Did Darwin get anything correct and what did Darwin get wrong?

[beaglelady]

@amkleinman

Should Darwin’s ideas be tossed out because he was wrong about universal common descent when his other ideas explain how drug resistance evolves?

That would be ridiculous. He was wrong about some things and had no knowledge of genetics. But he lived a long time ago, and the theory of evolution is constantly being tested, developed, and refined. That’s what makes it a robust scientific theory. On the other hand, pseudo-scientific ideas, like Intelligent Design and astrology, make no progress.

[amkleinman (Alan Kleinman)]

@wbwane

Two things. First, Darwin reported data and developed ideas from those data. He is not an end point, nor a starting point. Many of his ideas are based on the statements from the Reverend Thomas Malthus. It is a stream of thought and that Darwin got some things wrong is normal and natural in the development of ideas. Second, why to people from Kenya keep winning the Boston Marathon?

Which of Darwin’s ideas are supported by experimental evidence?

Do you equate being a fast runner with reproductive fitness? If so, why isn’t the population of Kenya greater than the population of China or India?

[amkleinman (Alan Kleinman)]

How does a lineage accumulate a set of adaptive mutations?

@rsewell

One at a time?

That is usually the case. The reason it isn’t two or more at a time is that they are random events. The joint probability of random events occurring is computed using the multiplication rule. That is why it takes a billion replications for each adaptive step in the Kishony and Lenski experiments. It works the same way for eukaryotes.

@rsewell

Fitness is contextual to environment, and at some point that diverged between humans and chimpanzees. Humans are enormously successful due to the unique capacity to manage and regulate environmental factors, and therefore reduce coupling to environmental constraints.

If you claim that humans and chimpanzees descended from a common ancestor, what mutations give humans that unique capacity to manage and regulate environmental factors?

[amkleinman (Alan Kleinman)]

@Nobby

Charles Darwin made significant contributions to the field of biology with his theory of evolution by natural selection. Many aspects of his work have been confirmed and expanded upon by subsequent scientific research. Here are some key points where Darwin was correct:

1. Descent with modification: Darwin proposed that species evolve over time and that all living organisms share a common ancestor. This idea has been strongly supported by evidence from multiple fields of biology, including genetics, paleontology, and comparative anatomy.
2. Natural selection: Darwin proposed that natural selection is the primary mechanism driving evolution. He argued that individuals with traits that are advantageous for their environment are more likely to survive and reproduce, passing on those traits to future generations. This concept has been validated by numerous studies and is widely accepted in the scientific community.
3. Adaptation: Darwin emphasized the importance of adaptation in evolution. He observed that organisms possess traits that are well-suited to their environments, which increase their chances of survival and reproductive success. This idea is supported by abundant evidence, such as the diverse adaptations found in different species.

Despite his many contributions, Darwin’s work also had some limitations and areas where he was not entirely correct:

1. Inheritance mechanism: Darwin lacked knowledge of the underlying mechanisms of inheritance. He proposed that traits were passed on through a blending mechanism, where offspring inherit a mix of traits from their parents. This idea was later replaced by Mendelian genetics, which explained inheritance through the discrete transmission of genes.
2. Incomplete understanding of heredity: Darwin was unaware of genes, DNA, and the molecular basis of heredity. These discoveries came after his time, and they provided a more detailed understanding of how traits are inherited and passed on to future generations.
3. Gradualism: Darwin proposed that evolution occurs gradually and continuously over long periods of time. While this idea holds true for many evolutionary changes, subsequent research has shown that some evolutionary events can happen relatively rapidly, through mechanisms such as punctuated equilibrium or rapid adaptation.

It’s important to note that science is an ongoing process, and Darwin’s ideas have been refined and expanded upon over the past century and a half. The modern understanding of evolution incorporates insights from genetics, molecular biology, palaeontology, and other fields, providing a more comprehensive and detailed understanding of the mechanisms and patterns of evolution.

