Adaptation, Evidence and the scientific method

A lot of discussion has happened about the scientific method in Biology, the importance of evidence etc. There have been lot of occasions where people have been speaking across each other on these issues. I found the above article helpful.

Would also invite @swamidass; @glipsnort; @dga471 etc to comment on whether it is accurate and fair.

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Molecular biology probably gives us the best glimpse of selection. We can directly test for selection at the DNA level by looking for conserved sequence, and we do see a difference in sequence conservation between functional DNA and ā€œjunkā€ DNA. We know that natural selection happens at the level of the genome, but the big question is how it affects organisms at the phenotypic level and what environment pressures are responsible for selection.

Perhaps the best examples of natural selection and adaptation are found with single allele phenotypes. These are traits that are caused by one gene (or even a few genes), such as blood type. My personal favorite example of well supported adaptation is fur color in pocket mice, which you can read about here. In this case, they were able to find 4 mutations in one gene that showed strong evidence for selection, and that gene is well known for skin and fur color in other species (including humans). They even did a survey of the mouse population and found that the allele for dark fur color is strongly selected for in areas that have black rocks.

The moral of the story is that we know selection is happening, but we can jump the gun in attributing specific changes to specific selective pressures. This is something that all evolutionary biologists need to be aware of and do their best to not fall into the trap of ā€œjust so storiesā€.

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That is a circular argument isnā€™t itā€¦ isnā€™t ā€œfunctionā€ defined based on sequence conservationā€¦ or atleast, the sequences that are ā€œconservedā€ are identified as having functionā€¦ The logic being that the sequence was conservedā€¦ because of natural selectionā€¦ and since it has been conservedā€¦ itā€™s functionalā€¦ Because selection wouldnā€™t act on a ā€œnon functionalā€ sequence.

I agree selection happens. It has toā€¦ there must be some traits which give reproductive advantage in every organism given any set of circumstancesā€¦ or else the organism would go extinctā€¦

Nope. This is not how function is defined. It is sometimes used as one way, among many others, to infer function.

That has little to do with biology, and Iā€™m not sure it is Even true.

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Ok fair enoughā€¦ what are the other ways of defining functionā€¦ in these alternative definitionsā€¦ are the sequences defined as functional always conservedā€¦
This can get confusing because of the controversy following the ENCODE programme. As far as I understand, around 8% of the genome is conserved in human beings. While encode claims biochemical function for around 80% based on criteria which many evolutionary biologists disagree with. Following the ENCODE findings, there was paper critiquing it and claiming only maximum of 8%* can be functional because only that % is conserved.

*The 8% figure is based on memory.

Functional is as fuzzy and multifaceted a word as design. It was confusing long before ENCODE. The conflicts here arise from treating different uses of the same word as if they are identical. They are not.

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We can do gene knockout (i.e. stop the gene from functioning) studies to determine if a gene is important for function, so it is possible to determine function outside of sequence conservation. Of the genes we know are important for fitness we see patterns of sequence conservation. On the flip side, sequences that we know can be removed without causing a change in fitness show no signs of sequence conservation.

I tend to look at it from the other direction. Selection has to happen because there isnā€™t enough food to go around and often not enough mates to go around. There will be winners and losers, and in the long term the winners and losers will be determined by heritable traits. This is the idea that Darwin borrowed from Malthus who noticed a similar trend in economics and limited resources.

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@T_aquaticus,

Darwin doesnā€™t even have to be mentioned.

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I agree. ā€œDarwinā€ ends up confusing a whole mess of other issues extrinsic to the science. He did have a lot of great contributions, but modern evolutionary science is just differnet.

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As far as I know, gene knockout studies have been done mainly in yeastā€¦ and in the yeast cell, a large percentage of the genome is functional based on knockout studies(approx 90%) Do you have any data on what percentage of the sequences were conserved?

Except thatā€™s not how evolution works in the long term. Itā€™s not just individuals, itā€™s entire populations and species.Besides selection requires a variety of traits to work onā€¦ And how the trait shows up is often a question mark. There is definitely a lot more going on.

No see below

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I donā€™t think these are gene knockout studiesā€¦ Gene knockout study involves stopping the function of genes in various combinations to try and identify which are essential for function of the organism.
Currently as far as I know, this has been done for the entire genome of yeast. I have read newspaper articles of possible knockout studies in human cellsā€¦ though I am yet to see a published paper.
The article is definitely interestingā€¦ and a little concerning.

Howā€™s this:

https://www.scientistlive.com/content/flexible-and-precise-control-gene-expression

CRISPR can do knockdowns very easily. We donā€™t know on this case what the editing was, but there is no reason to doubt that knockdowns are being done in humans. Weā€™ve already done it in just about every model organism.

Sureā€¦ I have not shown any doubt that it will happen with humansā€¦ I just mentioned that I havenā€™t come across any published work on it and so am not aware.

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The ethics of performing human gene knockout work tends to limit the research in Western nations. One can work on human cell lines and embryos up to a certain stage but thatā€™s it. Even work on chimps and other primates may can run up against animal experimentation guidelines.

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I hadnā€™t realized that the brewerā€™s yeast genome is perhaps the first eukaryotic genome that was fully sequenced. I will add that to the memory banks.

Your numbers seem to jive with the information I am able to find.

" Yeast has a high signal-to-noise ratio, with protein-coding regions comprising approximately 70% of the genome, and regulatory elements comprising perhaps about 15% of the intergenic regions. The human has a much lower signal-to-noise ratio, with the corresponding figures being perhaps āˆ¼2% and āˆ¼3%[7]."
Kellis et al. (2003)

They identified these protein coding regions and regulatory regions through sequence conservation between 4 yeast species, so it appears that at least 85% of the yeast genome is under selective pressure. I donā€™t know if they included introns in these figures, but it is fair to say that the vast majority of the yeast genome is functional.

Scientists have also done a lot of work in mice. I donā€™t have any references handy, but I know from my own reading and experience that there are a lot of gene knockout strains of mice out there. These are used in all sorts of studies, from cancer research to infectious disease research. If you are ever curious, you can go here and type in the gene of interest to see if that company has a mouse strain with that gene knocked out.

When I say that there are winners and losers it requires a population, so population genetics is inherent in the description. As to new variants, the process of mutagenesis is well understood so that isnā€™t much of a mystery.