Genetic Engineering and Genetic Alteration of humans

[FrumiousBandersnatch]

I think you will find that I wasn’t talking about the increase in mutation rate but an increase in the accumulation of mutations.

Good, well that's just a normal evolutionary process - when the environment changes so that certain kinds of mutations are no longer deleterious, they will tend to accumulate in the population through genetic drift.

Not all mutations are weeded out as a result of improved medical interventions.

What makes you think any are weeded out that way? medical interventions make them more likely to persist.

That was the point of the paper I linked that not all disease disorders are completely cured or eradicated and modern medicine allows more sick and disordered people to live to allow more harmful mutations to hang around. The mutations are too small for natural selection to weed out.

My point was that, evolutionarily speaking, these mutations are no longer significantly deleterious (they're 'too small' as you put it). That's why they can persist. Mutations are deleterious when they significantly reduce reproductive success, and that can change as the environment changes. Our medical interventions are a change in our evolutionary environment that has made a number of mutations no longer deleterious.

... modern ways of life invite diseases and disorders too fast for selection to weed out.

Your writing is vague and ambiguous - are you talking about selection weeding out diseases and disorders or weeding out mutations? Most diseases and disorders are not the direct result of deleterious mutations.

If you mean mutations, which diseases and disorders are a result of 'modern ways of life' causing mutations too fast for selection to weed out?

This is supported by the fact that disorders are increasing

In the United States, the incidences of a variety of afflictions including autism, male infertility, asthma, immune-system disorders, diabetes, etc., already exhibit increases exceeding the expected rate.

You need to distinguish between the number of disorders increasing and the incidence extant disorders increasing. The text you quote (I assume it's a quote, there's no link for it) is about the incidence of particular disorders, not the number of disorders.

The increase in incidence of those disorders is probably not due to mutations accumulating - they are associated with lifestyle changes that have happened far too rapidly for that (e.g. China, Japan).

In general, the impact (both the number and incidence) of disorders and diseases has fallen dramatically over the last 200 years (we have even completely eradicated smallpox), and average life expectancy has doubled. This would not be expected if what you claim is true.

What we are mainly seeing is an increase in the incidence of certain disorders and an increase in the diagnostic efficacy of others. Much of this is due to them becoming more noticeable as the background of severe infectious disease has dropped.

My point is not just about genetic disorders in humans, but generally, human activity is causing more infections, diseases, and disorders in humans some of which are related to being genetically modified.

Which disorders are related to what being genetically modified?

Now a recent study published in the Annals of Internal Medicine suggests far more people than previously thought are carrying variants of rare genetic diseases and could force us to redefine what is considered a healthy genome.

Far More People Than Thought Are Carrying Rare Genetic Diseases - ExtremeTech
Estimating Mutation Load in Human Genomes
Millions of new variants have been discovered in human genomic datasets. Many of these, especially rare variants, have been annotated as deleterious
Moreover a large number of deleterious mutations may also exist in the non-coding portion of the genome75, meaning that studies focusing on exomes have only studied a small portion of the mutational load that may exist in the human genome37.
Estimating Mutation Load in Human Genomes

Those estimates concern newly discovered mutations and incidences that have accumulated in the Homo sap. genome over evolutionary timescales. As genetic sequencing and analysis technologies improve, so the original rough estimates are being revised.

That is what some of the papers are saying that the mutations are only slight and not picked up by selection. But they accumulate over time and this can have a harmful effect as the more get into the gene pool.

That's a speculative claim. Mutations have always accumulated over time; those that are significantly deleterious are removed over the long term. Of course, if the environment changes, e.g. we lose our medical and social health resources, those mutations may become disadvantageous. But this is just how evolution works - if you can suggest a way to reduce the number of slightly deleterious mutations that occur, you'll be up for a Nobel prize.

What I am talking about are human-induced diseases and disorders that come from lifestyle and there are many examples.

The most obvious are heart disease, diabetes and obesity
The number of American children with chronic illnesses has roughly quadrupled in the past 50 years, including an almost fourfold increase in childhood obesity in the past three decades and twice the asthma rates since the 1980s. People are more sedentary and less physically active than before, and fast food is more available. type I diabetes, "a childhood form of diabetes almost unheard of at the turn of the 20th century, is up from one in 5,000 or 10,000 to one in 250 in some regions
Why Are Humans Always So Sick? | Live Science

There are many more Multiple sclerosis, metabolic syndrome, malfunctions of the immune system, etc.
Chronic and degenerative illnesses are largely new to mankind. In fact, diseases such as cancer, diabetes, fibromyalgia, and multiple sclerosis have been termed modern or man-made diseases because they were relatively rare until three hundred years or so ago.
Modern Disease and the Rise of the Allopathic Model | Chelsea Green Publishing

But it is also the many chronic diseases that the above diseases bring as well like cancers, liver, lung kidney-pancreas diseases, disorders associated with metabolic syndrome which can be many such as atherosclerosis and musculoskeletal diseases. Too many to name but all mostly associated with lifestyle.

Sure, many result from 'self-imposed' lifestyle choices, but many are consequence of the increase in life expectancy and a reduction in birth rate, leading to an increase in the elderly population, who are more likely to suffer the diseases of old age, such as cancer, heart disease, and so-on.

Why if the phenotypes of all living things are a representation of our genotypes and this is closely connected to the environment and what happens to it then this is going to have an effect on our bodies and minds and thus our genetic state sooner or later. As mentioned this is especially true with epigenetics. So if our environments are polluted or there are many pathogens or we are living under stress because of modern life or we destroy other species and ecosystems which deplete the overall variety of life and the health of biodiversity this will affect our genetic expression and makeup and this can be passed to future generations.

So I have mentioned this above with epigenetics and here is some evidence.