Darwin made no attempt to mathematically model the patterns he was observing most likely because he had no idea of what DNA is. Natural selection has been experimentally verified. Do you understand how large a population is required for natural selection and adaptation to operate? Can you give any experimental evidence of punctuated equilibrium or “rapid adaptation”?

[T_aquaticus]

@amkleinman

The reason it isn’t two or more at a time is that they are random events. The joint probability of random events occurring is computed using the multiplication rule.

The multiplication rule does not apply in sexual populations. A mother with beneficial mutation A can mate with a father with beneficial mutation B, and some of their offspring will have both beneficial mutations.

[T_aquaticus]

@amkleinman

Descent with modification and adaptation works the same for eukaryotes as prokaryotes.

It doesn’t. Adaptation in asexual and sexual populations works differently. This is why experiments on asexual populations do not apply to sexual populations. This is why experiments comparing asexual and sexual populations show differences in how they adapt.

@amkleinman

Do you think that recombination can create new alleles?

In some certain circumstances, yes it can. If recombination occurs within a gene then a new allele can be created. Most of the time, it shuffles mutations between the two copies in each diploid genome in regions without genes. Offspring are then a combination of the haploid genomes from their father and mother. This means you can have two beneficial mutations that happen in different individuals which can then be combined in offspring further down the line. You don’t have to wait for two different mutations to happen in a direct lineage as you do in asexual populations.

[glipsnort (Steve Schaffner)]

@amkleinman

The joint probability of random events occurring is computed using the multiplication rule.

That’s correct (assuming the events are independent).

@amkleinman

That is why it takes a billion replications for each adaptive step in the Kishony and Lenski experiments.

That’s not correct. The bulk of the time required for each adaptive step is for the most fit current mutant (which may be one of many beneficial mutations in the current population) to become common enough in the population for it to be the likely background for a new beneficial mutation.

@amkleinman

It works the same way for eukaryotes.

As has already been explained to you, that is precisely wrong. In eukaryotes, recombination permits multiple beneficial mutations to occur and succeed in parallel, mixing and matching along the way to produce combinations of beneficial mutations. There is no need for the extended waiting period required for clonal bacteria.

@amkleinman

Do you understand how large a population is required for natural selection and adaptation to operate?

Yes, I do – I’ve done such modeling on multiple occasions. Have you? Please present your model.

@amkleinman

Can you give any experimental evidence of punctuated equilibrium or “rapid adaptation”?

There’s plenty of evidence, including experimental evidence, for rapid adaptation. (Whether it constitutes punctuated equilibrium or not is too subjective to be settled easily.) A classic study on the different rates of adaptation seen in experiments vs adaptive radiations vs very long-term evolution is “Rates of Evolution: Effects of Time and Temporal Scaling”, Philip Gingerich, Science 222:159-161.

[SkovandOfMitaze (Mi)]

I did not read everything, and so I’m not sure what all has been stated. But in addition to genetics we can also look at superimposed geological layers with a fossil record showing basal forms developing more and more divergent traits as speciation takes place. So we don’t see humans before the earliest primates. We don’t see primates before the earliest mammals. We don’t see mammals before the earliest tetrapods. We don’t see tetrapods before the earliest bony lunged fish which we don’t see before the earliest species of fish. The theory of evolution is overwhelmingly sound. Genetics further supports it. It does not detract from it. Geology supports it. It’s like a table with dozens of legs.

[amkleinman (Alan Kleinman)]

How do two or more possible adaptive mutations change the mathematics?

@T_aquaticus

If you have to ask this then you don’t understand your own mathematics.

If there are 1 million possible advantageous mutations it would obviously take fewer offspring to get an advantageous mutation than if there was only 1 possible advantageous mutation in the whole genome.

Do you think that each possible advantageous mutation puts that variant on the same evolutionary trajectory as any other variant? What happens for the next adaptive evolutionary step? Are there 1 million possible advantageous mutations for each variant? And for the next adaptive evolutionary step, are there 1 million possible advantageous mutations for each evolutionary trajectory?

