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Background vocabulary: monomer and polymer
Living things have genetic information stored in a polymer of DNA.
That info gets copied into polymers of RNA.
That is translated, with the help of mRNA, into polymers of proteins.
And each of these steps needs special enzymes.
Life in today’s cells, and even viruses, is wicked complicated.
Hard to imagine all it all evolved, all at once. But who says it had to do it all at once?
Maybe one simple kind of reaction developed, then later, other kinds of reactions, and then over a loooong period of time, even other types.
Life in the very beginning
Perhaps once upon a time, RNA was all that life had.
Pieces of RNA were both the genes and the catalyst.
e.g. RNA could do base pairing with itself, bend, and graph other molecules.
RNA sequences could be copied by other RNAs.
Only later did DNA and proteins evolve.
This is the idea of the RNA world
A hypothetical stage in the history of life on Earth
Idea – RNA developed before DNA and proteins developed.
Alexander Rich first proposed the concept in 1962
Growing amounts of evidence for this is strong enough that the hypothesis has gained wide acceptance.
How is RNA like DNA?
Both can store and replicate genetic information;
How is RNA like an enzyme?
Both can catalyze (start) chemical reactions.
Are any enzymes today made of RNA?
the ribosome is composed primarily of RNA.
Ribosomes are part of many important enzymes, such as Acetyl-CoA, NADH, etc.
So why does life depend on DNA replication nowadays?
DNA is more stable than RNA
What does RNA, and DNA, look like?
How would RNA monomers assemble into polymers?
How could copies be made?
So let us look at the possible in steps, in order.
At the far left is long ago… then an RNA based world of life developed… and later a DNA and protein based world of life developed.
How reliable are genetic ancestry tests/genealogical DNA testing?
What is the technology?
Why would people want to do this?
Learn about family history
Learn about susceptibility to diseases (Parkinson’s, Cancer)
Predicting Side Effects of Pharmaceuticals
Are we really of only the heritage that we think we are from?
What companies are offering these tests?
23andMe, personal genomics and biotechnology company, Mountain View, CA
Family Tree DNA
Example: Tay Sachs
How reliable is the interpretation of the data?
Articles from scientific journals
Why is the interpretation of the data often wrong?
The accuracy of the interpretations will get better over time. But for now they are not great. Why not?
Kristen V. Brown writes:
Four tests, four very different answers about where my DNA comes from—including some results that contradicted family history I felt confident was fact. What gives?
There are a few different factors at play here. Genetics is inherently a comparative science: Data about your genes is determined by comparing them to the genes of other people.
As Adam Rutherford, a British geneticist and author of the excellent book “A Brief History of Everyone Who Ever Lived,” explained to me, we’ve got a fundamental misunderstanding of what an ancestry DNA test even does.
“They’re not telling you where your DNA comes from in the past,” he told me, “They’re telling you where on Earth your DNA is from today.”
Ancestry, for example, had determined that my Aunt Cat was 30 percent Italian by comparing her genes to other people in its database of more than six million people, and finding presumably that her genes had a lot of things in common with the present-day people of Italy.
Heritage DNA tests are more accurate for some groups of people than others, depending how many people with similar DNA to yours have already taken their test. Ancestry and 23andMe have actually both published papers about how their statistical modeling works.
As Ancestry puts it: “When considering AncestryDNA estimates of genetic ethnicity it is important to remember that our estimates are, in fact, estimates. The estimates are variable and depend on the method applied, the reference panel used, and the other customer samples included during estimation.”
That the data sets are primarily made up of paying customers also skews demographics. If there’s only a small number of Middle Eastern DNA samples that your DNA has been matched against, it’s less likely you’ll get a strong Middle Eastern match.
HS-LS1-1. Construct a model of transcription and translation to explain the roles of DNA and RNA that code for proteins that regulate and carry out essential functions of life.
HS-LS3-1. Develop and use a model to show how DNA in the form of chromosomes is passed from parents to offspring through the processes of meiosis and fertilization in sexual reproduction.