Epigenetics and Human Disease
Genetic causes for human disorders are being discovered at an unprecedented pace. A growing subclass of disease-causing mutations involves changes in the epigenome or in the abundance and activity of proteins that regulate chromatin structure. This article focuses on research that has uncovered human diseases that stem from such epigenetic deregulation.

The Barker or thrifty phenotype hypothesis, which has evolved into the fetal origins hypothesis of adult disease posits that reduced fetal nutrition is associated with an increased risk of adult disorders including coronary heart disease, stroke, diabetes, and hypertension (Guilloteau et al. 2009; Calkins and Devaskar 2011; Dyer and Rosenfeld 2011).
Epigenetics and Human Disease

Epigenetic influences and human diseases
The findings from various studies clearly suggest that aberrations in the epigenome are critical factors in the initiation and progression of many diseases.
Epigenetics of human diseases and scope in future therapeutics - ScienceDirect

Epigenetic Inheritance of Disease and Disease Risk
Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations.
Epigenetic Inheritance of Disease and Disease Risk

Again, these papers are about new discoveries in the genome and epigenome not new changes to the genome and epigenome. We're discovering unexpected things about them that we didn't know before. That's how science works.

Your vague handwaving about damage to the environment affecting our genetic state 'sooner or later' is just that, vague handwaving. Of course, our genetics will respond to changes in the environment, that's the essence of evolution; and of course, if we pollute the environment with mutagens, we'll probably cause undesirable mutations, so we should try not to do that.

 

[Larniavc]

That's when it gets tricky. Sure, everyone wants diseases cured, and only fundamentalists insist that diseases are God's will, but most of us feel uncomfortable when it comes to enhancing or changing what makes a human, human. Or, what does make a human, human? And does it even matter? That's the question.

I for one would jump at the chance to have biological enhancements. That would be ace.

 

[Ophiolite]

My point was that, evolutionarily speaking, these mutations are no longer significantly deleterious (they're 'too small' as you put it). That's why they can persist. Mutations are deleterious when they significantly reduce reproductive success, and that can change as the environment changes. Our medical interventions are a change in our evolutionary environment that has made a number of mutations no longer deleterious.

This is the point that seems to go over some people heads, no matter how often one explains it. I suspect it stems from the fact that many people still misunderstand the meaning of fittest in the phrase survival of the fittest.

It is misunderstood by them as fit in the sense that we get fit in the gym, or by cycling fifteen miles a day. They do not understand it means biologically well suited to ones existing environment.

 

[FrumiousBandersnatch]

This is the point that seems to go over some people heads, no matter how often one explains it. I suspect it stems from the fact that many people still misunderstand the meaning of fittest in the phrase survival of the fittest.

It is misunderstood by them as fit in the sense that we get fit in the gym, or by cycling fifteen miles a day. They do not understand it means biologically well suited to ones existing environment.

Yes, I think that's often the case - but I think in this particular case, the misunderstanding is the idea that mutations are intrinsically either beneficial, neutral, or deleterious, rather than being so depending on the environment and its selection pressures (where the environment can include the internal milieu of the body itself).

There is also the distinction between evolutionary fitness and having an illness or condition that doesn't significantly affect reproductive success.

When these elements are confused, conflated, or equivocated, no coherent debate is possible.

 

[stevevw]

Good, well that's just a normal evolutionary process - when the environment changes so that certain kinds of mutations are no longer deleterious, they will tend to accumulate in the population through genetic drift.

But papers are saying that deleterious mutations have accumulated and become fixed despite environmental changes and they negatively affect fitness.
It has been suggested that humans may suffer a high genomic deleterious mutation rate1,2. A large number of slightly deleterious mutations may, therefore, have become fixed in hominid lineages.
High genomic deleterious mutation rates in hominids

Millions of new variants have been discovered in human genomic datasets. Many of these, especially rare variants, have been annotated as deleterious.
Moreover, a large number of deleterious mutations may also exist in the non-coding portion of the genome75, meaning that studies focusing on exomes have only studied a small portion of the mutational load that may exist in the human genome37.
Estimating Mutation Load in Human Genomes

What makes you think any are weeded out that way? medical interventions make them more likely to persist.

You said earlier that changing environments, in this case, improved medical interventions minimize deleterious mutations because the diseases have been eradicated. I am saying that not all of the diseases have been eradicated by improved medicines. Often they allow sick and disordered people to survive while still carrying deleterious mutations. This allows more deleterious mutations to stay in the gene pool.

My point was that, evolutionarily speaking, these mutations are no longer significantly deleterious (they're 'too small' as you put it). That's why they can persist. Mutations are deleterious when they significantly reduce reproductive success, and that can change as the environment changes. Our medical interventions are a change in our evolutionary environment that has made a number of mutations no longer deleterious.

Then why do the papers say that very slightly deleterious mutations have been accumulating in humans?
Furthermore, the level of selective constraint in hominid protein-coding sequences is atypically (unusually) low. A large number of slightly deleterious mutations may, therefore, have become fixed in hominid lineages.
http://www.nature.com/nature/j.....344a0.html

Many multicellular eukaryotes have reasonably high per-generation mutation rates. Consequently, most populations harbor an abundance of segregating deleterious alleles. These alleles, most of which are of small effect individually, collectively can reduce substantially the fitness of individuals relative to what it would be otherwise; this is mutation load.
http://www.annualreviews.org/doi/abs/10.1146/annurev-ecolsys-110411-160257

Now consider the effect of diminished selection on mutations with small enough effects to be impervious to detection by genetic screening but subject to amelioration by medical intervention (e.g., the removal of visual acuity issues by optometry). Ordinarily, a heritable mutation causing a 1% reduction in fitness will be eliminated from a population in ∼100 generations, but the mitigation of fitness effects will extend the life span of preexisting deleterious mutations, and without a comparable reduction in the mutation rate, the equilibrium frequencies of deleterious alleles will increase.
Mutation and Human Exceptionalism: Our Future Genetic Load

You need to distinguish between the number of disorders increasing and the incidence of extant disorders increasing. The text you quote (I assume it's a quote, there's no link for it) is about the incidence of particular disorders, not the number of disorders.