@amkleinman

Does each of those variants follow the same evolutionary trajectory? Or do you now have two or more different lineages following different evolutionary trajectories?

@T_aquaticus

The population follows the same trajectory because they are all interbreeding.

Do Eskimos and Australian Aborigines have the same set of mutations?

@amkleinman

For example, HIV does recombination but 3-drug therapy still works. Why can’t HIV recombine adaptive mutations and defeat 3-drug combination therapy? Why do combination herbicides and pesticides work?

@T_Aquaticus

Drug resistance in HIV is not universally applicable to all species in all environments.

If you want to claim that humans could not evolve from a common ancestor shared with chimps then you need to show us the probabilities for humans, not HIV.

Why do you think that descent with modification and adaptation works differently for humans than for HIV, or for that matter, any other replicator? Humans when they replicate have offspring with random mutations, and HIV when it replicates has offspring with random mutations. Humans do recombination, HIV does recombination. If a human lineage is to adapt to a selection pressure, that lineage must accumulate a set of adaptive mutations. If an HIV lineage is to adapt to a selection pressure, that lineage must accumulate a set of adaptive mutations. Descent with modification and adaptation works the same for all replicators.

@amkleinman

Humans have had sufficient replications for mutations to occur at every possible site in the genome, but that’s a different matter than a lineage accumulating a set of adaptive mutations.

@T_aquaticus

If you are using asexual species as your model you are going to continue to get the wrong answers.

Why does 3-drug combination therapy work for the treatment of HIV despite the fact the virus does recombination? Why do combination selection pressures work for the control of weeds and insects despite the fact they are sexual replicators? Shouldn’t recombination cause this to fail?

@amkleinman

Do humans have greater reproductive fitness than chimpanzees and if so, what adaptive mutations do humans have that chimpanzees don’t have?

@T_aquaticus

Compare the genomes. Amongst those differences are the advantageous mutations that humans have. The same for chimps.

Why are there 8 billion humans and only 300,000 chimps? What adaptive mutations do humans have that give that reproductive difference?

@amkleinman

How does a lineage accumulate a set of adaptive mutations?

@T_aquaticus

That depends on whether the population is asexual or sexual.

We find that sex alters the molecular signatures of adaptation. We observe similar proportions of synonymous, nonsynonymous, and intergenic mutations segregating in sexual and asexual lines (Fig. 1b). Consistent with earlier work21, in asexual populations these types of mutation are roughly equally likely to fix, conditional on reaching observable frequency (Fig. 1b and Extended Data Table 3). This indicates that natural selection cannot efficiently distinguish between their effects. In contrast, fewer mutations fix in sexual populations, and these mutations are overwhelmingly nonsynonymous. These observations suggest that sex improves the efficiency of selection, so that only beneficial mutations fix.

To investigate how sex improves the efficiency of selection, we analysed the dynamics of adaptation. As in earlier studies21,22, asexual populations exhibit signatures of hitchhiking and clonal interference (Fig. 2a–d). Groups of functionally unrelated mutations, linked within the same genetic background, change in frequency together as clonal cohorts. The outcomes of evolution are determined by competition between these cohorts. In contrast, sexual populations are not characterized by cohorts of linked mutations (Fig. 2e–h). Instead, the dynamics of each mutation is largely independent of other variation in the population. In these populations, mutations that occur on different backgrounds fix independently, while others briefly hitchhike to moderate frequencies where they persist or are eliminated from the population.
Sex speeds adaptation by altering the dynamics of molecular evolution | Nature

Why does the Desai team have to wait for 90 generations for their yeast to do sexual replication and get improved fitness? What is the definition that Desai uses for fixation and how does it differ from the correct definition?

[amkleinman (Alan Kleinman)]

@beaglelady

That would be ridiculous. He was wrong about some things and had no knowledge of genetics. But he lived a long time ago, and the theory of evolution is constantly being tested, developed, and refined. That’s what makes it a robust scientific theory. On the other hand, pseudo-scientific ideas, like Intelligent Design and astrology, make no progress.

