Saturday, November 16, 2013

Essential DNA Required for Life

If one believes in evolution, it is important to know what is required for life. Not just what environmental conditions are needed, but also what biochemical conditions.
It is often quoted that there are 250 essential proteins required for basic life. To have life, you need 250 proteins so it was thought. While those were previous guesses it is now possible to determine what parts of DNA are essential for life. A study released in the journal Molecular Systems Biology provides a method of testing just that. Not only  do they give a method they also performed the test on a “simple” bacterium (Caulobacter crescentus). 
The complete genome of this bacterium was sequenced in 2001. Which helps tremendously with the task of determining which parts are essential for its survival. It is important to know that just because the genome was sequenced does not mean that the function of all the pieces is known, just that the nucleobase sequence that makes up the DNA is known.
With the bacteria in hand, these researchers from the Standford University School of Medicine took a close look at exactly what parts of DNA are required for this bacteria to live in the lab.
“This work addresses a fundamental question in biology: What is essential for life?” said Beat Christen, PhD, one of the co-first authors of the new paper and a postdoctoral scholar in developmental biology. “We came up with a method to identify all the parts of the genome required for life.”(1)
What is essential for life from a biochemical standpoint? They came up with some interesting conclusions which dwarf the previous estimates.
In total, the essential Caulobacter genome was 492,941 base pairs long and included 480 protein-coding genes that were clustered in two regions of the chromosome. The researchers also identified 402 essential promoter regions that increase or decrease the activity of those genes, and 130 segments of DNA that do not code for proteins but have other roles in modifying bacterial metabolism or reproduction. Of the individual DNA regions identified as essential, 91 were non-coding regions of unknown function and 49 were genes coding proteins whose function is unknown. (1)
We are told, “that 12 percent of the bacteria’s genetic material is essential for survival under laboratory conditions.” (1) Sounds like a small percentage overall, but keep in mind that this essential genome was 492,941 base pairs long. These are base pairs that are needed for life in this bacterium. This means that 985,882 amino acids were needed in the correct arrangement to allow life for this bacterium. The implications this has for the unaided formation of the first life are staggering. (While we could stop here and calculate the apparent overly absurd odds of this happening, such a calculation would serve little purpose. As a side note, creationist literature often attempts to calculate the absurd odds of things happening the way evolutions claim. Many set up straw men with these types of processes. I think that more often than not those types of calculations oversimplify the problems and ashamedly make a caricature of the opponents position. This type of “argumentation” is best left off the table if any real headway is to be made with this issue. While I do believe that such odds could be calculated at a rudimentary level, it could never be done to complete satisfaction without knowing all the factors involved. We do know, however, that the improbability is greatly increased because of the sheer number of correctly sequenced amino acids needed.) The researches did find 480 protein coding regions that are essential. This nearly doubles the previous estimates of how many proteins are needed for life. While is is a bit of an extrapolation to say that all of those 480 proteins are needed for life I think we can say that if that part of the DNA is needed it stands to reason that so are those proteins. They also found 91 essential coding regions and 49 coding regions that have unknown function.
“There were many surprises in the analysis of the essential regions of Caulobacter’s genome,” said Lucy Shapiro, PhD, the paper’s senior author. “For instance, we found 91 essential DNA segments where we have no idea what they do. These may provide clues to lead us to new and completely unknown bacterial functions.” Shapiro is a professor of developmental biology and the director of the Beckman Center for Molecular and Genetic Medicine at Stanford. (1)
These 91 essential DNA segments that are of unknown function were still found to be essential to life! This reminds me of the old vestigial organs argument often used in support of evolution. That is right, just because we don’t know the function does not means there isn’t one. See the previous discussion on pseudogenes for another example of that type of thinking.
This new research helps to contribute to our (mis)understanding of an evolutionary origin of life, and, I think, push us toward accepting that a transcendent creator is responsible for life.
1. Digitale, E. “New method reveals parts of bacterium genome essential to life”. Stanford School of Medicine news release, August 30, 2011, http://med.stanford.edu/ism/2011/august/shapiro.html

