Yeast Gene Editing Study Raises Questions about the Evolutionary Origin of Human Chromosome 2

yeastgeneediting

BY FAZALE RANA – SEPTEMBER 12, 2018

As a biochemist and a skeptic of the evolutionary paradigm, people often ask me two interrelated questions:

  1. What do you think are the greatest scientific challenges to the evolutionary paradigm?
  2. How do you respond to all the compelling evidence for biological evolution?

When it comes to the second question, people almost always ask about the genetic similarity between humans and chimpanzees. Unexpectedly, new research on gene editing in brewer’s yeast helps answer these questions more definitively than ever.

For many people, the genetic comparisons between the two species convince them that human evolution is true. Presumably, the shared genetic features in the human and chimpanzee genomes reflect the species’ shared evolutionary ancestry.

One high-profile example of these similarities is the structural features human chromosome 2 shares with two chimpanzee chromosomes labeled chromosome 2A and chromosome 2B. When the two chimpanzee chromosomes are placed end to end, they look remarkably like human chromosome 2. Evolutionary biologists interpret this genetic similarity as evidence that human chromosome 2 arose when chromosome 2A and chromosome 2B underwent an end-to-end fusion. They claim that this fusion took place in the human evolutionary lineage at some point after it separated from the lineage that led to chimpanzees and bonobos. Therefore, the similarity in these chromosomes provides strong evidence that humans and chimpanzees share an evolutionary ancestry.

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Figure 1: Human and Chimpanzee Chromosomes Compared

Image credit: Who Was Adam? (Covina, CA: RTB Press, 2015), p. 210.

Yet, new work by two separate teams of synthetic biologists from the United States and China, respectively, raises questions about this evolutionary scenario. Working independently, both research teams devised similar gene editing techniques that, in turn, they used to fuse the chromosomes in the yeast species, Saccharomyces cerevisiae (brewer’s yeast).Their work demonstrates the central role intelligent agency must play in end-on-end chromosome fusion, thereby countering the evolutionary explanation while supporting a creation model interpretation of human chromosome 2.

The Structure of Human Chromosome 2

Chromosomes are large structures visible in the nucleus during the cell division process. These structures consist of DNA combined with proteins to form the chromosome’s highly condensed, hierarchical architecture.

yeast-gene-editing-study-2Figure 2: Chromosome Structure

Image credit: Shutterstock

Each species has a characteristic number of chromosomes that differ in size and shape. For example, humans have 46 chromosomes (23 pairs); chimpanzees and other apes have 48 (24 pairs).

When exposed to certain dyes, chromosomes stain. This staining process produces a pattern of bands along the length of the chromosome that is diagnostic. The bands vary in number, location, thickness, and intensity. And the unique banding profile of each chromosome helps geneticists identify them under a microscope.

In the early 1980s, evolutionary biologists compared the chromosomes of humans, chimpanzees, gorillas, and orangutans for the first time.2 These studies revealed an exceptional degree of similarity between human and chimp chromosomes. When aligned, the human and corresponding chimpanzee chromosomes display near-identical banding patterns, band locations, band size, and band stain intensity. To evolutionary biologists, this resemblance reveals powerful evidence for human and chimpanzee shared ancestry.

The most noticeable difference between human and chimp chromosomes is the quantity: 46 for humans and 48 for chimpanzees. As I pointed out, evolutionary biologists account for this difference by suggesting that two chimp chromosomes (2A and 2B) fused. This fusion event would have reduced the number of chromosome pairs from 24 to 23, and the chromosome number from 48 to 46.

As noted, evidence for this fusion comes from the close similarity of the banding patterns for human chromosome 2 and chimp chromosomes 2A and 2B when the two are oriented end on end. The case for fusion also gains support by the presence of: (1) two centromeres in human chromosome 2, one functional, the other inactive; and (2) an internal telomeresequence within human chromosome 2.3 The location of the two centromeres and internal telomere sequences corresponds to the expected locations if, indeed, human chromosome 2 arose as a fusion event.4

Evidence for Evolution or Creation?

