Dangling or Not? A Response to Chadwick and Brand

A recent Adventist Review article by Arthur Chadwick and Leonard Brand titled “New Evidence Leaves Macroevolution Dangling” suggests that recent genome science presents a number of challenges to evolutionary interpretations. They present three discoveries—the human genome, epigenetics, and orphan genes, which they propose “have undermined the foundation on which the evolutionary origin of life forms seemed to be resting.”

Discoveries in genome science have certainly revealed the incredible complexity of life as created by God. A three billion base pair human instruction code is not a simple story! At the same time, however, I fear that Chadwick and Brand are oversimplifying things to say that evolution is being dramatically undermined by these results and is “on life support.”  I can almost hear cheers going up from churches across the country upon hearing this news. A close analysis of the scientific literature, however, reveals that scientists have many cogent explanations for the observations made. That is, while they are at times challenged by their discoveries, it might be misrepresenting the situation to suggest that they are befuddled. Very few scientists would say that evolution is “a theory in crisis” as proposed by Michael Denton thirty years ago.¹

I should make it clear at the start that I am a committed Adventist Christian. I believe that the Bible reveals to us the character of God and his message to us in these last days. The world desperately needs to hear the message of hope for the future and love for fellow man as demonstrated to us through the life of Jesus. However, I would disagree that these messages require a belief that the Bible is a scientific textbook. In fact, these messages of hope and love might be significantly undermined by a strident belief in the Bible as a book of science.

While the Bible is not a book of science (although it certainly does speak of the wonder and majesty of creation), science is also not a book about God (although it does suggest an amazing creator). Chadwick and Brand begin their article by stating “The theory of macroevolution asserts that the first living cells, and all types of life, are the result of nondirected, naturalistic processes without the intervention of an outside agency (God).” It is true that this is the typical understanding of evolution—that it is undirected and does not involve God. This is pushed by the most vocal evolutionists out there. However, the theory of macroevolution in fact has nothing to say about God, either for or against. For how could we know scientifically that God was not involved in the process of evolution? What would be the evidence? Science studies the natural world, not the supernatural world. A study of the natural world is not likely to directly show the workings of the supernatural.

But I digress. Let us consider recent discoveries in genome science.

The Human Genome Project

The human genome project was truly an exciting and momentous undertaking. To have the ability to read all three billion letters of our blueprint meant that we could take control of our destiny. If we knew the code, then we might eventually be able to modify the code to fix mistakes that lead to unspeakable suffering and disease. Notably, we should really be talking about this, rather than arguing if evolution is true, because gene editing is currently becoming true,2, 3 and this is not historical science. In just a few years, you can expect to be able to treat many diseases by fixing the germline. This ability to fix the genome suggests that we truly are approaching the time when we will understand the genome.

But when the human genome project was completed, we didn’t understand the code well (and we still don’t, for that matter). The scientific community was surprised to learn that only 2% of the genome encoded all of our proteins. It seemed that our complexity warranted many more protein-coding genes than that found in a small roundworm (C. elegans). Part of the answer to the small number of protein-coding genes had been known since 1977, when the ability of organisms to splice together parts of these genes (exons) in many different ways was first discovered.4 Alternative splicing is a simple way of making many proteins from one gene. It is also thought to be an excellent substrate upon which natural selection can work, leading to increasingly complex organisms: a mutation arises which allows an exon to be easily skipped, the resulting protein has a slightly different structure and hence function which results in a reproductive advantage, thus future generations exhibit a greater proportion of individuals with this new splicing ability. While Chadwick and Brand suggest this is a challenge to evolution, alternative splicing has been shown for some time to fit well into an evolutionary paradigm and to result in many phenotypic differences among species.5

Following the sequencing of the human genome, scientists were particularly interested to know what the other 98% of our genome did. Bacterial genomes were packed full of protein-coding genes, and little else, suggesting that it was the protein-coding genes that were most important and necessary for life. Initial thoughts were that the other 98% of our genome was junk, although this negative terminology was debated for some time within the scientific community because it was understood that it was unlikely to be junk.⁶ As the authors tell us, many diverse functions have been ascribed recently to the other 98% of the human genome through the work of the ENCODE project, further confirming that it is not junk.7 This functionality of the genome, however, does not appear to pose a strong challenge to evolution; in contrast, evolution requires function to work. Without function there can be no selection. In an artificial selection (aka breeding) program, one cannot select for a trait if no region of the genome contains the function to produce that trait. In natural selection, function of genetic sequence determines whether or not that sequence sticks around, whether it is protein coding or not, regulatory or not, 2% or 98%.

Epigenetics

Again, it is true that epigenetics has grown to a vast and exciting field of biology. The idea that our environment can control our genes has to a small degree vindicated Lamarck. Discoveries showing that DNA bases can be modified with chemical groups, resulting in changes in gene expression that can be passed on from generation to generation, have indeed surprised us. We truly are what we eat, and what we eat, even as fathers, can affect the health of our children.8 Of course, if our obesity causes obesity in our children, then they will also have the same diseases as us that shorten our lives and reduce our reproductive fitness. In other words, epigenetic changes are not always beneficial and should be subject to natural selection.