Based on your scientific understanding of biological evolution, explain to us what law of physics is applicable to biological competition.

[amkleinman (Alan Kleinman)]

Hi Steve, welcome to the discussion

@amkleinman

The joint probability of random events occurring is computed using the multiplication rule.

@glipsnort

That’s correct (assuming the events are independent).

It also applies to dependent events (conditional probabilities) but you have to take into account a reduced sample space, mutation B must occur on some member that already has A, not any member of the population.

@amkleinman

That is why it takes a billion replications for each adaptive step in the Kishony and Lenski experiments.

@glipsnort

That’s not correct. The bulk of the time required for each adaptive step is for the most fit current mutant (which may be one of many beneficial mutations in the current population) to become common enough in the population for it to be the likely background for a new beneficial mutation.

You will have to correct Kishony then because he states it takes a billion replications for each adaptive step, and the data from the Lenski experiment shows that it takes a billion replications (of the most fit variant) before there is a high probability of the next adaptive mutation occurring. You should also be aware that biological competition is minimal in the Kishony experiment so none of his variants are fixed in his population.

@amkleinman

It works the same way for eukaryotes.

@glipsnort

As has already been explained to you, that is precisely wrong. In eukaryotes, recombination permits multiple beneficial mutations to occur and succeed in parallel, mixing and matching along the way to produce combinations of beneficial mutations. There is no need for the extended waiting period required for clonal bacteria.

Do you think that the joint probability of two or more adaptive mutations accumulating on a eukaryotic lineage is not computed using the multiplication rule?

@amkleinman

Do you understand how large a population is required for natural selection and adaptation to operate?

@glipsnort

Yes, I do – I’ve done such modeling on multiple occasions. Have you? Please present your model.

Here is the link to the model for descent with modification and adaptation to a single selection pressure:
The basic science and mathematics of random mutation and natural selection
And here is how you do the mathematics for descent with modification and adaptation to multiple simultaneous selection pressures:
The mathematics of random mutation and natural selection for multiple simultaneous selection pressures and the evolution of antimicrobial drug resistance
This mathematics can also be done using a Markov process, here is the paper which shows how to do this math:
The Kishony Mega-Plate Experiment, a Markov Process
The last paper was recently accepted for publication.

@amkleinman

Can you give any experimental evidence of punctuated equilibrium or “rapid adaptation”?

@glipsnort

There’s plenty of evidence, including experimental evidence, for rapid adaptation. (Whether it constitutes punctuated equilibrium or not is too subjective to be settled easily.) A classic study on the different rates of adaptation seen in experiments vs adaptive radiations vs very long-term evolution is “Rates of Evolution: Effects of Time and Temporal Scaling”, Philip Gingerich, Science 222:159-161.

Where is your experimental evidence? That is a 40-year-old paper. The only way that evolution can be speeded up is by increasing the mutation rate such as with HIV but even that evolutionary process is stifled by 3-drug therapy. There are many ways to slow adaptive evolution. A couple of ways are by reducing the carrying capacity of the environment and forcing biological competition and increasing the number of selection pressures acting on a population.

[amkleinman (Alan Kleinman)]

Hello Mi,

@SkovandOfMitaze

I did not read everything, and so I’m not sure what all has been stated. But in addition to genetics we can also look at superimposed geological layers with a fossil record showing basal forms developing more and more divergent traits as speciation takes place. So we don’t see humans before the earliest primates. We don’t see primates before the earliest mammals. We don’t see mammals before the earliest tetrapods. We don’t see tetrapods before the earliest bony lunged fish which we don’t see before the earliest species of fish. The theory of evolution is overwhelmingly sound. Genetics further supports it. It does not detract from it. Geology supports it. It’s like a table with dozens of legs.

