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Tuesday, February 28, 2017

Does the number of genes in an organism relate to the cell membrane area?

The question about energy in comparison to information processing has been treated by Nick Lane. It is relevant to compare the two, because in the same way as a computer needs energy for information processing, life also needs a lot of energy for processing data. And in the same way as energy consumption in computers depends on the technology, life uses variable amounts of energy for the various types of information processing. There are two types of such processing that are extensively used in life: DNA transcription to RNA and translation of mRNA to proteins. The latter is much more complicated and power consuming than the former.

But Nick Lane has introduced a strange concept: energy supply per gene. This is strange because a gene does not consume any energy. The energy consumption of a computer is not either dependent on the number of programs installed. It is the use of the programs that consumes energy. It is exactly the same with life. DNA in the cells does not consume energy at all, except when it is copied. And DNA is copied only when the cell is replicated. Energy is used for gene processing mainly when proteins are produced. Lane also states that, as he says:
"What we discovered is that there is an extraordinary energetic penalty for growing larger. If you were to expand a bacterium up to eukaryotic proportions, it would have tens of thousands of times less energy available per gene than an equivalent eukaryote. And cells need lots of energy per gene, because making a protein from a gene is an energy-intensive process. Most of a cell´s energy goes into making proteins."
As we see, Lane agrees with me that it is protein production that is energy intensive. But there is no direct relation between the number of genes and protein production. Genes are read when they are needed, and there could be lots of genes that are not read at all, especially in multicellular organisms. To find out how Lane reasoned when he came up with the concept "energy supply per gene" I will make an analysis of the article by Nick Lane where I fetched the former citation. It was found in New Scientist 23. June 2012: "Life: Inevitable or fluke?", where he also says:
"At first sight, the idea that bacteria have nothing to gain by growing larger would seem to be undermined by the fact that there are some giant bacteria bigger than many complex cells, notably Epulopiscium, which thrives in the gut of surgeon fish. Yet Epulopiscium has up to 200,000 copies of its complete genome. Taking all these multiple genomes into consideration, the energy available for each copy of any gene is almost exactly the same as for normal bacteria, despite the vast total amount of DNA. They are perhaps best seen as consortia of cells that have fused together into one, rather than a giant cells. So why do giant bacteria need so many copies of their genome?"
He here refers to a giant bacterium with a lot of genome copies. The argument is that to serve a large membrane area, more copies of the genome is needed. He then turns this argument around, to say that the more genes there are, the more membrane area is needed:
"So the problem that simple cells face is this. To grow larger and more complex, they have to generate more energy. The only way they can do this is to expand the area of the membrane they use to harvest energy. To maintain control of the membrane potential the area of the membrane expands, though they have to make extra copies of their entire genome - which means they don´t actually gain any energy per gene copy.
Put another way, the more genes that simple cells acquire, the less they can do with them. And a genome full of genes that can´t be used is no advantage. This is a tremendous barrier to growing more complex, because taking a fish or a tree requires thousands more genes than bacteria possess.
So how did eukaryotes get around this problem? By acquiring mitochondria. About 2 billion years ago, one simple cell somehow ended up inside another."
He was thinking of the bacterium that he assumes became the first mitochondrion. He further says:
"As the mitochondrial genome shrank, the amount of energy available per host-gene copy increased and its genome could expand." 
He must have thought that by reducing their genome size, but not the membrane area, the mitochondria would have a lot of membrane area "free" to support the genes in the nucleus. But it is not true that the more genes there are, the more membrane area is needed. Energy is only needed if the genes are expressed by producing proteins. There could have been lots of more genome copies. And in fact, there are a lot more copies before reproduction by cell fission, when the number of copies is halved.

So his argument is based on a dependence that does not exist, but he makes it even worse by transferring the alleged relation to eukaryotes. In eukaryotes even the first relation does not exist. There is no need for extra gene copies to serve more membrane area, because while bacteria express their genes directly after reading them, which gives limitations e.g. due to available volume. Eukaryotes stores a copy for multiple use, as mRNA is transported to where they are needed.

In that respect eukaryotes work more like computers do. Before a program is run it is copied from the disk to faster memory, where it can be run many times. An analogy to bacteria would be to execute the program directly from the disk. Then multiple disks would be needed to have enough processing capacity.

To show that eukaryotes really utilize the freedom of repetive expression of genes, I will refer to CELL BIOLOGY BY THE NUMBERS, which shows by an example that an eukaryote produces 10 times as much protein per mRNA. In addition we must of cause also count the extra limitation in bacteria when transcription rate is limited to the expression rate. But it seems that there is not a large difference in the speed of these two processes, also according to CELL BIOLOGY BY THE NUMBERS.

