummy discovered in 1991 inside a glacier in the Tyrolean Alps of Italy.  Scientists have done more tests on Iceman’s body than on any known mummy in history but they have also found out a lot about him and human life during his time through stomach, bowel, tooth, skin, and just about any part of his remaining tissue.  For starters, scientific research has theorized that he was a farmer living in Europe over 5300 years ago when he was murdered and left for dead in the freezing Alps.  But Iceman never ceases to provide new scientific insight into human migration and behavior thousands of years ago as scientists have recently discovered an ancient strain of Helicobacter Pyori, a common strain of the stomach bug which is known to cause painful ulcers in the stomach, in Iceman’s gut tissue.

Hp (Helicobacter Pyori) is one of the most common bacterial genomes in existence today as it is found in different strains all over the world and “causes ulcers, cancer, and gastritis—the inflammation of the lining of the stomach—in about 10% of people,” says Ann Gibbons.  Scientists have separated the three main origins of the genome to three continents: Africa, Asia, and Europe, each with their own distinct strains of Hp.  The modern hpEurope strain is theorized to have shared “elements of DNA with types of H. pylori from both Africa and Asia” says Gibbons.  This would suggest an ancient collision of the two strains in one human being who than spread it to more and more people who then migrated to Europe.

Until recently, no one could test this theory.  Months ago, imaging conducted on Iceman’s stomach and gut suggested that his gut tissue and stomach contents were quite well preserved so scientists jumped right to testing them through multiple biopsies.  They discovered two things: he had a full stomach (before he died he stuffed down a bunch of ibex meat) and that he inhabited an strain of hp traced to India and South Asia.  This tells us that “The ancestors of early European farmers such as Ötzi must have carried H. pylori with DNA from Asian strains perhaps in the Middle East before they migrated to Europe. Then, new immigrants carrying African microbes arrived in Europe much later, after Ötzi lived. The two types of microbes mixed in these migrants,creating today’s European strain much more recently than expected” according to Gibbons.

All this data goes to show is that the formation of the “modern” form of hpEurope looks like it had been formed by a just a few unlucky individuals “who were coinfected with two strains, producing a particularly adaptive hybrid type that spread rapidly in Europe,” Gibbons indicates.  This shows scientists that bacterial genomes can adapt to human activity and migration much faster than we thought they could and thanks to the wonders of Iceman’s health problems, we can now trace more deeply the behavior of ancient vs. modern bacterial genomes.

Original Article

 

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