The increase in incidence of those disorders is probably not due to mutations accumulating - they are associated with lifestyle changes that have happened far too rapidly for that (e.g. China, Japan).

In general, the impact (both the number and incidence) of disorders and diseases has fallen dramatically over the last 200 years (we have even completely eradicated smallpox), and average life expectancy has doubled. This would not be expected if what you claim is true.

What we are mainly seeing is an increase in the incidence of certain disorders and an increase in the diagnostic efficacy of others. Much of this is due to them becoming more noticeable as the background of severe infectious disease has dropped.

The context for that quote which I have included below with the original section quoted was about how natural selection is relaxed due to modern advances such as medical interventions. Though they may have made improvements they also relaxed natural selection by allowing individuals to survive while still carrying the effects of cancers and heart disease for example which allows the associated harmful mutations to linger in the population. So the altered environments due to advances in medical tech are doing the opposite of what you say by increasing certain diseases and disorders.

it remains difficult to escape the conclusion that numerous physical and psychological attributes are likely to slowly deteriorate in technologically advanced societies. In the United States, the incidences of a variety of afflictions including autism, male infertility, asthma, immune-system disorders, diabetes, etc., already exhibit increases exceeding the expected rate. Much of this change is almost certainly due to alterations in environmental factors. However, mitigating these effects by modifications in behavior and/or medical intervention will also simply exacerbate the issues noted above by relaxing selection on any underlying genetic factors.
Mutation and Human Exceptionalism: Our Future Genetic Load[/QUOTE]

 

[stevevw]

That's a speculative claim. Mutations have always accumulated over time; those that are significantly deleterious are removed over the long term.

As noted in the previous post it seems that slightly deleterious can hang around and cause a fitness loss
Many multicellular eukaryotes have reasonably high per-generation mutation rates. Consequently, most populations harbor an abundance of segregating deleterious alleles. These alleles, most of which are of small effect individually, collectively can reduce substantially the fitness of individuals relative to what it would be otherwise; this is mutation load.
https://www.annualreviews.org/doi/full/10.1146/annurev-ecolsys-110411-160257

Moreover a large number of deleterious mutations may also exist in the non-coding portion of the genome75, meaning that studies focusing on exomes have only studied a small portion of the mutational load that may exist in the human genome37.
Estimating Mutation Load in Human Genomes

mutations are not large enough to be seen and thus accumulate leading to a cost to fitness. Of course, if the environment changes, e.g. we lose our medical and social health resources, those mutations may become disadvantageous.

Yet these papers are saying that it is because of the improved medical interventions that are relaxing selection and causing more harmful mutations to accumulate because more people with diseases are being kept alive.

But this is just how evolution works - if you can suggest a way to reduce the number of slightly deleterious mutations that occur, you'll be up for a Nobel prize.

I think that is the point of the article with these slightly deleterious mutations in that they are too small and are associated with different parts of the genome that they cannot be weeded out.

To some extent, mutation load is not a treatable problem because it is so diffuse (i.e., many thousands of rare deleterious alleles of small effect affecting fitness in a variety of ways).
https://www.annualreviews.org/doi/full/10.1146/annurev-ecolsys-110411-160257

Sure, many result from 'self-imposed' lifestyle choices, but many are consequence of the increase in life expectancy and a reduction in birth rate, leading to an increase in the elderly population, who are more likely to suffer the diseases of old age, such as cancer, heart disease, and so-on.

many of the diseases like obesity and diabetes but also heart disease are happening in children and younger to middle-aged adults. Especially mental disorders that happen more in young people.

Again, these papers are about new discoveries in the genome and epigenome not new changes to the genome and epigenome. We're discovering unexpected things about them that we didn't know before. That's how science works.

The point is we are discovering new ways in which lifestyle such as pollutants, pathogens, stress, diet can contribute to altering our genetic makeup and being passed onto future generations which are directly linked to lifestyle choices.

Your vague handwaving about damage to the environment affecting our genetic state 'sooner or later' is just that, vague handwaving. Of course, our genetics will respond to changes in the environment, that's the essence of evolution; and of course, if we pollute the environment with mutagens, we'll probably cause undesirable mutations, so we should try not to do that.

I am confused, you just called it vague hand waving and then agreed with me that it is a problem.

 

[Ophiolite]

Yet these papers are saying that it is because of the improved medical interventions that are relaxing selection and causing more harmful mutations to accumulate because more people with diseases are being kept alive.

The mutations are not harmful in an environment in which they can be dealt with by medical interventions.
Why are you finding that difficult to understand?

 

[FrumiousBandersnatch]

But papers are saying that deleterious mutations have accumulated and become fixed despite environmental changes and they negatively affect fitness.
It has been suggested that humans may suffer a high genomic deleterious mutation rate1,2. A large number of slightly deleterious mutations may, therefore, have become fixed in hominid lineages.
High genomic deleterious mutation rates in hominids

Millions of new variants have been discovered in human genomic datasets. Many of these, especially rare variants, have been annotated as deleterious.
Moreover, a large number of deleterious mutations may also exist in the non-coding portion of the genome75, meaning that studies focusing on exomes have only studied a small portion of the mutational load that may exist in the human genome37.
Estimating Mutation Load in Human Genomes

I should have said, "... no longer significantly deleterious..."

But those papers haven't clearly defined their terms, so it's hard to make specific comment. It's debatable whether an overall drop in the reproductive success of a population is necessarily deleterious, and even more debatable whether that can be described as a reduction in fitness. Evolutionary fitness concerns individual reproductive success in terms of contribution to the gene pool of the next generation.

You said earlier that changing environments, in this case, improved medical interventions minimize deleterious mutations because the diseases have been eradicated.

I didn't say that. If you want to quote me, do so.

