"Evolutionary theorists", the study of the history of life, and practical applications in medical biology

Resident ID proponents I wont name to protect their brittle egoes are again implying that the study of evolution by “evolutionary theorists” has no practical application in stuff like medical research.

This reflects a common view out there among creationists (gleefully fabricated and regurgitated by many ID propagandizers) that evolution is this entirely imaginary field where evolutionary biologists just dream up histories for life that never occurred in reality.

A frequent example is that inferring evolutionary histories (phylogenetic trees) from data is basically just like arbitrarily drawing lines on paper between things and then telling those dreaded “just so stories”. Disregarding the hypocricy of such an accusation (because ID-creationism is one giant just-so story) I think we would do well to ask if that is actually true?

Well there’s a new review article out in the Journal of Molecular Evolution on one of my favorite topics. That’s right, it’s a Ancestral Sequence Reconstruction again:

Abstract

As both a computational and an experimental endeavor, ancestral sequence reconstruction remains a timely and important technique. Modern approaches to conduct ancestral sequence reconstruction for proteins are built upon a conceptual framework from journal founder Emile Zuckerkandl. On top of this, work on maximum likelihood phylogenetics published in Journal of Molecular Evolution in 1996 was one of the first approaches for generating maximum likelihood ancestral sequences of proteins. From its computational history, future model development needs as well as potential applications in areas as diverse as computational systems biology, molecular community ecology, infectious disease therapeutics and other biomedical applications, and biotechnology are discussed. From its past in this journal, there is a bright future for ancestral sequence reconstruction in the field of evolutionary biology.

Ancestral Sequence Reconstruction and Infectious Disease

Ancestral sequence reconstruction can be used to understand viral evolution and towards therapeutic applications (Arenas 2020). An understanding of the evolutionary histories of these viruses can lead to applications in detecting targeted regions for future therapeutics, and to assist in predicting new viral resistance against current drugs.

Ancestral sequence reconstruction is also of emerging interest for vaccine technologies, especially for the development of vaccines to combat rapidly evolving viruses such as HIV and influenza strains (Gaschen et al. 2002; Ducatez et al. 2011). Using ancestrally derived sequences to create vaccine reagents takes advantage of the evolutionary history of the virus. This strategy contrasts with other methods which construct a consensus sequence from different viral strains, ignoring phylogenetic structure. A vaccine reagent can be based on the last common ancestral sequence of all the strains that are circulating, or from other points in the tree. For example, when the phylogenetic topology is skewed, the “center of tree” method may be implemented. The center of tree method considers the ancestral sequence that minimizes the evolutionary distance between different viral strains of interest (Nickle et al. 2003).

In the age of the SARS-CoV-2, ancestral sequence reconstruction has become of immediate interest to assist in vaccine development (Zhou et al. 2020). Like the rapidly evolving RNA virus influenza and retrovirus HIV, SARS-CoV-2 is also an RNA virus. However, a recent study used ancestral sequence reconstruction to demonstrate that unlike other RNA viruses, mutations in SARS-CoV-2 are rare, as the evolution rate is slower than the transmission rate. Because of the slow evolution of SARS-CoV-2, only one vaccine candidate may be necessary to match all currently circulating SARS-CoV-2 variants (Dearlove et al. 2020).

Aside from disease causing viruses, viruses are also developed to serve as a vehicle for gene therapy (Ivics et al. 1997). The Adeno-associated Virus (AAV) has been considered an efficient gene therapy for both inherited and infectious diseases. However, the complex structure and diversity associated with different target receptor binding for AAV make the virus difficult to properly structurally assemble when designed. Using ancestral sequence reconstruction, Zinn et al. (2015) were able to provide a virus with a structure that would remain evolutionarily resilient to future mutations and maintain broad clinical applicability.