Even though human chromosome 2 looks like it is a fusion product, it seems unlikely to me that its genesis resulted from undirected natural processes. Instead, I would argue that a Creator intervened to create human chromosome 2 because combining chromosomes 2A and 2B end to end to form it would have required a succession of highly improbable events.

I describe the challenges to the evolutionary explanation in some detail in a previous article:

  • End-to-end fusion of two chromosomes at the telomeres faces nearly insurmountable hurdles.
  • And, if somehow the fusion did occur, it would alter the number of chromosomes and lead to one of three possible scenarios: (1) nonviable offspring, (2) viable offspring that suffers from a diseased state, or (3) viable but infertile offspring. Each of these scenarios would prevent the fused chromosome from entering and becoming entrenched in the human gene pool.
  • Finally, if chromosome fusion took place and if the fused chromosome could be passed on to offspring, the event would have had to create such a large evolutionary advantage that it would rapidly sweep through the population, becoming fixed.

This succession of highly unlikely events makes more sense, from my vantage point, if we view the structure of human chromosome 2 as the handiwork of a Creator instead of the outworking of evolutionary processes. But why would these chromosomes appear to be so similar, if they were created? As I discuss elsewhere, I think the similarity between human and chimpanzee chromosomes reflects shared design, not shared evolutionary ancestry. (For more details, see my article “Chromosome 2: The Best Evidence for Evolution?”)

Yeast Chromosome Studies Offer Insight

Recent work by two independent teams of synthetic biologists from the US and China corroborates my critique of the evolutionary explanation for human chromosome 2. Working within the context of the evolutionary framework, both teams were interested in understanding the influence that chromosome number and organization have on an organism’s biology and how chromosome fusion shapes evolutionary history. To pursue this insight, both research groups carried out similar experiments using CRISPR/Cas9 gene editing to reduce the number of chromosomes in brewer’s yeast from 16 to 1 (for the Chinese team) and from 16 to 2 (for the team from the US) through a succession of fusion events.

Both teams reduced the number of chromosomes in stages by fusing pairs of chromosomes. The first attempt reduced the number from 16 to 8. In the next round they fused pairs of the newly created chromosome to reduce the number from 8 to 4, and so on.

To their surprise, the yeast seemed to tolerate this radical genome editing quite well—although their growth rate slowed and the yeast failed to thrive under certain laboratory conditions. Gene expression was altered in the modified yeast genomes, but only for a few genes. Most of the 5,800 genes in the brewer’s yeast genome were normally expressed, compared to the wild-type strain.

For synthetic biology, this work is a milestone. It currently stands as one of the most radical genome reconfigurations ever achieved. This discovery creates an exciting new research tool to address fundamental questions about chromosome biology. It also may have important applications in biotechnology.

The experiment also ranks as a milestone for the RTB human origins creation model because it helps address questions about the origin of human chromosome 2. Specifically, the work with brewer’s yeast provides empirical evidence that human chromosome 2 must have been shaped by an Intelligent Agent. This research also reinforces my concerns about the capacity of evolutionary mechanisms to generate human chromosome 2 via the fusion of chimpanzee chromosomes 2A and 2B.

Chromosome fusion demonstrates the critical role intelligent agency plays.

Both research teams had to carefully design the gene editing system they used so that it would precisely delete two distinct regions in the chromosomes. This process affected end-on-end chromosome fusions in a way that would allow the yeast cells to survive. Specifically, they had to delete regions of the chromosomes near the telomeres, including the highly repetitive telomere-associated sequences. While they carried out this deletion, they carefully avoided deleting DNA sequences near the telomeres that harbored genes. They also simultaneously deleted one of the centromeres of the fused chromosomes to ensure that the fused chromosome would properly replicate and segregate during cell division. Finally, they had to make sure that when the two chromosomes fused, the remaining centromere was positioned near the center of the resulting chromosome.