Then why do the papers say that very slightly deleterious mutations have been accumulating in humans?

I suspect they mean deleterious in the medical sense, e.g. increasing an individual’s susceptibility or predisposition to a certain disease or disorder. Over the long term, if extinction doesn't occur, an equilibrium will be reached where the population supports a certain level of deleterious mutations.

The context for that quote which I have included below with the original section quoted was about how natural selection is relaxed due to modern advances such as medical interventions. Though they may have made improvements they also relaxed natural selection by allowing individuals to survive while still carrying the effects of cancers and heart disease for example which allows the associated harmful mutations to linger in the population. So the altered environments due to advances in medical tech are doing the opposite of what you say by increasing certain diseases and disorders.

What I said was, "What we are mainly seeing is an increase in the incidence of certain disorders and an increase in the diagnostic efficacy of others."

An increase in certain diseases and disorders doesn't mean an overall increase in diseases and disorders.

 

[FrumiousBandersnatch]

As noted in the previous post it seems that slightly deleterious can hang around and cause a fitness loss
Many multicellular eukaryotes have reasonably high per-generation mutation rates. Consequently, most populations harbor an abundance of segregating deleterious alleles. These alleles, most of which are of small effect individually, collectively can reduce substantially the fitness of individuals relative to what it would be otherwise; this is mutation load.
https://www.annualreviews.org/doi/full/10.1146/annurev-ecolsys-110411-160257

I don't really know what that paper is trying to say - it looks like either sloppy writing or sloppy thinking. As I mentioned in the previous post, fitness is a measure of individual contribution to the next generation of the population.

If the slightly deleterious mutations are established in the population, it doesn't make sense to suggest that individuals are relatively less fit than they would otherwise have been. They may have fewer offspring than they would otherwise have had, but that will apply to the population as a whole, so their relative fitness will be the same.

... I think that is the point of the article with these slightly deleterious mutations in that they are too small and are associated with different parts of the genome that they cannot be weeded out.

It doesn't matter where they are in the genome, selection (weeding out) is done by phenotype, not genotype.

many of the diseases like obesity and diabetes but also heart disease are happening in children and younger to middle-aged adults. Especially mental disorders that happen more in young people.

The point is we are discovering new ways in which lifestyle such as pollutants, pathogens, stress, diet can contribute to altering our genetic makeup and being passed onto future generations which are directly linked to lifestyle choices.

You have yet to show any evidence that our modern lifestyle choices are causing mutations that are responsible for the increase in 'lifestyle' disorders and diseases.

I am confused, you just called it vague hand waving and then agreed with me that it is a problem.

You waffled about our environment 'sooner or later' affecting our genome as if it was a novel insight - I was just pointing out that it's not.

 

[stevevw]

The mutations are not harmful in an environment in which they can be dealt with by medical interventions.
Why are you finding that difficult to understand?

Then why has the paper stated that despite medical interventions or rather because of them especially in industrialized and technically/medically advanced societies that this has relaxed natural selection and caused slightly deleterious mutations to remain in the gene pool and accumulate?

What is exceptional about humans is the recent detachment from the challenges of the natural environment and the ability to modify phenotypic traits in ways that mitigate the fitness effects of mutations, e.g., precision and personalized medicine. This results in a relaxation of selection against mildly deleterious mutations, including those magnifying the mutation rate itself. The long-term consequence of such effects is an expected genetic deterioration in the baseline human condition, potentially measurable on the timescale of a few generations in westernized societies, and because the brain is a particularly large mutational target, this is of particular concern.

it remains difficult to escape the conclusion that numerous physical and psychological attributes are likely to slowly deteriorate in technologically advanced societies. In the United States, the incidences of a variety of afflictions including autism, male infertility, asthma, immune-system disorders, diabetes, etc., already exhibit increases exceeding the expected rate. Much of this change is almost certainly due to alterations in environmental factors. However, mitigating these effects by modifications in behavior and/or medical intervention will also simply exacerbate the issues noted above by relaxing selection on any underlying genetic factors.

This means that the myriad of clinical procedures for mitigating the consequences of bad genes (e.g., surgical procedures, pharmaceuticals, nutritional supplements, and physical and psychiatric therapies) can only result in the relaxation of natural selection against a broad class of deleterious mutations.

Unless some altered course is taken, as improved biomedical procedures continue to minimize the cumulative consequences of our genetic (and/or environmentally induced) afflictions and the associated biomedical industries reap the financial rewards, this will come at a progressively increasing cost for individuals.
Mutation and Human Exceptionalism: Our Future Genetic Load

 

[Ophiolite]

Then why has the paper stated that despite medical interventions or rather because of them especially in industrialized and technically/medically advanced societies that this has relaxed natural selection and caused slightly deleterious mutations to remain in the gene pool and accumulate?

1. They are using a singular and restricted sense of the term "natural selection".
2. They are, seemingly, expressing concern based upon the load this places upon medical resources and the risks that these this creates should those medical resources cease to be available. i.e. what happens if the environment reverts to prior state where the conditions prohibited or reduced successful reproduction.
3. They appear to be, quite appropriately, concerned about the impact the mutations and their resultant conditions may have on the individuals life. However, if the individual has successfully reproduced any discomfort, pain, illness or death they subsequently suffer is irrelevant to evolution.

 

[stevevw]

1. They are using a singular and restricted sense of the term "natural selection".
2. They are, seemingly, expressing concern based upon the load this places upon medical resources and the risks that these this creates should those medical resources cease to be available. i.e. what happens if the environment reverts to prior state where the conditions prohibited or reduced successful reproduction.
3. They appear to be, quite appropriately, concerned about the impact the mutations and their resultant conditions may have on the individuals life. However, if the individual has successfully reproduced any discomfort, pain, illness or death they subsequently suffer is irrelevant to evolution.