This understanding of epigenetics has indeed challenged our understanding of inheritance, and with that, evolution.9 While the “modern synthesis of evolution” stated that evolution occurs by small genetic changes, that synthesis reflected our understanding of inheritance when it was developed in the 1930s and 40s. We must now add epigenetics to the repertoire of inheritance, and if epigenetic marks can be inherited, then they can also impact evolutionary change.10 It is worth noting that Darwin proposed evolution without even knowing that DNA was the heritable material. Epigenetics certainly makes things more complicated, but it has not led to the end of evolutionary theory.

Orphan Genes

Orphan genes are an interesting development of recent years. Not that they have developed in recent years. Rather, they have only been recognized in recent years. Scientists love to investigate similarities. If a human gene has an ortholog (the same gene in another species) in the fruit fly, for example, then it is often easier to investigate the function of that gene in the fruit fly.  Humans are difficult to dissect and experiment on (for obvious reasons). Fruit flies are insects for which few people have emotional attachment. Many scientists have spent their time investigating this “low-hanging fruit,” those genes that are easy to study in lower organisms, ignoring the so-called orphan genes which do not have orthologs in other organisms.

There are many candidates for orphan gene status, although few genes have evidence to back up their orphan status. Chadwick and Brand state that “more than 1,000 orphan genes are recognized in humans.” This number likely comes from a 2007 publication in which genes found only in the human lineage, but not in the mouse or dog, are investigated for their functionality as protein-coding genes.11 This study identifies 1177 potential orphan genes, of which none are found to be likely genes in our close relative, the chimpanzee. Following a number of technical analyses, they suggest that none of these have characteristics of protein coding genes, although 12 have been shown in the literature to produce a protein. Hence, it could be that some of the remaining potential orphans are true protein coding genes. Due to highly sensitive mass spectrometry methods currently used to analyze the proteome, it is unlikely that all of these putative orphan genes are true protein coding genes. Without evidence, they are certainly not recognized by the scientific community.

Chadwick and Brand ask, “Where did these orphan genes come from?” They suggest that God put them there, and that scientists are stumped by the discovery of orphan genes.  I agree that God may have put them there, but I also know that scientists have given this much thought and have come up with many ways through which God may have put them there (although saying that God put them there would not fall in the realm of naturalistic science). One human-specific gene mentioned by Chadwick and Brand, ARHGAP11B, is thought to be important for the large brain of humans. The scientific report on this discovery states that ARHGAP11B arose as a duplication of ARHGAP11A gene, which is found throughout the animal kingdom.12 Gene duplication is a well-documented occurrence that would seem to disqualify this gene as an orphan—it seems that it does have a parent. Other orphan genes have been shown to arise through the mutation of non-coding sequence. For example, a simple one-base-pair deletion event can result in the change of reading frame of a gene so that it produces an actual protein of some length in humans that is not found in the chimpanzee lineage.13 It is clear that scientists have given the origin of orphan genes much thought, and have come up with some good explanations for their origin. It is unlikely that orphan genes will pose much challenge to evolution.

Macroevolution

To conclude, I would like to consider the theme of macroevolution as used in the title of this piece—if macroevolution is left dangling, we should have a definition for macroevolution that clarifies how it differs from other forms of evolution that are more accepted. The terms macroevolution and microevolution are commonly tossed about, sometimes within regular scientific circles, but frequently within young-earth creationist circles to suggest that there is a sharp divide between macroevolution, the generation of new species (or genera, or families, or orders), and smaller adaptations that allow a moth to adapt to sooty buildings or a finch to adapt to drier conditions. But where exactly does the division lie between macroevolution and microevolution?

Maybe our current knowledge of genomes can help us with identifying the dividing line between macroevolution and microevolution. For example, we know that the difference between you and me, at the level of our genetic code, is about 0.1%. That means that I differ from you at about 1 in every 1000 DNA bases. Clearly this is acceptable as microevolution. We might also allow for the radiation of many dog-like species since the flood. Many people allow for representatives of a taxonomic family to have been present on Noah’s ark, suggesting that any change beyond the family level is microevolution. The first Adventist biologist with a doctoral degree, Frank Marsh, is thought to have first suggested this idea. If we consider the dog family, Canidae (coyotes, dogs, foxes, jackals, and wolves), for example, the difference in mitochondrial DNA sequence between the dog and the red fox is about 15%.14 This is roughly twice that between humans and chimps.

Of course, the similarity between humans and chimps is a sensitive topic. While we are likely to be somewhat comfortable with a possible relationship (microevolution) between non-human members of the great ape family, we are unlikely to be comfortable with the close relationship between us and other great apes. Incidentally, based on genomic data, the chimpanzee and the orangutan are less similar to each other than we are to the chimpanzee.15 This is just one instance in which genome science presents a challenge to a traditional young-earth understanding.