Biomedical and Biotechnological Directions for Ancient Proteins

In addition to all the insights ASR reveals about natural evolutionary processes, it turns out that ancient proteins also have applied functions in biotechnology and biomedicine (Randall et al. 2016). Ancestral variants have been used to develop clinical treatments for type 2 diabetes (Skovgaard et al. 2006), gout (Kratzer et al. 2014), hemophilia (Zakas et al. 2017), tyrosinemia (Hendrikse et al. 2020) and others. It is anticipated that this trend in biomedicine will continue as ASR generates proteins having expanded biomolecular functionalities with lower immunogenic responses in human patients compared to their modern protein counterparts. Further, ancestral variants are being used in the biotechnology sector due to their unique and desirable properties. Companies such as nanoGUNE (Manteca et al. 2017), Syngenta, New England Biolabs (Zhou et al. 2012), DuPont (Ladics et al. 2020) and others have developed or integrated ancient proteins into their biotechnology product development pipelines, while some ancient proteins have even been tested for their value in the cosmetic industry (Perez-Jimenez et al. 2011).

The irony of ancient proteins having an applied utility to the development of therapeutics and industrial enzymes is clear. It is reasonable to expect that this utility will expand within the public and private sectors as more examples are discovered in the coming years. Sometimes one must explore the past in order to navigate the future.

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but this is probably true. suppose that evolution is false. do you think we would not produce drugs because of this? the answer is of course that we can still produce drugs even if evolution is false, and thus evolution is irrelevant to make a medicine.

Goalpost move detected.

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Dude how are you even alive?

We can cut down trees without the use of a saw or an axe, but that doesn’t mean the use of saws and axes is irrelevant to cutting down trees.

Do I need to tie your shoelaces next?

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so you are saying that evolution theory might improve the way we are making medicine? i dont think its true either. for instance: evolution does not predict what the ancient sequence would have looked like. some scientists even believe that we might had multiple origins of life.

It already is doing that. Examples of how are right there in the article I linked.

That’s exactly what it does. From extant gene sequences can ancestral sequences be inferred with phylogenetic methods. They can then be recreated in the laboratory and tested for function. And those functions can be useful in medicine and in biotechnology.

It is not relevant how many times life originated to whether ASR has practical applications in medical and biotechnological research and product development. It could be one, five, or two hundred times. As long as some species share common descent, ancestral states in their relationships can be inferred among them.

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but this is the problem: you first make this research and then get the conclusion, so this isnt realy an evolutionery prediction. even if all creatures were created by design we can get to the same conclusion.

It seems to me that only on evolution do we have an expectation that ancestral states on a phylogenetic tree should be functional and have practical application.

Why should ancestral nodes inferred on a phylogenetic tree yield functional biological molecules on design if those ancestral nodes do not correspond to molecules that really once existed?

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they indeed existed, if all creatures were almost identical in their initial creation state, which is not so different from the current state (chimp and human for instance have almost identical genomes).

This is a bit like saying that, because we have a dictionary to explain the meaning of words, we can throw away all of our books, since the dictionary can explain any words within those books.

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I could say that I was dumbfounded by this. But I wasn’t. I’ve seen this before from creationists. In this case, the “ID proponents I wont name to protect their brittle ego” denies that he is a creationist.

The implication of what he said, was that we never needed the Wright Brothers. All we need is a pilot to fly the plane.

Yes, that’s a stark analogy, and he will deny that. But it is the same problem of not seeing the relatedness of all science. Darwin set the ball rolling for an investigation of heritability of traits. And that’s the research program that has paid off here.

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That makes literally no sense. Their current state is not “almost identical”, so it makes no sense to say it is “not so different” from their initial state. Now regardless of how you adjust the “not so different” and “almost identical” values up and down you’re going to have to explain why that should result in a nested hierarchy, which you have failed to do innumerable times.