I think you are overlooking the most relevant point relating to what I was saying IE

detachment from the challenges of the natural environment and the ability to modify phenotypic traits in ways that mitigate the fitness effects of mutations, e.g., precision and personalized medicine. This results in a relaxation of selection against mildly deleterious mutations including those magnifying the mutation rate itself. The long-term consequence of such effects is an expected genetic deterioration in the baseline human condition

That humans through medical advances have created an artificial environment that doesn't allow evolution to follow its natural course. Medical advances allow sick and disordered people to stay alive and this is minimizing the power of natural selection and its ability to deal with the mildly deleterious mutations that are causing these ailments. This is compounded by modern life which creates more pathogens and mutagens that also affect humans genetically. This as a number of papers are now saying is causing and leading to a deterioration in the baseline human conditions. In other words, increasing diseases and disorders that we are now seeing more and more are having an effect on humans.

 

[stevevw]

I should have said, "... no longer significantly deleterious..."

But those papers haven't clearly defined their terms, so it's hard to make specific comment. It's debatable whether an overall drop in the reproductive success of a population is necessarily deleterious, and even more debatable whether that can be described as a reduction in fitness. Evolutionary fitness concerns individual reproductive success in terms of contribution to the gene pool of the next generation.

Well all I can go off is what these papers are saying. Not just one but several and usually that is a good indication of something more than likely being correct.

I didn't say that. If you want to quote me, do so.

Then maybe I have misunderstood what you said here

FrumiousBandersnatch said #41 Our medical interventions are a change in our evolutionary environment that has made a number of mutations no longer deleterious.

I suspect they mean deleterious in the medical sense, e.g. increasing an individual’s susceptibility or predisposition to a certain disease or disorder. Over the long term, if extinction doesn't occur, an equilibrium will be reached where the population supports a certain level of deleterious mutations.

I thought they meant that because medical interventions are keeping people alive with disease and disorders that this is also keeping the diseases and disorders in the gene pool. Selections ability is weakened because it cannot weed out these problems because humans are countering any effect be selection. Also, modern life technology and industry are working too fast for selection to have time to weed out all the new pathogens and mutagens being introduced.

What I said was, "What we are mainly seeing is an increase in the incidence of certain disorders and an increase in the diagnostic efficacy of others."

An increase in certain diseases and disorders doesn't mean an overall increase in diseases and disorders.

As far as I understand it the increase in diseases and disorders is not just for certain ones but a wide range. Yes, we are improving our diagnostic techniques, but the papers are implying that there is an increase in diseases and disorders that will be detrimental to humans in the near future. So that points to an increase or overload happening that needs additional diseases and disorders either de novo or increases in current ones.

 

[stevevw]

I don't really know what that paper is trying to say - it looks like either sloppy writing or sloppy thinking. As I mentioned in the previous post, fitness is a measure of individual contribution to the next generation of the population.

If the slightly deleterious mutations are established in the population, it doesn't make sense to suggest that individuals are relatively less fit than they would otherwise have been. They may have fewer offspring than they would otherwise have had, but that will apply to the population as a whole, so their relative fitness will be the same.

I guess they're talking about a slow death in that these mutational effects are not so obvious to natural selection overall but may gradually make individuals relatively sick but still able to reproduce. Therefore, these mutations can spread and accumulate and make humans sicker overall but not to the point where they cannot reproduce and still survive.

It doesn't matter where they are in the genome, selection (weeding out) is done by phenotype, not genotype.

Yes, but the changes to human phenotypes is not great enough that it is obvious for the natural process of selection to weed them out at least for now. So, they remain and spread and gradually this will have an effect on the genotype as more harmful mutations associated with the diseases and disorders get into the gene pool.

You have yet to show any evidence that our modern lifestyle choices are causing mutations that are responsible for the increase in 'lifestyle' disorders and diseases.

I thought I just did. Epigenetics affects are being found to be a contributor to changes in the genes or the expression of genes of humans which can be passed down. The main contribution of epigenetic changes is lifestyle such as stress, diet, pollutants, pathogens and mutagens being introduced.

Climate Change Is Already Altering the World’s Gene Pool
the planet’s warming has interfered with more than 80 percent of biological processes, including genetics, body mass, sex ratios, and productivity.
“Reduced genetic diversity in crops, inconsistent crop yields, decreased productivity in fisheries from reduced body size, and decreased fruit yields from fewer winter chill events threaten food security,”
Changes in disease distribution and the emergence of new pathogens and pests are a “direct threat to human health.” Mosquitoes are more efficient at spreading diseases such as chikungunya, dengue, and possibly Zika. Warmer weather is also altering the genes of many species.
Climate Change Is Already Altering the World’s Gene Pool

The Impact of Traditional Food and Lifestyle Behavior on Epigenetic Burden of Chronic Disease
The world is experiencing an ever-increasing burden of Noncommunicable chronic diseases (NCCDs), which have been traditionally associated with adoption of unhealthy western lifestyle factors including the consumption of energy-dense and highly processed foods, physical inactivity, tobacco and alcohol use, exposure to environmental chemicals among others. There is increasing evidence that such environmental factors could induce epigenetic alterations that are transmitted across several generations to program the risk of adult NCCDs in those prenatally exposed. It was argued in this paper that the experiences of our ancestors likely starting around the time of the industrial revolution and those of our immediate parents may have cumulatively programmed us to have increased risks of NCCDs, thus the current huge burden and projected increases in the near future.
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Epigenetics and Human Disease
Genetic causes for human disorders are being discovered at an unprecedented pace. A growing subclass of disease-causing mutations involve changes in the epigenome or in the abundance and activity of proteins that regulate chromatin structure. This article focuses on research that has uncovered human diseases that stem from such epigenetic deregulation.

The Barker or thrifty phenotype hypothesis, which has evolved into the fetal origins hypothesis of adult disease posits that reduced fetal nutrition is associated with an increased risk of adult disorders including coronary heart disease, stroke, diabetes, and hypertension (Guilloteau et al. 2009; Calkins and Devaskar 2011; Dyer and Rosenfeld 2011).

