Showing posts with label mutation. Show all posts
Showing posts with label mutation. Show all posts

Monday, July 13, 2015

Mutation Monday: OxoG is how radiation turns your own water against you!

by Rich Feldenberg

Welcome back to your mutation station.  Today we'll examine how ionizing radiation breaks water molecules apart to form oxygen free radicles (or reactive oxygen species), which then go on to wreak havoc with your DNA.

Most of the damage done to us by ionizing radiation, such as X-rays and gamma rays, are not a consequence of direct hits to our DNA,  but are a secondary effect of the radiation splitting water into highly reactive and destructive molecules - the oxygen free radicles.  It is these oxygen free radicles that then go on to damage our cell's vital components, like DNA.  Water is by far the most common molecule in our bodies, and statistically will be the most likely thing hit by an energetic photon of radiation that strikes us.

The oxygen free radicals are molecular species, such as the extremely reactive hydroxyl radical (*OH),  as well as hydrogen peroxide (H2O2) and the superoxide radical (*O2-).   These are often called oxygen free radicals, but not all of them are technically radicals (having an unpaired electron), so reactive oxygen species is really a more appropriate term.  These reactive molecules can then oxidize susceptible places on the DNA that lead to mutation.  Hydroxyl radical, is by far, the most reactive of the bunch, and basically reacts immediately with whatever is in it's way as soon as it is formed.
1=singlet oxygen (higher energy state), 2=molecular oxygen, 3=superoxide radical, 4=hydrogen peroxide, 5=hydroxyl radical.


A common site of damage is the oxidation of the nucleotide base guanine (G) to produce 8-hydroxyguanine, also known as oxoG.  Whereas, normal guanine will base pair with cytosine (C), oxoG can base pair with both cytosine and adenine (A).  If oxoG happens to base pair with A, then after the next round of DNA duplication there will be a point mutation from the original G:C to the newly mutated T:A.  It turns out that this particular switch is very common in many tumor cells, and may be due to the damaging effects of radiation.

Oxo-G forming an inappropriate base pair with adenine


In this way, the effects of radiation are mainly by turning your own water against you.   In addition to radiation, oxygen free radicals are produced just by normal metabolism.  As we extract energy from sugar molecules, we pass electrons down the "respiratory chain - a set of enzymes in our mitochondria, that eventually react with Oxygen to form water.  During this process, free radicals are produced that have the same effect as those produced by water's interaction with radiation.  It has been estimated that in just one year of breathing - something we all have to do if we are alive - is the equivalent of 10,000 chest X-rays worth of radiation.  Just being alive is dangerous!


References:

1. "Oxygen: the molecule that made the world", by Nick Lane.  See chapter 6 (Treachery in the air) for some of the stats listed.   (a really great book, by the way).

2. "Molecular biology of the gene", 7th edition, by James Watson;  ISBN-13: 978-0321762436  
      Also an awesome text.  




Wednesday, July 8, 2015

Another Clever Mesign Brought To You By Mother Nature

Another Clever Mesign Brought To You By Mother Nature
By Rich Feldenberg


In the paragraphs that follow I’m going to introduce a new term, that I am calling mesign, but first let me remind you of how the world around us appears so well designed.  Almost perfectly designed, if we're not looking too closely.  We observe the beautiful, intricate, complexity of nature everyday.  How can anyone go about their day and not be amazed by the well oiled machinery of nature, such as flowers blooming in the yard, full of nectar for busy bees.  Bees pollinating the flowers on their travels, using their compound eyes to see in ultraviolet light, markings on the pedals that are invisible to us, that guide them to where they need to go to find the nectar and pollen.   

Based on how perfectly each kind of animal and plant seems to fit into all their respective niches, it would be natural for us to assume that the world and all its living things were designed.  It would, that is, if we lived in a pre-scientific culture, but we live in a culture where we’ve fought hard to acquire a well earned understanding of the universe.  A world, where in the last 400 years, at least, the methodology of science has progressively shown us how the physical and biological phenomena that seemed so mysterious to our ancestors can be understood by human minds.  We know today that evolution works at the level of genes to shape organisms that survive and reproduce the best in their environment.  Over the billions of years that life has existed on the earth, complex biological structures have evolved such as eyes to see clearly, kidneys to maintain our internal environment in optimal chemical balance, hearts to pump blood to distant tissues, wings to soar into the sky, gills to extract oxygen from the water, and so on.  Before Darwin it was natural for people to think that all these structures, and their intricate parts, were designed to achieve their apparent purpose.  No one would deny that these things have the appearance of design.  That doesn’t mean that they were purposefully designed, however.  Evolutionary biology has revealed how complex structures, that perform complex operations, arise through the process of natural selection.  

Creationist often claim that certain biological structures are irreducibly complex, and therefore could not have evolved from any lesser evolved structure.  The eye for instance, is commonly sited by creationists as an example of a structure so perfectly made for the job it performs that it had to have been created by a divine designer.  Remarkably, it has been shown how the vertebrate eye could have very plausibly evolved in a series of small steps from more primitive kinds of eyes.  