HS-LS3-2. Make and defend a claim based on evidence that genetic variations (alleles) may result from (a) new genetic combinations via the processes of crossing over and random segregation of chromosomes during meiosis, (b) mutations that occur during replication, and/or (c) mutations caused by environmental factors. Recognize that mutations that occur in gametes can be passed to offspring.
HS-LS3-3. Apply concepts of probability to represent possible genotype and phenotype combinations in offspring caused by different types of Mendelian inheritance patterns.
HS-LS3-4(MA). Use scientific information to illustrate that many traits of individuals, and the presence of specific alleles in a population, are due to interactions of genetic factors
and environmental factors.
The following intro comes from – Biology 110H Basic Concepts, Stephen, haeffer; Variation in Dominance, Multiple Alleles, Epistasis, Pleiotropy, and Polygenic Inheritance, Penn State.
Sometimes a gene at one location on a chromosome can affect the expression of a gene at a second location (epistasis). A good example of epistasis is the genetic interactions that produce coat color in horses and other mammals.
In horses, brown coat color (B) is dominant over tan (b).
Gene expression is dependent on a second gene that controls the deposition of pigment in hair.
The dominant gene (C) codes for the presence of pigment in hair, whereas the recessive gene (c) codes for the absence of pigment.
If a horse is homozygous recessive for the second gene (cc), it will have a white coat regardless of the genetically programmed coat color (B gene) because pigment is not deposited in the hair.
The figure above demonstrates this scenario. Several of the white horses have genotypes for brown or tan coat color in the first gene, but are completely white because they are homozygous recessive for the gene controlling pigment deposition.
Great resource here – “The term epistasis describes a certain relationship between genes, where an allele of one gene (e.g., ‘spread’) hides or masks the visible output, or phenotype, of another gene (e.g., pattern). Epistasis is entirely different from dominant and recessive, which are terms that apply to different alleles of the same gene (e.g., ‘bar’ is dominant to ‘barless’ and recessive to ‘check’).”
Epistasis: Gene Interaction and Phenotype Effects
By: Ilona Miko, Nature Education 1(1):197
Modeling DNA with Legos
Students learn best when they develop mental models. For many students this is almost automatic – they see diagrams and can internally translate them into… TBA
But for many other students … TBA
One great solution is to physically create models of molecules… TBA
Strengths and limitations of using Legos TBA
(article to be written)
In this next image we see (TBA)
8.MS-PS1-1. Develop a model to describe that (a) atoms combine in a multitude of ways to produce pure substances which make up all of the living and nonliving things that we encounter.
HS-LS1-1. Construct a model of transcription and translation to explain the roles of DNA and RNA that code for proteins that regulate and carry out essential functions of life.
HS-LS1-6. Construct an explanation based on evidence that organic molecules are primarily composed of six elements, where carbon, hydrogen, and oxygen atoms may combine with nitrogen, sulfur, and phosphorus to form monomers that can further combine to form large carbon-based macromolecules.
LSM-PE.5.2.2 Construct a representation of DNA replication, showing how the helical DNA molecule unzips and how nucleotide bases pair with the DNA template to form a duplicate of the DNA molecule.
The information passed from parents to offspring is coded in DNA molecules, long chains linking just four kinds of smaller molecules, whose precise sequence encodes genetic information. 5B/H3*
Genes are segments of DNA molecules. Inserting, deleting, or substituting segments of DNA molecules can alter genes. An altered gene may be passed on to every cell that develops from it. The resulting features may help, harm, or have little or no effect on the offspring’s success in its environment. 5B/H4*
Sexism in science: did Watson and Crick really steal Rosalind Franklin’s data?
The race to uncover the structure of DNA reveals fascinating insights into how Franklin’s data was key to the double helix model, but the ‘stealing’ myth stems from Watson’s memoir and attitude rather than facts.
Matthew Cobb, The Guardian, 6/23/15
The wave of protest that followed Sir Tim Hunt’s stupid comments about ‘girls’ in laboratories highlighted many examples of sexism in science. One claim was that during the race to uncover the structure of DNA, Jim Watson and Francis Crick either stole Rosalind Franklin’s data, or ‘forgot’ to credit her. Neither suggestion is true.