Data from human studies, as well as animal models, are providing evidence that the environment can affect epigenetic marks and, as a result, gene function.
Epigenetics and Human Disease

Epigenetic influences and human diseases
The findings from various studies clearly suggest that aberrations in the epigenome are critical factors in the initiation and progression of many diseases.
Epigenetics of human diseases and scope in future therapeutics - ScienceDirect

Epigenetic Inheritance of Disease and Disease Risk
Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations.
Epigenetic Inheritance of Disease and Disease Risk

 

[FrumiousBandersnatch]

Well all I can go off is what these papers are saying. Not just one but several and usually that is a good indication of something more than likely being correct.

The question isn't whether they're correct, but whether you're interpreting them correctly. The advantage of going straight to the published research is that you can skip the media hype and attention-seeking. The disadvantage is that that they're specialised technical material and you need to be sure you're interpreting what they say correctly. This means that it helps to be familiar with the language (e.g. jargon) they're using and the subject matter; if they haven't clearly defined their terms and what they're saying sounds a bit strange, one should suspect a misinterpretation.

Then maybe I have misunderstood what you said here

FrumiousBandersnatch said #41 Our medical interventions are a change in our evolutionary environment that has made a number of mutations no longer deleterious.

Making 'a number' of mutations no longer deleterious is not the same as "minimizing deleterious mutations". Note that I also said nothing about the reduction being, "because the diseases have been eradicated" - you made that up.

I thought they meant that because medical interventions are keeping people alive with disease and disorders that this is also keeping the diseases and disorders in the gene pool.

Very few diseases and disorders are 'in the gene pool'. In general, there is a genetic susceptibility to various diseases & disorders.

Selections ability is weakened because it cannot weed out these problems because humans are countering any effect be selection. Also, modern life technology and industry are working too fast for selection to have time to weed out all the new pathogens and mutagens being introduced.

As I said before, if selection is no longer acting on them, then in evolutionary terms they are no longer problems, although the individuals concerned might prefer not to have them.

You make it sound like the pace of "modern life technology and industry" preventing selection weeding out the mutations which, thanks to modern life, technology, and industry, are no longer a fatal problem, is a bad thing; but it's a good thing - if you think saving lives and enabling people to have families is good. 'Weeding out' mutations by selection, in the short term, means death.

Why do you suppose technology and industry are working so fast to develop Covid19 treatments and vaccines? Hint: it's to slow down the activity of selection on the population; IOW to save lives.

And the idea that selection can weed out 'new pathogens and mutagens' is incoherent - what did you mean?

As far as I understand it the increase in diseases and disorders is not just for certain ones but a wide range.

My bad, I meant certain types of diseases and disorders, but that misses my point - An increase in certain types of diseases and disorders doesn't mean an overall increase in diseases and disorders.

 

[FrumiousBandersnatch]

I guess they're talking about a slow death in that these mutational effects are not so obvious to natural selection overall but may gradually make individuals relatively sick but still able to reproduce.

More likely an increased probability of succumbing to the disorder or disease in question.

Therefore, these mutations can spread and accumulate and make humans sicker overall but not to the point where they cannot reproduce and still survive.

That's what I said - an equilibrium is reached. This is simply how evolutions works. Modern technology and medicine has simply moved the equilibrium point slightly to our short-term advantage. On the other hand, the resulting damage to the environment will probably more than redress the balance in lives lost in the long term if things don't change significantly...

Yes, but the changes to human phenotypes is not great enough that it is obvious for the natural process of selection to weed them out at least for now.

If the change to the phenotype is not sufficient for selection to act on them, then they're not evolutionarily significant changes, by definition.

I thought I just did. Epigenetics affects are being found to be a contributor to changes in the genes or the expression of genes of humans which can be passed down. The main contribution of epigenetic changes is lifestyle such as stress, diet, pollutants, pathogens and mutagens being introduced.

Climate Change Is Already Altering the World’s Gene Pool
the planet’s warming has interfered with more than 80 percent of biological processes, including genetics, body mass, sex ratios, and productivity.
“Reduced genetic diversity in crops, inconsistent crop yields, decreased productivity in fisheries from reduced body size, and decreased fruit yields from fewer winter chill events threaten food security,”
Changes in disease distribution and the emergence of new pathogens and pests are a “direct threat to human health.” Mosquitoes are more efficient at spreading diseases such as chikungunya, dengue, and possibly Zika. Warmer weather is also altering the genes of many species.
Climate Change Is Already Altering the World’s Gene Pool

The Impact of Traditional Food and Lifestyle Behavior on Epigenetic Burden of Chronic Disease
The world is experiencing an ever-increasing burden of Noncommunicable chronic diseases (NCCDs), which have been traditionally associated with adoption of unhealthy western lifestyle factors including the consumption of energy-dense and highly processed foods, physical inactivity, tobacco and alcohol use, exposure to environmental chemicals among others. There is increasing evidence that such environmental factors could induce epigenetic alterations that are transmitted across several generations to program the risk of adult NCCDs in those prenatally exposed. It was argued in this paper that the experiences of our ancestors likely starting around the time of the industrial revolution and those of our immediate parents may have cumulatively programmed us to have increased risks of NCCDs, thus the current huge burden and projected increases in the near future.
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Epigenetics and Human Disease
Genetic causes for human disorders are being discovered at an unprecedented pace. A growing subclass of disease-causing mutations involve changes in the epigenome or in the abundance and activity of proteins that regulate chromatin structure. This article focuses on research that has uncovered human diseases that stem from such epigenetic deregulation.

The Barker or thrifty phenotype hypothesis, which has evolved into the fetal origins hypothesis of adult disease posits that reduced fetal nutrition is associated with an increased risk of adult disorders including coronary heart disease, stroke, diabetes, and hypertension (Guilloteau et al. 2009; Calkins and Devaskar 2011; Dyer and Rosenfeld 2011).