When Lane says that "the more genes that simple cells acquire, the less they can do with them. And a genome full of genes that can´t be used is no advantage.", then it is true under the following assumption: All genes should have a certain amount of expression to have a right of existence. He argues that "a fish or a tree requires thousands more genes than bacteria possess". This is correct, but here he compares to multicellular organisms that have a lot of genes that are expressed in certain cell types, and also genes that are used only in the development phase. The number of genes used in a certain cell under normal circumstances may even be less than in an average bacterium. What is interesting is however to compare bacteria to single celled eukaryotes.

Based on this NCBI source the average bacterium has 3000 protein coding genes and the average eukaryote has 10 000. If we assume that the ancient organisms had gene numbers comparable to what is in the lower range today, then we find an opposite trend. There are quite a few eukaryotes that have less than 100. On the other hand, very few of the sequenced bacteria have less than 1000 protein coding genes. Below 100 genes we hardly find any bacteria.

One reason there is today in average more genes in eukaryotes than in bacteria is that eukaryotes have a lot of variants of the same enzymes. This is much less common in bacteria, and if we did not count them, then the bacteria might have, also in average, had more genes than eukaryotes. That is because there are a lot metabolic enzymes that are not needed in many of the eukaryotes. They typically live in symbiotic relation with bacteria. We can just look at the vitamins that humans depend upon, but which are produced by intestinal bacteria. And when we are calculating the need for energy, then we should not count enzyme variants, because they are typically used under different conditions or, for multicellular organisms, in different cell types.

There is one more missing link in his argumentation. He argues that membrane area is needed because there is need for more energy. But that is true only for organisms that use membraneous electron transport chains in their energy metabolism. At anoxic conditions there is no need for such metabolic paths. All enzymatic reactions take place at substrate level, and energy supply is only dependent upon volume, not membrane area.

Lane also speculates how the first cells could have managed:
"The enzymes that powered the first life cannot have been as efficient, and the first cells must have needed a lot more energy to grow and divide - probably thousands or millions of times as much energy as modern cells."
Based on his conclusion about cell organization it is strange that he then assumes that life originated as bacteria. It would be much more according to his argumentation to conclude that life must have originated as eukaryotes.

While there is no relation between gene number and membrane area, the genome size may limit the reproduction time for cells. And even though there is no significant difference between gene number in bacteria and eukaryotes, the eukaryote size is normally very much larger. That is due to the non-expressed sequences, introns and spacers. But this is no limitation for eukaryotes. Actually, it is a limitation for bacteria, because they have only one position to start DNA replication. Eukaryotes have a lot of them, so they avoid this limitation.

Thursday, February 23, 2017

How to use the terms bacteria, archaebacteria, eubacteria, eukaryotes, prokaryotes, akaryotes

There are two types of life: eukaryotes and bacteria. And there are two types bacteria: eubacteria and archaebacteria. Eukaryotes are much more complex and contain a nucleus. Bacteria are alternatively denoted "akaryotes" to say that they do not have any nucleus. But also mature red blood cells are devoid of nuclei, and they are not bacteria. "Prokaryotes" has also been used as a name for bacteria, but that insinuates that they are older than eukaryotes, which we cannot know for sure. We do not need any of these confusing terms, but Woese created some confusion when he defined archaebacteria, eubacteria and eukaryotes as domains, and called them for short: "Archaea", "Bacteria" and "Eukarya". It is especially the name Bacteria that is confusing, because that is the same as what has traditionally been called eubacteria. It is not enough to use the capital letter to differentiate between Bacteria and bacteria. The latter is also sometimes used in the beginning of a sentence. In my meaning we do not need these confusing terms, and I will therefore only use the terms eukaryotes and bacteria, the latter consisting of eubacteria and archaebacteria.

OET, The Organelle Escape Theory

The Organelle Escape Theory is published here for the first time internationally. It was first published in Norwegian in Universitetsavisa. It is one of four possible sequences for the origins of eukaryotes, organelles and bacteria, as mentioned in my earlier blog post. There are many observations that have been used in support of the endosymbiosis theory. Most of them are based on similarities between organelles and bacteria. But there is no easy way to see direction from similarities, so based on similarities my theory is in fact supported equally with Margulis’ theory. The endosymbiosis theory has been interpreted to mean the occurrence of several events that were very improbable and occurred just once in history. But endosymbiosis is observed even today. That is in line with my theory, as it is fundamental in the theory that bacteria are commuting organelles that became more and more autonomous until they could survive without a host. In a few cases the process is not completed, however. E.g. some types of Rickettsia are still commuting organelles. But, as stated above, the theory is based upon missing evidence for the endosymbiosis theory as the only possibility.