In addition to the high-precision gene editing, they had to carefully construct the sequence of donor DNA that accompanied the CRISPR/Cas9 gene editing package so that the chromosomes with the deleted telomeres could be directed to fuse end on end. Without the donor DNA, the fusion would have been haphazard.

In other words, to fuse the chromosomes so that the yeast survived, the research teams needed a detailed understanding of chromosome structure and biology and a strategy to use this knowledge to design precise gene editing protocols. Such planning would ensure that chromosome fusion occurred without the loss of key genetic information and without disrupting key processes such as DNA replication and chromosome segregation during cell division. The researchers’ painstaking effort is a far cry from the unguided, undirected, haphazard events that evolutionary biologists think caused the end-on-end chromosome fusion that created human chromosome 2. In fact, given the high-precision gene editing required to create fused chromosomes, it is hard to envision how evolutionary processes could ever produce a functional fused chromosome.

A discovery by both research teams further complicates the evolutionary explanation for the origin of human chromosome 2. Namely, the yeast cells could not replicate unless the centromere of one of the chromosomes was deleted at the time the chromosomes fused. The researchers learned that if this step was omitted, the fused chromosomes weren’t stable. Because centromeres serve as the point of attachment for the mitotic spindle, if a chromosome possesses two centromeres, mistakes occur in the chromosome segregation step during cell division.

It is interesting that human chromosome 2 has two centromeres but one of them has been inactivated. (In the evolutionary scenario, this inactivation would have happened through a series of mutations in the centromeric DNA sequences that accrued over time.) However, if human chromosome 2 resulted from the fusion of two chimpanzee chromosomes, the initial fusion product would have possessed two centromeres, both functional. In the evolutionary scenario, it would have taken millennia for one of the chromosomes to become inactivated. Yet, the yeast studies indicate that centromere loss must take place simultaneously with end-to-end fusion. However, based on the nature of evolutionary mechanisms, it cannot.

Chromosome fusion in yeast leads to a loss of fitness.

Perhaps one of the most remarkable outcomes of this work is the discovery that the yeast cells lived after undergoing that many successive chromosome fusions. In fact, experts in synthetic biology such as Gianni Liti (who commented on this work for Nature), expressed surprise that the yeast survived this radical genome restructuring.5

Though both research teams claimed that the fusion had little effect on the fitness of the yeast, the data suggests otherwise. The yeast cells with the fused chromosomes grew more slowly than wild-type cells and struggled to grow under certain culture conditions. In fact, when the Chinese research team cultured the yeast with the single fused chromosome with the wild-type strain, the wild-type yeast cells out-competed the cells with the fused chromosome.

Although researchers observed changes in gene expression only for a small number of genes, this result appears to be a bit misleading. The genes with changed expression patterns are normally located near telomeres. The activity of these genes is normally turned down low because they usually are needed only under specific growth conditions. But with the removal of telomeres in the fused chromosomes, these genes are no longer properly regulated; in fact, they may be over-expressed. And, as a consequence of chromosome fusion, some genes that normally reside at a distance from telomeres find themselves close to telomeres, leading to reduced activity.

This altered gene expression pattern helps explains the slower growth rate of the yeast strain with fused chromosomes and the yeast cells’ difficulty to grow under certain conditions. The finding also raises more questions about the evolutionary scenario for the origin of human chromosome 2. Based on the yeast studies, it seems reasonable to think that the end-to-end fusion of chromosomes 2A and 2B would have reduced the fitness of the offspring that first inherited the fused chromosome 2, making it less likely that the fusion would have taken hold in the human gene pool.

Chromosome fusion in yeast leads to a loss of fertility.