Data from human studies, as well as animal models, are providing evidence that the environment can affect epigenetic marks and, as a result, gene function.
Epigenetics and Human Disease

Epigenetic influences and human diseases
The findings from various studies clearly suggest that aberrations in the epigenome are critical factors in the initiation and progression of many diseases.
Epigenetics of human diseases and scope in future therapeutics - ScienceDirect

Epigenetic Inheritance of Disease and Disease Risk
Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations.
Epigenetic Inheritance of Disease and Disease Risk

Epigenetic changes are not mutations.

You have yet to show any evidence that our modern lifestyle choices are causing mutations that are responsible for the increase in 'lifestyle' disorders and diseases.

 

[stevevw]

The question isn't whether they're correct, but whether you're interpreting them correctly. The advantage of going straight to the published research is that you can skip the media hype and attention-seeking. The disadvantage is that that they're specialised technical material and you need to be sure you're interpreting what they say correctly. This means that it helps to be familiar with the language (e.g. jargon) they're using and the subject matter; if they haven't clearly defined their terms and what they're saying sounds a bit strange, one should suspect a misinterpretation.

I am not a biologist or a geneticist but have studied these areas for years and done some units covering this at University. I also have commentary from other experts to go by and they are clear about what the papers are saying. Yes, some sensationalize things, but you can still get the basic gist of what is being said. That seems to be that modern life has brought about more situations that subject humans to genetic changes and relaxation of natural selection that can potentially cause problems for humans.

Logic also tells us that humans carry a lot of diseases and disorders. The point is most diseases and disorders have an agenetic base and therefore this signifies genetic damage. This is not diminishing and if anything seems to be increasing. Whether this is because of an actual increase or existing diseases and disorders being identified I would say both. But there is definitely an increase in mental illness and intellectual disabilities.

Very few diseases and disorders are 'in the gene pool'. In general, there is a genetic susceptibility to various diseases & disorders.

Then why are there so many diseases and disorders listed and still growing.

As I said before, if selection is no longer acting on them, then in evolutionary terms they are no longer problems, although the individuals concerned might prefer not to have them.

If it is not a problem in evolutionary terms then why do papers say that the human condition will deteriorate? In evolutionary terms that would mean less fit humans. It may not get to the point of threatening extinction but it may mean a sicker species.

You make it sound like the pace of "modern life technology and industry" preventing selection weeding out the mutations which, thanks to modern life, technology, and industry, are no longer a fatal problem, is a bad thing; but it's a good thing - if you think saving lives and enabling people to have families is good. 'Weeding out' mutations by selection, in the short term, means death.

Modern technology is both a good and bad thing. Once again what do the papers mean when they say that it is the technically advanced nations that are and will suffer a deterioration in the human condition due to the accumulation of slightly deleterious mutations.

Why do you suppose technology and industry are working so fast to develop Covid19 treatments and vaccines? Hint: it's to slow down the activity of selection on the population; IOW to save lives.

Yes, but it also allows the bacteria and viruses to find ways to mutate and become more potent. It seems we still haven't found a way to treat past viral infections like SARS. So we are adding to the list of viral infections and natural selection is not weeding them out either.

And the idea that selection can weed out 'new pathogens and mutagens' is incoherent - what did you mean?

I mean the genetic damage that causes conditions like cancer and other diseases. Why do the papers talk about all diseases and disorders caused by things like pollution, contaminates, infections, etc. have a genetic basis? So, if modern life is continually introducing situations that cause mutations faster than natural selection cannot keep up. If modern tech and medicine find ways of reducing the effects of the harms of these conditions and don’t really get rid of them completely then they are passed onto future generations and slowly accumulate.

My bad, I meant certain types of diseases and disorders, but that misses my point - An increase in certain types of diseases and disorders doesn't mean an overall increase in diseases and disorders.

Whether there has been an increase in new diseases and disorders or an increase in identifying existing or certain ones I think overall humans have a lot of disorders and diseases which are having a detrimental effect. Relating this back to the OP it seems many have stemmed from human activity and lifestyle and this will only get worse.

 

[stevevw]

That's what I said - an equilibrium is reached. This is simply how evolutions work. Modern technology and medicine has simply moved the equilibrium point slightly to our short-term advantage. On the other hand, the resulting damage to the environment will probably more than redress the balance in lives lost in the long term if things don't change significantly...

Some may call it an equilibrium in survival terms but I don't think it is a good balance as far as the health of humans and the prospects for future human fitness if the trend continues.

If the change to the phenotype is not sufficient for selection to act on them, then they're not evolutionarily significant changes, by definition.

Not at the moment but maybe in the future.

Epigenetic changes are not mutations.

Not according to several papers. They say that disease-causing mutations can stem from changes in the epigenome. Besides as far as making humans more susceptible to diseases and disorders I don't think it matters. The diseases or susceptibility to diseases can be inherited so it must leave its mark on the genome somehow. Changes in the expression of genes is also a genetic change that can cause diseases and disorders in humans. These are mostly caused by lifestyle.

Genetic causes for human disorders are being discovered at an unprecedented pace. A growing subclass of disease-causing mutations involves changes in the epigenome or in the abundance and activity of proteins that regulate chromatin structure.
In another class of diseases, genetic mutations can cause loss of the function of proteins involved in epigenetic processes, such as modifying DNA methylation, chromatin remodeling, or histone posttranslational modifications, with phenotypic consequences resulting from altered epigenetic states at one or more loci.
The genotype-phenotype studies of the clinical disorders described in this section shows that almost all of the genomic imprinting disorders can be caused by a mixture of genetic or epigenetic abnormalities, either de novo or inherited.
Epigenetics and Human Disease

Chimpanzees rarely get cancer or a variety of other diseases that commonly arise in humans, but their genomic DNA sequence is nearly identical to ours. So, what's their secret? Researchers reporting in the September issue of the American Journal of Human Genetics, a Cell Press journal, has found that differences in certain DNA modifications, called methylation might play a role.

