An Untangled Problem for Evolution: DNA Topoisomerase.

Background

DNA replicates itself. That is Biology 101. The process is quite complex and any biology student required to rattle off the procedure on an exam can confirm. Although there are separate kinds of topoisomerase,1 they perform the same essential function within the process of replication.

What is topoisomerase?

In each human cell, there are approximately 2 meters of DNA compacted within a nucleus of the diameter of about 10 micrometers.2 For perspective, imagine that the nucleus is represented by a standard basketball. The length of all the DNA compacted into the ball would go round-trip between the earth and the moon just shy of twice. Topoisomerase has the job of ensuring that the shape of DNA is manageable. Add in the fact that DNA is not just a helix, but a double-helix. As one might imagine, the task of trying to do anything productive with this material presents very serious concerns that need to be dealt with. During replication, the topology (i.e. the shape and structure) of DNA and the movement in unzipping result in issues like tangling and kinking, so the process faces a formidable and complex challenge of bioengineering.3 It’s topoisomerase’s job to alleviate those issues so they don’t halt the replication process.4 If DNA cannot replicate, then an organism cannot grow. Additionally, DNA doesn’t just unzip for replication. It unzips in a process called transcription, which, with the help of RNA, is the first half of producing vital proteins in the cell.

Two examples might help illustrate some of the mechanical concerns that arise. Without even trying, the ordinary use of a wired phone produces coiling in the helical cord. No extraordinary spinning or energy is required to produce the effect, but it doesn’t take long for the cable to go from fresh and neat to knotted spaghetti, which seem to never come out. Even if the tangle is gone, there always seems to be a small bend or a missing turn were the tangle was. The second illustration may serve to demonstrate the problem of kinking just prior to cutting the DNA strand in two. To demonstrate the concept, you can take a piece of twine and try to unwind it by pulling away both its twisted strands away from each other. A "Y"-shape forms: the two strands being pulled apart are each the top segments of the "Y" and the rest of the twine is the bottom. Now at some point, enough tension will build up at the center of the "Y" to where you can no longer pull the strands apart. Fortunately, topoisomerase is there to work out these sorts of problems. Its process is so vital and complex that some have referred to topoisomerase as the "magicians of the DNA world"5 because of their uncanny ability to manipulate the DNA strand and master its topology. 

The Problems for evolution

1: Does not fit early evolutionary models for an ancestral topoisomerase

It is still unclear how exactly topoisomerase originated on an evolutionary model, particularly because all the different types of topoisomerase appear to have originated independently of one another.6 A core tenet of evolutionary biology is that all life can be traced to a common ancestor (more technically, LUCA: last universal common ancestor). It is natural to assume that LUCA would have some master topoisomerase that would have developed into the varying domains7 of natural life: Achaea, Bacteria, and Eukaryota. But, this seems to be an incorrect inference that does not align with the actual data.8  It is speculated that topoisomerase might have emerged with either an ancient viral lineage or a LUCA that began with RNA genetic information or a combination of the two.9

These RNA-infused models would be controversial, because such scenarios involve the already contested10 (among researchers in that field) RNA-world hypothesis for the origin of life. And, the progressive introduction of topoisomerase and other necessary replication proteins into the evolutionary lineup seems an inventive proposition, but requires massive amounts of biological informational leaps that are unfounded, especially within the limited time window for the emergence of life on earth that evolution demands. 

2: Conceptual Paradox11

Most of all, the origin of topoisomerase presents a chick-and-egg paradox. To replicate itself the DNA molecule needs topoisomerase to unwind it. And, DNA would need to code for a protein to do the unwinding (in order to pass on the genes to code for topoisomerase). It’s like having a car with no gas. You need to drive to the gas station to get gas, but you need gas to get to the gas station. DNA might have obtained topoisomerase from somewhere else, but the instant it makes a copy of itself, the other strand needs topoisomerase also. The scenario requires the leap to the reality, where DNA actually codes for this protein itself. That is not to mention that the actual mechanics of unwinding get even more complicated, because topoisomerase is able to cut and re-join small sections of DNA, which require precise biochemistry to ensure the right pieces get linked back up with each other and at the proper speed. Too slow, and the DNA doesn’t unwind fast enough for cell division (mitosis) and the cell dies before replication can occur.12 Too quickly, and the cell can set off its own self-destruct sequence (apoptosis) or cause irreversible damage to the genes that results in cancer.13

Conclusion

Lastly, it is also important to keep in mind that this is only a piece of a wider issue for evolutionary biology to explain DNA replication in general: proteins that function as stabilizing clamps, ones that actually unzip the DNA strand, others that error-check the new copies, or the fact that one side of the DNA is duplicated backwards and in sections…