In April 1953, the scientific journal Nature published three back-to-back articles on the structure of DNA, the material our genes are made of. Together, they constituted one of the most important scientific discoveries in history.
The first, purely theoretical, article was written by Watson and Crick from the University of Cambridge. Immediately following this article were two data-rich papers by researchers from King’s College London: one by Maurice Wilkins and two colleagues, the other by Franklin and a PhD student, Ray Gosling.
The model the Cambridge duo put forward did not simply describe the DNA molecule as a double helix. It was extremely precise, based on complex measurements of the angles formed by different chemical bonds, underpinned by some extremely powerful mathematics and based on interpretations that Crick had recently developed as part of his PhD thesis. The historical whodunnit, and the claims of data theft, turn on the origin of those measurements.
The four protagonists would make good characters in a novel – Watson was young, brash, and obsessed with finding the structure of DNA; Crick was brilliant with a magpie mind, and had struck up a friendship with Wilkins, who was shy and diffident. Franklin, an expert in X-ray crystallography, had been recruited to King’s in late 1950. Wilkins expected she would work with him, but the head of the King’s group, John Randall, led her to believe she would be independent.
From the outset, Franklin and Wilkins simply did not get on. Wilkins was quiet and hated arguments; Franklin was forceful and thrived on intellectual debate. Her friend Norma Sutherland recalled: “Her manner was brusque and at times confrontational – she aroused quite a lot of hostility among the people she talked to, and she seemed quite insensitive to this.”
Watson and Crick’s first foray into trying to crack the structure of DNA took place in 1952. It was a disaster. Their three-stranded, inside-out model was hopelessly wrong and was dismissed at a glance by Franklin. Following complaints from the King’s group that Watson and Crick were treading on their toes, Sir Lawrence Bragg, the head of their lab in Cambridge told them to cease all work on DNA.
However, at the beginning of 1953, a US competitor, Linus Pauling, became interested in the structure of DNA, so Bragg decided to set Watson and Crick on the problem once more.
At the end of January 1953, Watson visited King’s, where Wilkins showed him an X-ray photo that was subsequently used in Franklin’s Nature article. This image, often called ‘Photo 51’, had been made by Raymond Gosling, a PhD student who had originally worked with Wilkins, had then been transferred to Franklin (without Wilkins knowing), and was now once more being supervised by Wilkins, as Franklin prepared to leave the terrible atmosphere at King’s and abandon her work on DNA.
Watson recalled that when he saw the photo – which was far clearer than any other he had seen – ‘my mouth fell open and my pulse began to race.’ According to Watson, photo 51 provided the vital clue to the double helix. But despite the excitement that Watson felt, all the main issues, such as the number of strands and above all the precise chemical organisation of the molecule, remained a mystery. A glance at photo 51 could not shed any light on those details.
What Watson and Crick needed was far more than the idea of a helix – they needed precise observations from X-ray crystallography. Those numbers were unwittingly provided by Franklin herself, included in a brief informal report that was given to Max Perutz of Cambridge University.
In February 1953, Perutz passed the report to Bragg, and thence to Watson and Crick.
Crick now had the material he needed to do his calculations. Those numbers, which included the relative distances of the repetitive elements in the DNA molecule, and the dimensions of what is called the monoclinic unit cell – which indicated that the molecule was in two matching parts, running in opposite directions – were decisive.
The report was not confidential, and there is no question that the Cambridge duo acquired the data dishonestly. However, they did not tell anyone at King’s what they were doing, and they did not ask Franklin for permission to interpret her data (something she was particularly prickly about).
Their behaviour was cavalier, to say the least, but there is no evidence that it was driven by sexist disdain: Perutz, Bragg, Watson and Crick would have undoubtedly behaved the same way had the data been produced by Maurice Wilkins.