Moreover, you need to explain why an explicit model of molecular evolution (the substitution models used in likelihood and bayesian-based molecular phylogenies you insist aren’t real) should be able to reliably infer those “almost identical genomes” in the first place. If extant genomes did not evolve by accumulating mutations on branching lineages of descent, why does a method explicitly built on that assumption faithfully reproduce the originally but indendently created-to-be-nearly-identical gene sequences?

I realize that you’ve now completely lost comprehension of the subject, so I am of course only asking rhetorically for the benefit of people who are still able to think and keep up.

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realy? human and chimp arent almost identical in their genetic similarity?

first, i didnt said i reject phylogeny. i just reject the conclusion of that (nested hierarchy= common descent). second, as i said: we can get to the same conclusion even if all creatures were created almost identical to each other. thus, there is no difference between evolution and creation models in this case. as i said in my first comment, we can make medicines even if evolution is wrong. if you agree with that then i rest my case.

Yes, you have said that frequently, but it isn’t true. What you describe would result in a star phylogeny, not a resolved tree. You are just wrong about that. In phylogenetic terms, you are talking about explaining terminal branches when you should be thinking about explaining internal branches.

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a possible explanation is that some amino acids were under selection pressure. thus we dont get a star phylogeny. other possible explanation is that some amino acids were different in their creation state. in addition, we can get a nested hiearchy even under a wrong phylogeny (for instance a phylogeny which is base on morphology). so maybe the nested hierarchy argument by itself is wrong.

Excuse me for butting in, but this seems to me to be a silly thing to argue about. Why wouldn’t all types of creationists and anyone else agree that this type of research is useful? I myself not opposed to the word “evolution” - obviously this type of change over time obviously exists. We would all agree it’s empirical. I don’t see the point in arguing over semantics and I think it hurts creationism to argue over obvious empirical evidence when that’s what we emphasize all the time!

Wouldn’t it be more helpful to name the person and see if the actually disagree that this specific type of theorizing and research is useful?

Sorry, but selection pressure doesn’t predict a nested hierarchy. Nor does it predict that the same patter will be seen in silent sites and sites outside protein-coding exons.

It isn’t clear what you’re trying to say, I presume not even to you.

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Because it being useful now leaves them in the position of having to come up with an explanation for why a research paradigm they think is ultimately based on a falsehood somehow manages to improve and support related fields of science such as medicine. It doesn’t fit into their narrative. And that narrative about evolution being useless stamp-collecting of no practical benefit is a very common one.

Right, but we’re not just talking about “change over time”. Many of the reconstructed ancestral molecules would not have existed for millions of years, and some of them come from ancestors that simply shouldn’t exist according to proponents of independent creation.

The very same methods that are used to reconstruct relatively recent ancestral genes (such as those from viruses decades or hundreds of years old) are also used to reconstruct genes from the common ancestor of all primates including humans, the common ancestor of all mammals, or all amniotes, or vertebrates, or animals, or eukaryotes. And so on. These reconstructed genes now represent entities that independent creation says shouldn’t even exist. And yet they can be reconstructed and shown to work, and often times so well that they have practical application in both medicine and biotechnology. Why is this possible?

No I don’t think there’s any use in inviting that person to pretend s/he never meant to imply this particular research was useless. They are of course always speaking in vague generalities so can always just say they didn’t mean this thing in particular but some other evolution-research instead.

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I probably won’t have an answer as to why, but I’d be interested in the papers if you have time to link.

im not sure i got your point. i do accept that we can see variations among living species (such as the variations we see among dogs). but as you already know, we dont have empirical evidence that a dog can evolve into a species which isnt a dog. my point to Rumraket is that even if evolution is false, we can still make medicine. so evolution is irrelevant for making a medicine.

why not? if about half of the protein sequence was under selection pressure we could see a nested hierarchy. and you assume that the non-coding regions are non functional.

take this instance:

(image form Chapter 32 Class Presentation )

at least one of these nested hierarchy is wrong. so we can get a nested hierarchy even if we have a false nested hierarchy. thus a nested hierarchy cant support common descent.