References

1. For the sake of simplicity, all types of topoisomerases will just be noted as 'topoisomerase'.

2. Joseph E. Deweese and Neil Osheroff, "The DNA cleavage reaction of topoisomerase II: wolf in sheep’s clothing," Nucleic Acids Research 37, No. 3 (2009): 738-748.
3. Ibid.
4. James J. Champoux, "DNA topoisomerases: structure, function, and mechanism," Annu Rev Biochem 70 (2001): 369–413.
5. James C. Wang, "Cellular roles of DNA topoisomerases: a molecular perspective," Nature Reviews Molecular Cell Biology 3 (June 2002): 430-440. Wang also makes use of this phrasing in his conclusion of his ‘Minireview’ in "Topoisomerases: Why So Many?" in The Journal of Biological Chemistry vol. 286, 11 (April 1991): 6659-6662.
6. Patrick Forterre and Daniele Gadelle, "Phylogenomics of DNA topoisomerases: their originand putative roles in the emergence of modern organisms," Nucleic Acids Research (2009), 1. The two coauthored a similar article with Simoneta Gribaldo and Marie-Claude Serre, called "Origin and evolution of DNA topoisomerases," in Biochimie (April 2007): 426-446. 
7. A domain is the largest formal classification of living organisms on earth. By contrast, a species is the smallest formal classification.
8. Forterre and Gadelle, 1, 12 (and throughout the article in fact).
9. Ibid.
10. Patrick Forterre, one of the authors mentioned in this article, notes the RNA-world hypothesis, but references its implausibility on page 146 in the chapter entitled Origin and Evolution of DNA and DNA Replication Machineries of "The Genetic Code and the Origin of Life," published by Kluwer Academic and Plenum Publishers. Jonathan Filée and Hanny Myllykallio.
11. This paradox seems lost on some. The article by Allyn J. Schoeffler and James M. Berger entitled, "DNA topoisomerases: harnessing and constraining energy to govern chromosome topology," Quarterly Reviews of Biophysics 41, 1 (2008): 41–101, puts forth: "Understanding topoisomerase specialization is necessary to illuminate the evolutionary interplay between supercoiling homeostasis and the requirement for multiple topoisomerase activities to shepherd DNA through transcriptional, replication, and recombinational processes." The authors acknowledge that topoisomerase is subject to the mechanisms of evolution. How exactly does a mechanism necessary for evolution to work – even at the basic level – get thrown into the mix if it’s not functional with the first strand of DNA? That is not to say that it cannot improve or adapt with time, but it must work from the onset to begin with. And not just it, but DNA and its other requisite enzymes and processes.
12. Deweese and Osheroff, 741-742.
13. On the other hand, however, the essential nature of topoisomerase to cell replication (which requires DNA replication) has been exploited in anti-cancer drugs, which target the topoisomerases within the unwanted cells.

Image entitled "Replication complex" by Boumphreyfr - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons.

The Need For God in Government

A lot of attention has been given to the expression of religious belief in government institutions. We see people more and more claim that religion should not be part of the political process. Religion, they would argue, is personal while politics can affect us all. But politics uses legislation as its tool, and any legislation has a moral makeup. Politicians seek to pass laws "for the good of the people." But how can we understand what "the good" is? Are we justified in holding to any laws at all if we exclude God as the basis of their authority?

Now, this may seem like a strange question. "Of course we should have laws," you may think. "Without laws, how would society function?" That's fair. However, my query is based not on the pragmatic effects of laws, but on their authoritative nature. What right do legislatures have in making rules for me to live by? Why should I be obligated to follow rules created many times by people with whom I disagree? If you're a human being and I'm a human being, then what makes your rules better than mine?

1. Natural Law

Much of what we base western society on today is derived from the concept of natural law. Natural law says that the ideas of good and evil, justice and injustice are divine in origin. When God designed man, He created us in a way so that we can identify these concepts. St. Thomas Aquinas called the ability to discern good and evil "nothing else than an imprint on us of the divine light." 1

The English philosopher John Locke took the concept of natural law even further. Locke said that not only did God design us to recognize concepts of good and evil, but He also created us to be "free, equal, and independent." 2 However, Locke understood that man is also naturally a communal creature. Complete independence was impossible, partly because of the need for other people and partly because of man's sinful nature. Man was selfish and would seek his own benefit above that of his neighbor's. He writes "The state of nature has a law of nature to govern it... that, being all equal and independent, no one ought to harm another in his life, health, liberty, or possessions."3 Locke goes on to explain that because we are God's creation and we serve His purposes every individual must try to "as much as he can, preserve the rest of mankind, and may not, unless it be to do justice on an offender, take away, or impair the life, or what tends to the preservation of the life, the liberty, health, limb, or goods of another."4