Ironically, the data provided by Franklin to the MRC were virtually identical to those she presented at a small seminar in King’s in autumn 1951, when Jim Watson was in the audience. Had Watson bothered to take notes during her talk, instead of idly musing about her dress sense and her looks, he would have provided Crick with the vital numerical evidence 15 months before the breakthrough finally came.
By chance, Franklin’s data chimed completely with what Crick had been working on for months: the type of monoclinic unit cell found in DNA was also present in the horse haemoglobin he had been studying for his PhD. This meant that DNA was in two parts or chains, each matching the other. Crick’s expertise explains why he quickly realised the significance of these facts, whereas it took Franklin months to get to the same point.
While Watson and Crick were working feverishly in Cambridge, fearful that Pauling might scoop them, Franklin was finishing up her work on DNA before leaving the lab. The progress she made on her own, increasingly isolated and without the benefit of anyone to exchange ideas with, was simply remarkable.
Franklin’s laboratory notebooks reveal that she initially found it difficult to interpret the outcome of the complex mathematics – like Crick, she was working with nothing more than a slide rule and a pencil – but by 24 February, she had realised that DNA had a double helix structure and that the way the component nucleotides or bases on each strand were connected meant that the two strands were complementary, enabling the molecule to replicate.
Above all, Franklin noted that ‘an infinite variety of nucleotide sequences would be possible to explain the biological specificity of DNA’, thereby showing that she had glimpsed the most decisive secret of DNA: the sequence of bases contains the genetic code.
To prove her point, she would have to convert this insight into a precise, mathematically and chemically rigorous model. She did not get the chance to do this, because Watson and Crick had already crossed the finishing line – the Cambridge duo had rapidly interpreted the double helix structure in terms of precise spatial relationships and chemical bonds, through the construction of a physical model.
In the middle of March 1953, Wilkins and Franklin were invited to Cambridge to see the model, and they immediately agreed it must be right. It was agreed that the model would be published solely as the work of Watson and Crick, while the supporting data would be published by Wilkins and Franklin – separately, of course. On 25 April there was a party at King’s to celebrate the publication of the three articles in Nature. Franklin did not attend. She was now at Birkbeck and had stopped working on DNA.
Franklin died of ovarian cancer in 1958, four years before the Nobel prize was awarded to Watson, Crick and Wilkins for their work on DNA structure. She never learned the full extent to which Watson and Crick had relied on her data to make their model; if she suspected, she did not express any bitterness or frustration, and in subsequent years she became very friendly with Crick and his wife, Odile.
Our picture of how the structure of DNA was discovered, and the myth about Watson and Crick stealing Franklin’s data, is almost entirely framed by Jim Watson’s powerful and influential memoir, The Double Helix. Watson included frank descriptions of his own appalling attitude towards Franklin, whom he tended to dismiss, even down to calling her ‘Rosy’ in the pages of his book – a nickname she never used (her name was pronounced ‘Ros-lind’). The epilogue to the book, which is often overlooked in criticism of Watson’s attitude to Franklin, contains a generous and fair description by Watson of Franklin’s vital contribution and a recognition of his own failures with respect to her – including using her proper name.
It is clear that, had Franklin lived, the Nobel prize committee ought to have awarded her a Nobel prize, too – her conceptual understanding of the structure of the DNA molecule and its significance was on a par with that of Watson and Crick, while her crystallographic data were as good as, if not better, than those of Wilkins. The simple expedient would have been to award Watson and Crick the prize for Physiology or Medicine, while Franklin and Watkins received the prize for Chemistry.
Whether the committee would have been able to recognise Franklin’s contribution is another matter. As the Tim Hunt affair showed, sexist attitudes are ingrained in science, as in the rest of our culture.
By Matthew Cobb
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Epigenetics is the study of biological mechanisms that switch genes on and off. Epigenetics affects how genes are read by cells, and thus how they produce proteins. Here are a few important points:
Epigenetics Controls Genes. Certain circumstances in life can cause genes to be silenced or expressed over time. In other words, they can be turned off (becoming dormant) or turned on (becoming active).
Epigenetics Is Everywhere. What you eat, where you live, who you interact with, when you sleep, how you exercise, even aging – all of these can eventually cause chemical modifications around the genes that will turn those genes on or off over time.