To create a camera-type eye, like that evolved in vertebrates, you start with a simple patch of skin with light sensitive cells.  This simplest kind of eye can tell light from dark - day from night.  The next step is the formation of a slight depression at the skin surface which will then provide some ability to tell from which direction the light is coming due to shadowing in the depression.  This would seem to have obvious advantages over the creature with a simple flat eye spot.  As the depression deepened you would continue to improve the ability to discern direction.  At some point you would begin to form a pin-hole like camera eye where an image could actually be formed.  A thin transparent tissue over the pin hole might help protect the light sensitive cells inside and would act as a kind of lens as light passed through this tissue.  The shape of this lens tissue could be selected that allows for higher quality lens ability and would also allow the pin hole (now a pupil) to open wider and allow in more light and therefore a clearer image.  

stages of evolution for the vertebrate eye

Each step in the series outlined above, can be found in different animals in nature today, and, as Richard Dawkins, the famous evolutionary biologist has pointed out, “What use is half an eye?  Well, it is 1% better than 49% of an eye.  And 1% of an eye is better than no eye at all”.   Those creature with simple sorts of eyes, like flat worms with tiny eye spots, still use their eyes to their advantage, even though we would consider ourselves essentially blind if you suddenly saw in flat worm vision!

It is still useful for scientists to discuss the structure-function relationships of evolved features in a language that may superficially sound like a discussion of purposeful design, when in fact, they mean nothing of the sort.  For example, it is just plain simpler to use common language such as, “The eye is beautifully designed to allow light to enter through the pupil, and using the lens, focus an image precisely on the retina”.  However, for the biologist, the meaning of this sentence is, “The eye is a beautiful structure, that has evolved through natural selection in a way that allows light to enter the pupil where the lens can then focus it precisely on the retina”.  By using the word design, which is easier and more natural to use in common speech, it can give the false impression that the speaker might really mean she thinks the eye was designed by an intelligent designer when this was not her intent at all.
   
We need a new word for the illusion of design in nature.  Well, relax because that word is here - Mesign.  Mesign would be used to distinguish that the intended meaning was for the illusion of design created by a natural process, such as evolution in the case of living things.  To use our previous example, we could simply say, “The eye is beautifully mesigned to allow light to enter through the pupil, and using the lens, focus an image precisely on the retina”.  There is no misinterpreting the intended meaning of this statement.  

Mesign obviously has its root in the word design, but has been modified to look a little like the word Meme, which Richard Dawkins coined to mean an idea that spreads through a population by use of language and culture, and may even be subject to a process of natural selection, which will determine its prevalence and permanence in a particular society.  I don’t know if mesign will be a successful meme or not, but I feel it could be potentially useful.

Mesign also implies that the design process of a particular feature, being accidental through the process of natural selection, is inevitably going to contain design flaws.  Why wouldn’t it, if it was simply an evolved structure with no grand engineer making any attempt to get the design just right, or performing test and experiments on working models of the design before sending it out for prime time in the real world.  Evolution doesn’t even have any kind of a goal that it is working toward.  Only in retrospect does it seem that the purpose of the evolutionary process was to get to this particular structure, organ, or organism.  To go back to our eye example, there was no intent to go from creatures in the precambrian with light sensitive eye spots to vertebrate eyes with lens, corneas, retinas, optic nerves, and so on.  Our little precambrian worm ancestors were simply in a struggle for survival due to limited resources and the rise of predatory species.  Those creatures with eye spots able to tell day from night, and up from down,  would have had some survival advantage.  Those little guys that may have acquired a gene mutation that caused a depression at the eye spot location during their development may have been favored to survive and pass on their “mutant” genes since they would have some sense of direction due to shadowing in the eye spot depression, potentially allowing them to see a shadow of a predator approaching.  The mutation was random, but the spread of the mutation in the population is not since a favorable mutation, like the one discussed above would be selected for by natural selection.


Many of the features of living things, while amazing, seem poorly designed when inspected more thoroughly.  Instead of intelligent design, it seems clear this is stupid mesign The common passage way of the oral pharynx leading to both the esophagus and the trachea makes every meal a choking hazard.  The fetal decent of the testis from the peritoneal cavity into the scrotum leads to a weak spot in the abdominal wall, making herniation and potential death by intestinal obstruction an unnecessary threat.  And, due to our, in evolutionary terms, recent adoption of bipedalism, childbirth is an extremely deadly activity for both mom and child.  Prior to modern obstetrical care, the mortality rate for infant and mother was extremely high.   The human body would be recalled, and the designer sued if this was an engineered machine.  

When it comes to the appearance of design in the physical world, mesign could be a useful term, as well.  Consider the “fine tuning” problem in physics.  We find that the physical constants have values, such that they allow protons and electrons form hydrogen atoms, clouds of hydrogen gas to condense into stars, which then fuse into heavier elements like carbon, planets made of heavy elements form and allow for the development of life, at least here on earth.  The universe has an appearance of design, and while it is not as clear why this is the case, as opposed to the illusion of design in the living world brought about by evolution, it is still a scientific question that is being actively researched. Science continues to inch its way slowly into the unknown, and at this point, there is no reason to assume that deeper physical laws can not be found that might explain this apparent design of the cosmos.  If certain physical properties of our universe, such as cosmic inflation are found to be true, then these same theories also demand the existence of a multiverse as part of their mathematical structure.  The multiverse, while possibly not observable on its own, could be a reasonable explanation for the physical parameters in our universe.  This is basically because universes with every combination of physical parameters also exist, we just find ourselves in one that has the parameters suitable to our kind of existence because that is the only kind of universe we could find ourselves in.  