2. The Need for Government

It is the need to do justice that creates the need for government. Philosopher John Locke wrote extensively on this concept. Locke felt that because man seeks selfish interests, a governing institution must exist to judge between individuals and to protect the liberties of all its citizenry. "The law of nature would, as all other laws that concern men in this world be in vain, if there were no body that in the state of nature had a power to execute that law, and thereby preserve the innocent and restrain offenders." 5

In forming  governmental structures, Locke said that individuals would willingly give up certain freedoms in order to gain the safety and advantage of living in a community. He termed this exchange a "social contract". We give up a small amount of freedom (such as driving as fast as I like) and instead obey the laws of our community, but in return we become safer on the road since we know other drivers are to also obey those laws. In the end, everyone benefits.

By continuing to live in the community, we continue to agree to that exchange- it is what Locke calls "tacit consent". We participate in and enjoy the benefits of the community's laws, so we therefore support the contract. But all this is predicated on the idea that the state should seek to preserve the rights of the individual as much as possible. When a political system fails to do so, the individuals have the right to dismiss that system as corrupt. 6

3. God and State

Notice that in Locke's view, the government becomes necessary to enforce laws out of a obligation to justice, a justice that is based on the concepts of right and wrong established by an omnipotent God who created all men as equal. If God is removed from the equation, then where does the authority and mandate for the existence of government come from?

Some have suggested that government is there to enforce the will of the majority, but this cannot be the entire basis of government. If it were, then where do the rights of the minority come from? Do we really believe that slavery was right because it was legal or that the majority held it to be correct? Was the extermination of Jews appropriate in WWII Germany because it was legal? Thinking the majority makes something right is a fallacy. Martin Luther King, Jr. said as much when he was questioned by church leaders as to whether his civil disobedience was the Christian thing to do. He wrote:

One may ask: "How can you advocate breaking some laws and obeying others?" The answer lies in the fact that there are two types of laws: just and unjust. I would be the first to advocate obeying just laws. One has not only a legal but a moral responsibility to obey just laws. Conversely, one has a moral responsibility to disobey unjust laws. I would agree with St. Augustine that "an unjust law is no law at all".

Now, what is the difference between the two? How does one determine whether a law is just or unjust? A just law is a man-made code that squares with the moral law or the law of God. An unjust law is a code that is out of harmony with the moral law. To put it in the terms of St. Thomas Aquinas: An unjust law is a human law that is not rooted in eternal law and natural law. 7

We hear so much about the separation of church and state today that I'm afraid we have forgotten the need for God as the basis to justify government's existence and our personal liberties. To be sure, this doesn't mean that we should mandate a specific religion for the citizenry, for that would be intruding on individual liberties. But it does mean that we cannot separate God from government or from liberty and equality. To do so would be to lose all justification for both.

References:

1.  Aquinas, Thomas, Summa Theologica as quoted in Questions That Matter Ed. L. Miller
McGraw Hill Companies, New York 1996 p.503
2.  Locke, John Second Treatise of Government, VIII, 95
http://www.constitution.org/jl/2ndtr08.txt
3.  Ibid. II, 6, 8
http://www.constitution.org/jl/2ndtr02.txt
4.  Ibid. II, 6
5.  Ibid. II, 7
6. The Founding Fathers of the United States appealed to this principle when they sought to gain independence from George III. Locke's influence on the Declaration of Independence is evident in its opening lines: "When in the course of human events, it becomes necessary for one people to dissolve the political bands which have connected them with another, and to assume among the Powers of the earth, the separate and equal station to which the Laws of Nature and Nature's God entitle them, a decent respect to the opinions of mankind requires that they should declare the causes which impel them to separation. We hold these truths to be self-evident, that all men are created equal, that they are endowed by their creator with certain unalienable Rights, that among these are Life, Liberty, and the pursuit of Happiness." As you can see, it is by appealing to God from which the ideas of freedom and equality stem.
7. King Jr., Martin Luther "Letter From the Birmingham Jail"
http://almaz.com/nobel/peace/MLK-jail.html

Would the World Be Better Without Religion? (podcast)

Skeptics such as Richard Dawkins often claim that the biggest evils in the world are perpetrated because of religious beliefs. Does religion cause more wars, more hatred and prejudice than other views? What would a world free of religion look like? Listen into our latest podcast series where I demonstrate why why such claims have no grounding in reality.