Additionally, in certain diseases such as cancer or Alzheimer’s, various genes will be switched into the opposite state, away from the normal/healthy state.
Epigenetics Makes Us Unique. Even though we are all human, why do some of us have blonde hair or darker skin? Why do some of us hate the taste of mushrooms or eggplants? Why are some of us more sociable than others? The different combinations of genes that are turned on or off is what makes each one of us unique. Furthermore, there have been indications that some epigenetic changes can be inherited.
Epigenetics Is Reversible. With 20,000+ genes, what will be the result of the different combinations of genes being turned on or off? The possible arrangements are enormous! But if we could map every single cause and effect of the different combinations, and if we could reverse the gene’s state to keep the good while eliminating the bad… then we could theoretically* cure cancer, slow aging, stop obesity, and so much more.
This introduction has been excerpted from WhatIsEpigenetics.com
How does this happen?
We currently know of three systems that attach to genes, and turn them on or off. More systems may be discovered!
non-coding RNA (ncRNA)-associated gene silencing
More content TBA
Detecting genetic disorders with 3d face scans
Johan at the Phineas Gage Fan Club writes:
Following on from last week’s post on smile measuring software, The Scotsman (via Gizmodo) reports on the work by Hammond and colleagues at UCL, who are developing 3d face scans as a quick, inexpensive alternative to genetic testing. This is not as crazy as it sounds at first since it is known that in a number of congenital conditions, the hallmark behavioural, physiological or cognitive deficits are also (conveniently) accompanied by characteristic appearances. The classic example of this is Down syndrome, which you need no software to recognise. More examples appear in the figure above, where you can compare the characteristic appearances of various conditions to the unaffected face in the middle.
Hammond’s software can be used to identify 30 congenital conditions, ranging from Williams syndrome (a sure topic of a future post) to Autism,
Diagnostically relevant facial gestalt information from ordinary photos
Rare genetic disorders affect around 8% of people, many of whom live with symptoms that greatly reduce their quality of life. Genetic diagnoses can provide doctors with information that cannot be obtained by assessing clinical symptoms, and this allows them to select more suitable treatments for patients. However, only a minority of patients currently receive a genetic diagnosis.
Alterations in the face and skull are present in 30–40% of genetic disorders, and these alterations can help doctors to identify certain disorders, such as Down’s syndrome or Fragile X.
Extending this approach, Ferry et al. trained a computer-based model to identify the patterns of facial abnormalities associated with different genetic disorders. The model compares data extracted from a photograph of the patient’s face with data on the facial characteristics of 91 disorders, and then provides a list of the most likely diagnoses for that individual. The model used 36 points to describe the space, including 7 for the jaw, 6 for the mouth, 7 for the nose, 8 for the eyes and 8 for the brow.
This approach of Ferry et al. has three advantages. First, it provides clinicians with information that can aid their diagnosis of a rare genetic disorder. Second, it can narrow down the range of possible disorders for patients who have the same ultra-rare disorder, even if that disorder is currently unknown. Third, it can identify groups of patients who can have their genomes sequenced in order to identify the genetic variants that are associated with specific disorders.
Quentin Ferry et al, eLife 2014;3:e02020
This App Uses Facial Recognition Software to Help Identify Genetic Conditions
A geneticist uploads a photo of a patient’s face, and Face2Gene gathers data and generates a list of possible syndromes
… Face2Gene, the tool Abdul-Rahman used, was created by the Boston startup, FDNA. The company uses facial recognition software to aid clinical diagnoses of thousands of genetic conditions, such as Sotos syndrome (cerebral gigantism), Kabuki syndrome (a complicated disorder that features developmental delay, intellectual disability and more) and Down syndrome.
How phenotypes lead to genotypes (infographic?)
Scientific journal articles
Detecting Genetic Association of Common Human Facial Morphological Variation Using High Density 3D Image Registration
Shouneng Peng et al, PLoS Comput Biol. 2013 Dec; 9(12)