The researchers discovered hundreds of genes that display different patterns of methylation between the two species. These different patterns of methylation lead to different levels of expression and many of the genes involved are linked to specific human diseases. Given that environmental factors can affect DNA methylation, these results might help researchers to better understand how differences in genetics and environmental exposure contribute to differences, including different disease vulnerabilities, between the two species.

In addition, differentially methylated genes showed striking links with specific neurological and psychological disorders and cancers to which modern humans are particularly susceptible, suggesting that changes in DNA methylation might be linked to the evolution of humans' vulnerability to certain diseases.
New insights into why humans are more susceptible to cancer and other diseases

Isn't cancer caused by mutations? Though cancer is the result of an aging population many cancers are increasing because of lifestyle. This includes Gastrointestinal cancers associated with diet, Obesity leads to several types of cancers, skin cancer with temperature rises, sexually transmitted diseases from cancer like HPV which is associated with 40 different mutations.

The Three Reasons So Many People are Getting Cancer (Op-Ed)
The Three Reasons So Many People are Getting Cancer | Live Science

The number of new cancer cases is on the rise globally. This is mainly due to two factors: people are living longer and exposure to risk factors is growing. Low- and middle-income countries will face the highest increase in cancer rates unless the exposure to risk factors is reduced.
WHO | Key statistics

You have yet to show any evidence that our modern lifestyle choices are causing mutations that are responsible for the increase in 'lifestyle' disorders and diseases.

If diseases and disorders have a genetic basis whether that be by mutational changes or changes in the expression of genes and there has been an increase in diseases and disorders due to modern lifestyle isn't that evidence.

 

[quaternion]

it's a double edged sword

 

[FrumiousBandersnatch]

I am not a biologist or a geneticist but have studied these areas for years and done some units covering this at University.

If we're measuring credentials, I have been a working human biologist and spent 4 years getting a degree in the subject, an unpleasant amount of which involved genetics.

I also have commentary from other experts to go by and they are clear about what the papers are saying. Yes, some sensationalize things, but you can still get the basic gist of what is being said. That seems to be that modern life has brought about more situations that subject humans to genetic changes and relaxation of natural selection that can potentially cause problems for humans.

As I said, you've not shown evidence that more mutations are occurring, and evolution is the process by which selection pressures are blunted over time. Speculation about the possible future implications of keeping people alive and relatively healthy today is well and good, but we have more pressing existential threats to consider.

Logic also tells us that humans carry a lot of diseases and disorders.

No, it doesn't. Empirical methods tell us the disease load, and they tell us it has decreased very significantly in the developed world. What 'a lot' means is relative and you've provided no referent.

The point is most diseases and disorders have an agenetic base and therefore this signifies genetic damage. This is not diminishing and if anything seems to be increasing. Whether this is because of an actual increase or existing diseases and disorders being identified I would say both. But there is definitely an increase in mental illness and intellectual disabilities.

I'm sorry your years of study have produced so little understanding.

Then why are there so many diseases and disorders listed and still growing.

I already explained this.

If it is not a problem in evolutionary terms then why do papers say that the human condition will deteriorate? In evolutionary terms that would mean less fit humans. It may not get to the point of threatening extinction but it may mean a sicker species.

'Sicker' is not a term that has a well-defined meaning in an evolutionary context. If selection pressures reduce, more individuals survive to reproduce, i.e. 'absolute' fitness increases. That may or may not be good for the species, depending on the context, the timescale, and the definition of 'good' that you choose.

... what do the papers mean when they say that it is the technically advanced nations that are and will suffer a deterioration in the human condition due to the accumulation of slightly deleterious mutations.

I really don't know - in what way are those mutations evolutionarily deleterious if they are not acted on by selection?

Yes, but it also allows the bacteria and viruses to find ways to mutate and become more potent. It seems we still haven't found a way to treat past viral infections like SARS. So we are adding to the list of viral infections and natural selection is not weeding them out either.

Not really. Bacteria and viruses mutate constantly whatever we do. Vaccines don't make viruses mutate to become more potent.

Can you explain how you think natural selection could weed out viral infections?

I mean the genetic damage that causes conditions like cancer and other diseases.

That's a non-sequitur. I asked you what you meant by the idea that selection can 'weed out new pathogens and mutagens'. Genetic damage is neither pathogen nor mutagen.

Why do the papers talk about all diseases and disorders caused by things like pollution, contaminates, infections, etc. have a genetic basis?

I don't think they do, because that's only true to the extent that all biological events can be said to have a genetic basis; i.e. it's meaningless. I think you've misinterpreted what they do say.

So, if modern life is continually introducing situations that cause mutations faster than natural selection cannot keep up. If modern tech and medicine find ways of reducing the effects of the harms of these conditions and don’t really get rid of them completely then they are passed onto future generations and slowly accumulate.

You've presented no evidence that modern life is causing mutations faster. And if mutations occurring at the normal rate accumulate because we've reduced specific selection pressures, meaning they're no longer significantly deleterious, what's the problem? You'd rather those people suffered and died?

I think overall humans have a lot of disorders and diseases which are having a detrimental effect.

Sure, there are more diseases and disorders than we would like - but the overall incidence and burden of diseases and disorders has reduced enormously in the developed world over the last 200 years (life expectancy has doubled), and with it, the harm caused to individuals in those populations.

Relating this back to the OP it seems many have stemmed from human activity and lifestyle and this will only get worse.

The incidence of some diseases and disorders has increased due to 'lifestyle' factors, but to suggest it will 'only get worse' is certainly wrong. It will probably get worse in the short term. But this is more a socio-cultural problem than a genetic problem.