Chadwick and Brand not unexpectedly underestimate the genome similarities between humans and chimps when they state that we share “up to 96 percent” of our protein coding genes with the chimpanzee. The real facts can be found in the scientific literature.16 Humans differ from chimpanzees at approximately 35 million nucleotide positions, out of a total genome size of approximately 3 billion for both humans and chimps. This is about a 1% difference (99% similarity) at the level of single nucleotide changes. In addition, humans and chimps differ due to about 5 million insertion and deletion events that result in another 90 million nucleotide differences—gaps in either genome. These 90 million differences plus the previous 35 million total to 125 million—about a 4% difference (96% similarity). However, if we look only at the protein coding genes, these differ at only about 3 million nucleotide positions—a 0.1% difference (99.9% similarity) in protein coding genes. To be more accurate, Chadwick and Brand should have stated “up to 99.9 percent” similarity in protein-coding genes when comparing the human and chimpanzee genomes. But this is likely to make us uncomfortable.

To be sure, recent genome science is challenging. Our genomes are complicated in many ways, and I’m sure that there are more surprises to come. Through all of these surprises, however, a close reading of the scientific literature suggests that evolutionary theory is not on life support. In fact, an evolutionary interpretation is often the simplest way to interpret discoveries in genome science, from the relationships of organisms, to the role of epigenetics, and the rise of new genes within genomes. Genome research can aid in paternity disputes, can solve crime, can clarify ancestry, and can help to predict health issues. These same methods of studying our genomes can also suggest deeper relationships that may extend past the last hundred or thousand years to ages past. I believe that it is important to be clear about the challenges that arise from these studies, and to make people aware of the challenges posed in both directions. It is also important for our Adventist scientists to be sure that they get the facts straight and do not over-exaggerate the implications. The reputation of our church is at stake here. Finally, the simplest reading of the Bible is one that is not encumbered with modern science but one that reads it as a plan for the salvation of man regardless of whether man has been here for six thousand or one hundred thousand years.

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NOTES:

1. Denton, M. Evolution: a theory in crisis. 1st U.S. edn,  (Adler & Adler, 1986).

2. Bassuk, A. G., Zheng, A., Li, Y., Tsang, S. H. & Mahajan, V. B. Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells. Scientific reports 6, 19969, doi:10.1038/srep19969 (2016).

3. Porteus, M. Genome Editing: A New Approach to Human Therapeutics. Annual review of pharmacology and toxicology 56, 163-190, doi:10.1146/annurev-pharmtox-010814-124454 (2016).

4. Berget, S. M., Moore, C. & Sharp, P. A. Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Proceedings of the National Academy of Sciences of the United States of America 74, 3171-3175 (1977).

5. Barbosa-Morais, N. L. et al. The evolutionary landscape of alternative splicing in vertebrate species. Science 338, 1587-1593, doi:10.1126/science.1230612 (2012).

6. Brosius, J. & Gould, S. J. On "genomenclature": a comprehensive (and respectful) taxonomy for pseudogenes and other "junk DNA". Proceedings of the National Academy of Sciences of the United States of America 89, 10706-10710 (1992).

7. Kellis, M. et al. Defining functional DNA elements in the human genome. Proceedings of the National Academy of Sciences of the United States of America 111, 6131-6138, doi:10.1073/pnas.1318948111 (2014).

8. Ost, A. et al. Paternal diet defines offspring chromatin state and intergenerational obesity. Cell 159, 1352-1364, doi:10.1016/j.cell.2014.11.005 (2014).

9. Danchin, E. et al. Beyond DNA: integrating inclusive inheritance into an extended theory of evolution. Nature reviews. Genetics 12, 475-486, doi:10.1038/nrg3028 (2011).

10. Hernando-Herraez, I., Garcia-Perez, R., Sharp, A. J. & Marques-Bonet, T. DNA Methylation: Insights into Human Evolution. PLoS genetics 11, e1005661, doi:10.1371/journal.pgen.1005661 (2015).

11. Clamp, M. et al. Distinguishing protein-coding and noncoding genes in the human genome. Proceedings of the National Academy of Sciences of the United States of America 104, 19428-19433, doi:10.1073/pnas.0709013104 (2007).

12. Florio, M. et al. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science 347, 1465-1470, doi:10.1126/science.aaa1975 (2015).

13. Knowles, D. G. & McLysaght, A. Recent de novo origin of human protein-coding genes. Genome research 19, 1752-1759, doi:10.1101/gr.095026.109 (2009).

14. Zhong, H. M., Zhang, H. H., Sha, W. L., Zhang, C. D. & Chen, Y. C. Complete Mitochondrial Genome of the Red Fox (Vuples vuples) and Phylogenetic Analysis with Other Canid Species. Zoological research 31, 122-130, doi:10.3724/SP.J.1141.2010.02122 (2010).

15. Scally, A. et al. Insights into hominid evolution from the gorilla genome sequence. Nature 483, 169-175, doi:10.1038/nature10842 (2012).

16. Mikkelsen, T. S. et al. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69-87, doi:10.1038/nature04072 (2005).

The author is an Adventist scientist and educator with a PhD in the biological sciences. He believes that we must be as accurate and honest as possible in all things, both scientific and religious, even when they make us uncomfortable. However, he does not feel at liberty to disclose his name. Jon Johnson is a pseudonym.

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