Experimental evidence shows that there should be a vast number of transitional forms in the fossil record. Experimentation shows that each adaptive step in descent with modification will take about 1/(mutation rate) replications at a minimum. For a mutation rate of 1E-8, each evolutionary step would give 100,000,000 members in that transition population for each evolutionary step. That doesn’t exist in the fossil record.

[rsewell (RON SEWELL)]

Combination therapies are constantly being reformulated to stay ahead of pathogen evolution. Multi-resistant ringworm, a eukaryotic fungus, has recently been in the news. Bacterial superbugs have been a longstanding challenge which is getting worse. The battle against Malaria is a constantly moving target

Unless eradication is successful, target organisms can be expected to develop resistance to combination drugs and chemicals as a matter of time. This is a observed demonstration of evolutionary adaptation.

[glipsnort (Steve Schaffner)]

@amkleinman

Here is the link to the model for descent with modification and adaptation to a single selection pressure:
The basic science and mathematics of random mutation and natural selection
And here is how you do the mathematics for descent with modification and adaptation to multiple simultaneous selection pressures:
The mathematics of random mutation and natural selection for multiple simultaneous selection pressures and the evolution of antimicrobial drug resistance
This mathematics can also be done using a Markov process, here is the paper which shows how to do this math:
The Kishony Mega-Plate Experiment, a Markov Process
The last paper was recently accepted for publication.

Ah, I see who you are.

Joe Felsenstein – who is a genuine expert in this subject – tried to get Alan to come up with a mathematical model for actual evolutionary processes in a very long thread [here].(Evaluating Alan Kleinman's arguments). I suggest anyone thinking of responding in this thread go and read that one. I see no point whatever in engaging in a no doubt equally futile exchange here.

[beaglelady]

@amkleinman

Based on your scientific understanding of biological evolution, explain to us what law of physics is applicable to biological competition.

what is that supposed to mean? You don’t like my comment?

[SkovandOfMitaze (Mi)]

So consider this.

Most likely you are just misunderstanding the science and so you are regurgitating stuff that just carries little scientific value.

A reason to consider why you are wrong is because this theory has been around for a while in the modern era. There are around 8 million scientists worldwide and it seems that the overwhelming majority of them all support evolution. I’ve never seen a figures citing 20,000 scientists rejecting the basic theory of evolution. So that’s about 1/4 of 1% , or 0.25% rejecting it. Even if we had a margin of error of 4x that, it’s just 1%.

Which geneticists are you citing that says evolution is not possible. Like who is the top ten geneticists you are getting this information from?

[amkleinman (Alan Kleinman)]

@T_aquaticus

The multiplication rule does not apply in sexual populations. A mother with beneficial mutation A can mate with a father with beneficial mutation B, and some of their offspring will have both beneficial mutations.

Two questions for you.

1. What is the probability of one parent with mutation A and another parent with mutation B mating to give an offspring with both mutations A and B?
2. What if all adaptive mutationss must occur in a single allele? For example, let’s say you have a drug that you would use to treat malaria but 5 adaptive mutations to that allele give resistance to that drug. How would recombination give all 5 of those mutations in an allele to pass to that offspring?

[amkleinman (Alan Kleinman)]

Why do you think the target is moving?

[amkleinman (Alan Kleinman)]

Is that the same Joe Felsenstein that won’t explain the mathematics of the Lenski experiment or give the mathematics of biological evolution or drug resistance? Did you watch his video where he tries to explain the thermodynamics of biological evolution? You can see that video here:
Fisher Memorial lecture 2018 by Joe Felsenstein
He doesn’t do his thermodynamics correctly. Perhaps Joe Felsenstein will be famous for his failure to explain how drug resistance evolves despite all his mathematical knowledge of biological evolution.
Based on your scientific understanding of the physics of biological evolution from the Felsenstein video, explain to us what law of physics is applicable to biological competition.

[amkleinman (Alan Kleinman)]

Don’t you know that the first law of thermodynamics affects how biological competition works?