Map of the early universe showing temperature variations


To explain a physical property in the language of mesign would be to allow the reader to be clear that the author is referring to a naturalistic process, without any notion of a supernatural plan implied.  An example might be, “Stars are well mesigned to turn hydrogen into helium by nuclear fusion in their cores”.  They happen to do that very nicely, thank you, based on their physical properties of size, mass, composition, strength of gravity and the strong and weak nuclear forces, and so on, but there is no reason to suspect that they were engineered for this purpose.  In fact, most stars, such as the abundant but dim Red Dwarfs, are not efficient at synthesizing the heavy elements necessary for life.  Due to their low mass they will never explode in a supernova to produce the remainder of the periodic table.  A better design might be to have a process that guarantees every star to produce the building blocks of life.  That might be a universe where life was really thriving in every possible corner.  If someone’s intention were to suggest that the stars were designed by a designer, then design would be the proper wording in that case, and there would be no mistake about it.  

It seems better to take some of the ambiguity out of the equation when discussing question of evolution and other natural processes.  Confusion as to an author’s intended meaning, or at times, purposeful misuse of a quote to take it out of proper context might be avoided by using the word mesign when it is called for.  


References and a cool video to watch:
1.  Youtube video of Richard Dawkins demonstrating the evolution of the eye.  

2.  “Evolution of the Eye”,  Trevor D. Lamb;  Scientific American collector’s edition,  July  2015.

3. Wikipedia entry on Meme:   https://en.wikipedia.org/wiki/Meme

Monday, July 6, 2015

Mutation Monday: Lactase Persistence

Welcome back to your Mutation Station.
by Rich Feldenberg

Today we will examine the importance of the LP-mutation (Lactase Persistence-mutation), and its impact on human survival and global colonization.  Creationist like to ask the tiresome question, "name a mutation that increases the information content of a gene".  I don't think they really understand the question that they are asking, but today we will give one example of a simple mutation in human DNA that offered an advantage through natural selection to our species.  There are other examples, and we'll address some of them in later blog entries.

Lactose is a carbohydrate found in mammalian milk.  It is composed of two simple sugars bonded together.  Humans and other mammals evolved to be dependent on mother's milk during infancy, but then to be weaned off milk once the animal was mature enough to begin finding food on its own.  In order to digest lactose the enzyme lactase is required.  Lactase is produced in the digestive tracts of the infants and young mammals, but after weaning is generally no longer produced.  This is to conserve resources in the sense that it makes no sense to keep making an enzyme or other protein that is not being used.


This was true of early humans, as well, but a mutation occurred about 7500 years ago that allowed the lactase enzyme to remain expressed much longer throughout human life.  This mutation would then make drinking milk possible by adult humans, whereas prior to this, adult humans would not have tolerated drinking milk.  It is probably no coincidence that this mutation took place around the same time as the domestication of cattle and goats - sources of milk.  

The mutation, itself is due to a simple switch of one DNA base in the gene coding for lactase, for another base - a single nucleotide polymorphism (SNP).   This lead to a change in the regulation of expression of the gene so that it wasn't shut off when it normally would have been.  To our stone age ancestors, this would have been a wasteful and useless mutation, but with the development of an agricultural society it became indispensable as a way to increase ever rare nutritional sources.  It may have been responsible for allowing humans to migrate into and successfully inhabit Europe.


References:
1. "The Milk Revolution", Andrew Curry; Scientific American special collector's edition.  July 2015.

Monday, June 29, 2015

Mutation Monday (Your Mutation Station): Thymine dimers

by Rich Feldenberg

Welcome back to your mutation station.  Today we'll look at a harmful effect on your DNA due to ultraviolet light, which leads to dimerization of the nucleotide bases thymine (T).  If there are two T bases next to each other in the DNA strand and they absorb UV light they can undergo a photochemical reaction that causes them to link-up.   The double bonds in the base break and then form single bonds to their neighbor.

This blocks normal base pairing on to the other DNA strand of the double helix, and results in a mutation.  Fortunately there are cellular repair mechanisms that can find and fix these errors, but some errors escape detection and cause major harm.  Some melanomas are thought to be due to thyimine dimers caused by the effect of UV sunlight.

Thymine dimers are actually a more specific form of what is called pyrimidine dimers.  The bases thymine and cytosine (T and C) are pyrimidines.  Two pyrimidines can dimerize under the same conditions leading to the same sort of DNA mutations.  You could have T-T dimers (thymine dimers), but also T-C, and C-C leading to the same problems.   So, remember to use sunblock and be careful about exposure to the sun!!