Normally, yeast cells reproduce asexually. But they can also reproduce sexually. When yeast cells mate, they fuse. As a result of this fusion event, the resulting cell has two sets of chromosomes. In this state, the yeast cells can divide or form spores. In many respects, the sexual reproduction of yeast cels resembles the sexual reproduction in humans, in which egg and sperm cells, each with one set of chromosomes, fuse to form a zygote with two sets of chromosomes.

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Figure 3: Yeast Cell Reproduction

Image credit: Shutterstock

Both research groups discovered that genetically engineered yeast cells with fused chromosomes could mate and form spores, but spore viability was lower than for wild-type yeast.

They also discovered that after the first round of chromosome fusion when the genetically engineered yeast possessed 8 chromosomes, mating normal yeast cells with those harboring fused chromosomes resulted in low fertility. When wild-type yeast cells were mated with yeast strains that had been subjected to additional rounds of chromosome fusion, spore formation failed altogether.

The synthetic biologists find this result encouraging because it means that if they use yeast with fused chromosomes for biotechnology applications, there is little chance that the genetically engineered yeast will mate with wild-type yeast. In other words, the loss of fertility serves as a safeguard.

However, this loss of fertility does not bode well for evolutionary explanations for the origin of human chromosome 2. The yeast studies indicate that chromosome fusion leads to a loss of fertility because of the mismatch in chromosome number, which makes it difficult for chromosomes to align and properly segregate during cell division. So, why wouldn’t this loss of fertility happen if chromosomes 2A and 2B fuse?

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Figure 4: Cell Division

Image credit: Shutterstock

In short, the theoretical concerns I expressed about the evolutionary origin of human chromosome 2 find experimental support in the yeast studies. And the indisputable role intelligent agency plays in designing and executing the protocols to fuse yeast chromosomes provides empirical evidence that a Creator must have intervened in some capacity to design human chromosome 2.

Of course, there are a number of outstanding questions that remain for a creation model interpretation of human chromosome 2, including:

  • Why would a Creator seemingly fuse together two chromosomes to create human chromosome 2?
  • Why does this chromosome possess internal telomere sequences?
  • Why does human chromosome 2 harbor seemingly nonfunctional centromere sequences?

We predict that as we learn more about the biology of human chromosome 2, we will discover a compelling rationale for the structural features of this chromosome, in a way that befits a Creator.

But, at this juncture the fusion of yeast chromosomes in the lab makes it hard to think that unguided evolutionary processes could ever successfully fuse two chromosomes, including human chromosome 2, end on end. Creation appears to make more sense.

Resources

Endnotes

  1. Jingchuan Luo et al., “Karyotype Engineering by Chromosome Fusion Leads to Reproductive Isolation in Yeast,” Nature 560 (2018): 392–96, doi:10.1038/s41586-018-0374-x; Yangyang Shao et al., “Creating a Functional Single-Chromosome Yeast,” Nature 560 (2018): 331–35, doi:10.1038/s41586-018-0382-x.
  2. Jorge J. Yunis, J. R. Sawyer, and K. Dunham, “The Striking Resemblance of High-Resolution G-Banded Chromosomes of Man and Chimpanzee,” Science 208 (1980): 1145–48, doi:10.1126/science.7375922; Jorge J. Yunis and Om Prakash, “The Origin of Man: A Chromosomal Pictorial Legacy,” Science 215 (1982): 1525–30, doi:10.1126/science.7063861.
  3. The centromere is a region of the DNA molecule near the center of the chromosome that serves as the point of attachment for the mitotic spindle during the cell division process. Telomeres are DNA sequences located at the tip ends of chromosomes designed to stabilize the chromosome and prevent it from undergoing degradation.
  4. J. W. Ijdo et al., “Origin of Human Chromosome 2: An Ancestral Telomere-Telomere Fusion,” Proceedings of the National Academy of Sciences USA 88 (1991): 9051–55, doi:10.1073/pnas.88.20.9051; Rosamaria Avarello et al., “Evidence for an Ancestral Alphoid Domain on the Long Arm of Human Chromosome 2,” Human Genetics 89 (1992): 247–49, doi:10.1007/BF00217134.
  5. Gianni Liti, “Yeast Chromosome Numbers Minimized Using Genome Editing,” Nature 560 (August 1, 2018): 317–18, doi:10.1038/d41586-018-05309-4.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2018/09/12/yeast-gene-editing-study-raises-questions-about-the-evolutionary-origin-of-human-chromosome-2

 

Did Neanderthals Self-Medicate?

neanderthalselfmedicate

BY FAZALE RANA – JANUARY 24, 2018

Calculus is hard.