• Would the World be Better without Religion? (Part 1)
• Would the World be Better without Religion? (Part 2)
• Would the World be Better without Religion? (Part 3)
• Would the World be Better without Religion? (Part 4)

Why Holy Saturday Is So Important

Dr. N.T. Wright on the importance of Holy Saturday in the Resurrection Week:

After Good Friday comes Holy Saturday, the day of waiting, waiting without hope, without knowing what will come next. Go down deep into Holy Saturday, because once again you are called away from the public arena – extroverts in particular find this hard – and into the stillness where you don’t understand, you don’t have an agenda to work on, you don’t know what it is you want or expect God to do. Without the still, dark privacy of Holy Saturday, the new kind of public message which is the resurrection of Jesus could turn simply into a shallow or angry response to the taunts and violence of Good Friday, answering the world in its own terms. The church is sometimes tempted to do that, to huff and puff and charge off to 'defend' God and the gospel. Holy Saturday commands us to lay down our swords and wait: wait without thought, says Eliot, for you are not yet ready for thought.

Wright, N.T. "God in Private and Public" NTWrightPage.com
http://ntwrightpage.com/sermons/MaundyThurs08.htm 20 March 2008 Accessed: 4/19/2014

Does God Care More about Saving Souls than Strengthening Minds?

Today is Good Friday, the day we remember Jesus' ultimate sacrifice for our souls. It is this day when Jesus was tortured by the thrashing of the Roman whip and the blows of the soldiers. It was this day when he was forced to carry the method of his execution in public humiliation. It was this day that he was put to death in one of the most excruciating ways possible. And he did it so that people could be forgiven of their sins and reconciled to a loving and just God. This is good news: Jesus' death and resurrection means that we can be saved.

Photo provided by AKM Adam

For evangelicals, the salvation message is at the center of their faith. We take the command of the Great Commission seriously. We talk about sharing our faith and leading people to Christ. Churches have outreach services with altar calls. All of this defines Evangelicalism.

I think sharing the Gospel is crucially important. I really do. But sometimes I think we as evangelicals can be a little too myopic in our understanding of the Great Commission and somehow reduce it to telling lost people about Jesus. We get it in our heads that the greatest thing one can do is to lead a lost soul to Christ and all other ministries are subservient to that goal.

This topic came up when a friend and I were discussing how engaging in faith-based conversations online leads to different responses. Sometimes, you will find that people who are not Christians will ask questions about your beliefs. This obviously leads to opportunities to evangelize. Other times, you find out that the other person already trusts in Jesus, but that person's faith may not be very mature. Which type of conversation should we spend more time on? Is God more concerned with saving a soul than strengthening a Christian who is only grasping the basics of the faith?

I don't think so. I think that God is as glorified by the teacher who is growing the hearts and minds of believers as He is by the evangelist who reaches out to the lost. In fact, the epistles of the New Testament are not instructions on how to evangelize, but they are letters written by the Apostles to those who already follow Jesus, correcting their misunderstandings and growing their faith. In fact, the writer to the Hebrews even rebuked the Jewish believers for not understanding as much as they should. In Hebrews 5:11-14 he writes:

About this we have much to say, and it is hard to explain, since you have become dull of hearing. For though by this time you ought to be teachers, you need someone to teach you again the basic principles of the oracles of God. You need milk, not solid food, for everyone who lives on milk is unskilled in the word of righteousness, since he is a child. But solid food is for the mature, for those who have their powers of discernment trained by constant practice to distinguish good from evil.

The analogy of parent and child is a good one here. Newly married couples celebrate with their families and friends when they discover they're expecting a child. It is truly a joyous occasion. However, the important part of being a parent doesn't stop at the birth. The goal of a parent is to train up the child to be a fully-functioning adult, who can be self-sufficient and make thoughtful, mature decisions. Sometimes, this means "wasting" time by allowing the child to learn a task when you could accomplish it yourself so much more quickly. Good parents will invest the extra time into their children so they can learn to be skilled and independent adults.

The same is true in the Christian life. Is it better to simply go out and evangelize everyone, counting the number of converts from service to service or is it better to invest in the lives of believers, training them and weaning them off the milk, so o they can also be effective teachers and evangelists? Certainly this takes more time and isn't as sexy as an altar call, but it is crucial if we want to be faithful to the heart of the Great Commission.

Jesus doesn't just want people to be Christians. He wants disciples. That's what Jesus said when He commanded his followers to go out and share the good news: "make disciples of all nations." We have a glorious message in the gospel. We have a clear command in the Great Commission. Let's make sure we are fulfilling all of it.