Wednesday, October 2, 2013

So Called Pseudogenes are not Junk

Yesterday I came across this interesting article in the journal RNA on the subject of pseudogenes. The majority of scientific papers I read typically would be of no interest to the average person. This one however sparked my interest because of it’s relationship to a number of exciting areas. Not just in science, but also in theology and religion.
This paper (titled “Pseudogenes: Pseudo-functional or key regulators in health and disease?“) argues for the usefulness of so called “junk DNA”. Typically this junk DNA is used to support evolution. They point to it saying that these genes used to be active in our evolutionary past and have since “suffered a knock-out blow” mutation and are now a non-functioning remnant of evolutionary history. For some reason these genes became non-functioning and are called pseudogenes (from the greek ψευδής usually meaning “false”). These false genes seem to correspond to genes that our supposed evolutionary ancestors possess; that are still active in these other species. Evolutionary genetics expert Jerry Coyne explains pseudogenes in his book Why Evolution is True on page 67 this way:
“Thirty years ago we couldn’t test this prediction [that we expect to find "dead" genes if evolution were true] because we had no way to read the DNA code. Now, however, it’s quite easy to sequence the complete genome of species, and it’s been done for many of them, including humans. This gives us a unique tool to study evolution when we realize that the normal function of a gene is to make a protein – a protein whose sequence of amino acids is determined by the sequence of nucleotide bases that make up the DNA. And once we have the DNA sequence of a given gene, we can usually tell if it is expressed normally – that is, whether it makes a functional protein – or whether it is silenced and makes nothing. We can see, for example, whether mutations have changed the gene so that a usable protein can no longer be made, or whether the “control” regions responsible for turning on a gene have been inactivated. A gene that doesn’t function is called a pseudogene.
And the evolutionary prediction that we’ll find pseudogenes has been fulfilled – amply. Virtually every species harbors dead genes, many of them still active in its relatives. This implies that those genes were also active in a common ancestor, and were killed off in some descendants but not in others. Out of about thirty thousand genes, for example, we humans carry more than two thousand pseudogenes. Our genome – and that of other species – are truly well populated graveyards of dead genes.”
It should be pointed out that just because a functional protein is not made does not therefore indicate that that section of DNA is of no use as Dr. Coyne implies here. This book was written in 2009 before much evidence had been found to support the idea that pseudogenes have important functions and are not “junk DNA”. Chances are that you have heard this argument, similar to Dr. Coyne’s, from others using this junk DNA to support theistic evolution. At face value the objection seems valid.
  1. These genes have no apparent function and are therefore useless junk
  2. God does not make useless junk
  3. Therefore, they must be the result of millions of years of random evolutionary mutations
You see, if these pseudogenes are the result of random mutations, then they would not be useless junk that God made. For surely pseudogenes would be a necessary consequence of the evolutionary process. Indeed I would expect such a thing if evolution were true. If God used these genes to accomplish his purpose through evolution then these pseudogenes become a tool used by God and are therefore not “useless junk that God made”.
This is one line of argumentation that Francis Collins uses in this book The Language of God to support theistic evolution. In fact you can see the talk that Dr. Collins gave in early 2008 during the Veritas Forum at U.C. Berkley entitled “The Language of God: Intellectual Reflections of a Christian Geneticist”.  He discusses his belief that evolution has been proven here and his discussion of pseudogenes beginning here. In this video he states (at 50:48), “If God in fact had created the human genome independently, as an act of special creation, why would God have placed in this very position a non-functioning gene?” He takes this as proof for evolution saying (at 51:4), “It becomes extremely difficult to avoid the conclusion that we are descended from a common ancestor as are other living things. The alternative requires you to place God in the position of being a bit of a charlatan of actually having put information into the genome to purposefully mislead us into drawing a conclusion that is not in fact correct, and that does not sound like the God I worship.” This statement should make your skin crawl just a little bit. Accusing God of being a charlatan because of a conclusion that you draw, which may be an incorrect one, is scary!
Arguing against “junk DNA” used to require the creationist to say that we just don’t know the function yet. We would content that there is some function that these pseudogenes serve we just do not know what it is presently. The fact that animals possess similar genes that are functioning could just be evidence of a common designer and there is a reason for them – we just don’t know it yet. This is postulated by our opponents as not truly answering the argument. If there was doubt before, there is now peer reviewed academic work in respected scientific journals claiming that the pseudogenes studied do in fact have a function.
The abstract of this RNA paper states:
“Pseudogenes have long been labeled as “junk” DNA, failed copies of genes that arise during the evolution of genomes. However, recent results are challenging this moniker; indeed, some pseudogenes appear to harbor the potential to regulate their protein-coding cousins. . . In this review, we describe the ways in which pseudogenes exert their effect on coding genes and explore the role of pseudogenes in the increasingly complex web of noncoding RNA that contributes to normal cellular regulation.”
It seems these “pseudogenes” do in fact have a use. In the conclusion of their work they state:
“The evidence that some pseudogenes can exert regulatory effects on their protein-coding cousins is mounting. Such functions appear to be mediated by noncoding RNAs produced from active pseudogenes.”
This “noncoding RNA” simply refers to RNA that is not used to produce proteins. So we have here pseudogenes that produce noncoding RNA that help regulate cell processes. Just because the pseudogenes do not make function to make proteins (which is why Dr. Coyne says they are junk and why he thinks our genome is a graveyard of dead genes – see the above quote) they do function to make these RNAs which are vital to regulate cells. This means that pseudogenes are not junk! They are actively involved in producing RNA that is important for cellular regulation. This is far from being a grave yard of deadness!
The scientists report in this RNA paper that they took particular pseudogenes and mutated them. They then found that there was a loss of regulatory specificity that arrises in the cell that these newly mutated pseudogenes were placed in. This gives strong evidence that the pseudogenes play an important role in cells. They also found that if the pseudogenes fail to function this can contribute to cancer. These pseudogenes must be useful in cells to somehow help prevent cancer.
Another interesting conclusion they come to is the fact that pseudogenes have largely been “overlooked” so much so that it is difficult to get probes for pseudogenes commercially. It is difficult to study pseudogenes because there are hardly any probes available that allow one to study them!
“For the large part, pseudogenes have been overlooked in the quest to understand the biology of health and disease, to the extent that pseudogene probes are often absent from commercially available microarrays. As evidence emerges that pseudogenes are deregulated in disease, and indeed that their deregulation can contribute to diseases such as diabetes and cancer, the prevalent attitude that they are nonfunctional relics is slowly changing.”
Who would want to study a non-functioning pseudogene anyway? Especially since we know ahead of time that they are just junk evolutionary remnants. Here is a good example of evolutionary presuppositions interfering with good science. Of course there could be other reasons and this may not be the primary one, but I think it surely plays a role.
Next time you hear anyone using pseudogenes to support evolution feel free to challenge this assumption and point them to RNA (2011) vol. 17  pages 792-798.