But it is worth studying because it is such a powerful tool.

Oh, wait!

You don’t think I’m referring to math, do you? I’m not. I’m referring to dental calculus, the hardened plaque that forms on teeth.

Recently, researchers from Australia and the UK studied the calculus scraped from the teeth of Neanderthals and compared it to the calculus taken from the teeth of modern humans and chimpanzees (captured from the wild) with the hope of understanding the diets and behaviors of these hominins.1 The researchers concluded that this study supports the view that Neanderthals had advanced cognitive abilities like that of modern humans. If so, this conclusion creates questions and concerns about the credibility of the biblical view of humanity; specifically, the idea that we stand apart from all other creatures on Earth because we are uniquely made in God’s image. Ironically, careful assessment of this work actually supports the notion of human exceptionalism, and with it provides scientific evidence that human beings are made in God’s image.

This study built upon previous work in which researchers discovered that they could extract trace amounts of different types of compounds from the dental calculus of Neanderthals and garner insights about their dietary practices.2 Scientists have learned that when plaque forms, it traps food particles and microbes from the mouth and respiratory tract. In the most recent study, Australian and British scientists extracted ancient DNA from the plaque samples isolated from the teeth of Neanderthals recovered in Spy Cave (Belgium) and El Sidrón (Spain). These specimens age-date between 42,000 and 50,000 years in age. By sequencing the ancient DNA in the samples and comparing the sequences to known sequences in databases, the research team determined the types of food Neanderthals ate and the microorganisms that infected their mouths.

Neanderthal Diets

Based on the ancient DNA recovered from the calcified dental plaque, the researchers concluded that the Neanderthals unearthed at Spy Cave and El Sidrón consumed different diets. The calculus samples taken from the Spy Cave specimens harbored DNA from the woolly rhinoceros and European wild sheep. It also contained mushroom DNA. On the other hand, the ancient DNA samples taken from the dental plaque of the El Sidrón specimens came from pine nuts, moss, mushrooms, and tree bark. These results suggest that the Spy Neanderthals consumed a diet comprised largely of meat, while the El Sidrón hominins ate a vegetarian diet.

The microbial DNA recovered from the dental calculus confirmed the dietary differences between the two Neanderthal groups. In Neanderthals, and in modern humans, the composition of the microbiota in the mouth is dictated in part by the diet, varying in predictable ways for meat-based and plant-based diets, respectively.

Did Neanderthals Consume Medicinal Plants?

One of the Neanderthals from El Sidrón—a teenage boy—had a large dental abscess. The researchers recovered DNA from his dental calculus showing that he also suffered from a gut parasite that causes diarrhea. But, instead of suffering without any relief, it looks as if this sick individual was consuming plants with medicinal properties. Researchers recovered DNA from poplar plants, which produce salicylic acid, a painkiller, and DNA from a fungus that produces penicillin, an antibiotic. Interestingly, the other El Sidrón specimen showed no evidence of ancient DNA from poplar or the fungus, Penicillium.

If Neanderthals were able to self-medicate, the researchers conclude that these hominins must have had advanced cognitive abilities, similar to those of modern humans. One of the members of the research team, Alan Cooper, muses, “Apparently, Neandertals possessed a good knowledge of medicinal plants and their various anti-inflammatory and pain-relieving properties, and seem to be self-medicating. The use of antibiotics would be very surprising, as this is more than 40,000 years before we developed penicillin. Certainly, our findings contrast markedly with the rather simplistic view of our ancient relatives in popular imagination.”3

Though intriguing, one could argue that the research team’s conclusion about Neanderthals self-medicating is a bit of an overreach, particularly the idea that Neanderthals were consuming a specific fungus as a source of antibiotics. Given that the El Sidrón Neanderthals were eating a vegetarian diet, it isn’t surprising that they occasionally consumed fungus because Penicillium grows naturally on plant material when it becomes moldy. This conclusion is based on a single Neanderthal specimen; thus, it could simply be a coincidence that the sick Neanderthal teenager consumed the fungus. In fact, it would be virtually impossible for Neanderthals to intentionally eat penicillin-producing fungi because, according to anthropologist Hannah O’Regan from the University of Nottingham, “It’s difficult to tell these specific moulds apart unless you have a hand lens.”4

Zoopharmacognosy

But even if Neanderthals were self-medicating, this behavior is not as remarkable as it might initially seem. Many animals self-medicate. In fact, this phenomenon is called zoopharmacognosy.5 For example, chimpanzees will consume the leaves of certain plants to make themselves vomit, in order to rid themselves of intestinal parasites. So, instead of viewing the consumption of poplar plants and fungus by Neanderthals as evidence for advanced behavior, perhaps, it would be better to regard it as one more instance of zoopharmacognosy.

Medicine and Human Exceptionalism

The difference between the development and use of medicine by modern humans and the use of medicinal plants by Neanderthals (assuming they did employ plants for medicinal purposes) is staggering. Neanderthals existed on Earth longer than modern humans have. And at the point of their extinction, the best that these creatures could do is incorporate into their diets a few plants that produced compounds that were natural painkillers or antibiotics. On the other hand, though on Earth for only around 150,000 years, modern humans have created an industrial-pharmaceutical complex that routinely develops and dispenses medicines based on a detailed understanding of chemistry and biology.

As paleoanthropologist Ian Tattersall and linguist Noam Chomsky (along with other collaborators) put it:

“Our species was born in a technologically archaic context . . . . Then, within a remarkably short space of time, art was invented, cities were born, and people had reached the moon.”6

And biomedical advance has yielded an unimaginably large number of drugs that improve the quality of our lives. In other words, comparing the trajectories of Neanderthal and modern human technologies highlights profound differences between us—differences that affirm modern humans really are exceptional, echoing the biblical view that human beings are truly made in God’s image.

Resources

Endnotes

  1. Laura S. Weyrich et al., “Neanderthal Behavior, Diet, and Disease Inferred from Ancient DNA in Dental Calculus,” Nature 544 (April 20, 2017): 357–61, doi:10.1038/nature21674.
  2. Karen Hardy et al., “Neanderthal Medics? Evidence for Food, Cooking, and Medicinal Plants Entrapped in Dental Calculus,” Naturwissenschaften 99 (August 2012): 617–26, doi:10.1007/s00114-012-0942-0.
  3. “Dental Plaque DNA Shows Neandertals Used ‘Aspirin,’” Phys.org, updated March 8, 2017, https://phys.org/print408199421.html.
  4. Colin Barras, “Neanderthals May Have Medicated with Penicillin and Painkillers,” New Scientist, March 8, 2017, https://www.newscientist.com/article/2123669-neanderthals-may-have-medicated-with-penicillin-and-painkillers/.
  5. Shrivastava Rounak et al, “Zoopharmacognosy (Animal Self Medication): A Review,” International Journal of Research in Ayurveda and Pharmacy 2 (2011): 1510–12.
  6. Johan J. Bolhuis et al., “How Could Language Have Evolved?,” PLoS Biology 12 (August 26, 2014): e1001934, doi:10.1371/journal.pbio.1001934.
Reprinted with permission by the author
Original Article:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2018/01/24/did-neanderthals-self-medicate