Lynn Margulis and her endosymbiosis theory may not have been the scenario that nature followed

Lynn Margulis has been associated with endosymbiosis. She was not the first one to propose the idea. It was proposed several times in the period 1883 to 1927, involving Andreas Schimper, Konstantin Mereschkowsky and Ivan Wallin. None of them could prove the theory, and it was mostly rejected. It got new interest during the 1960s, however, as it was shown that these organelles contain DNA.  Hans Ris was the first to re-evaluate the idea,  but also Lynn Margulis became very interested in the theory. In 1967 she published an article in the Journal of Theoretical Biology. Concurrently there was also an article in Nature by Jostein Goks√łyr. It was however Margulis who became associated with the theory, and after a decade of aggressive fight it was accepted as more or less proven. Her victory was partly due to her stubbornness, but genetic research eventually came her to assistance.

The ruling theory at her time was that organelles were produced locally, and eukaryotes were generally held to be the product of bacteria. She pointed out that there are a lot of similarities between organelles and bacteria, and when DNA analysis became available in the 1970s, then it was shown that they are genetically related. The support for the theory increased, and there were several attempts to prove it. In 1982 Michael W. Gray and W. Ford Doolittle evaluated earlier attempts to prove the theory in the article:

"Has the Endosymbiont Hypothesis Been Proven?"

Here they showed that earlier attempt were not full proofs. Instead they made a new analysis based on two different kinds of chloroplasts (plastids). One of the central conclusions in this 42 page article is:

Taken at face value, this means that cyanobacteria and red algal plastids diverged from each other more recently than either did from Euglena (or Lemna) plastids and thus either that cyanobacteria evolved from plastids or (more reasonably) that the most recent common ancestor of Porphyridium and Euglena (Lemna) plastids was not itself a plastid, but an oxygen-evolving photosynthetic procaryote.  (my emphasis)

It is interesting to see that they mentioned the possibility that "cyanobacteria evolved from plastids". It does not seem that they gave this much weight, however. It is other reasons why they concluded that the endosymbiotic origin of at least one of the organelles was just nearly assured.

There are four possible sequences of the origin of eukaryotes, bacteria and organelles. Two of them have the bacteria as the original. In one of them bacteria became eukaryotes and these created organelles. That was the old theory. The other possibility is that bacteria were imported and became organelles. I illustrate them in this way:

 B->E->O Traditional theory

B->(O and E) Endosymbiotic theory

But eukaryotes could also be the original. In that case there is also two possibilities: They could have been reduced to bacteria, which subsequently created organelles. That is the theory proposed by Patrick Forterre and supported by Anthony M. Poole and David Penny, the thermoreduction theory. Another possibility is the one that Michael W. Gray and W. Ford Doolittle only mentioned as a theoretical possibility: that the eukaryote created both organelles and bacteria. The two possibilities are illustrated here:

E->B->O Thermoreduction theory

E->(O and B) Organelle Escape Theory, OET

I have called the latter Organelle Escape Theory because some of the organelles that were created got a commuting role, and among them there were many that became autonomous bacteria. OET, the "Organelle Escape Theory", which describes this scenario. It explains not only the origin of organelles, but also the origin of bacteria. The possibility mentioned above, that cyanobacteria evolved from plastids is a direct consequence of OET. When they say that this possibility is less reasonable, it is not based on any reasoning at all. I think it is very reasonabe. The conclusion of Michael W. Gray and W. Ford Doolittle should therefore have been that either the endosymbiosis theory or the Organelle Escape Theory is nearly assured. But if OET is chosen, then we do not have to say "nearly".

Monday, February 6, 2017

Contra-Darwinism

Neo-Darwinists believe that selection is a creative force that drives evolution. But there is a severe problem with this view. If there is some change that makes the organism better, then it will be maintained by selection. If there is a new improvement that can take place in one step, then that improvement will again be maintained by selection, and so on, until there is no more improvements possible. Evolution under hard selection pressure tends to stagnate at a suboptimal state. After a period at this state only deleterious changes are possible. There may be neutral mutations, but none of them lead to any improvement as the next stage, else they would have been tested already. What is needed for progressive evolution to proceed is a control system that can allow further improvement. By controlling selection this system can allow further trial-and-error. The key to progressive evolution is therefore the smartness of this control system. I have called it "the contra-Darwinistic system". Contra-Darwinism is not in conflict with Darwin’s theories, but I have called in contra-Darwinism because it is in conflict with the neo-darwinistic view that selection is a progressive force. By seeing selection as a maintenance force that has to be controlled to allow evolution, it is much easier to understand how biological systems can be improved to become very ingenious systems. And it is also possible to understand the creation of novelties in life. Contra-Darwinistic systems are present in various variants in different forms of life. Those that are most efficient are found in the organisms that have evolved in the most ingenious ways.

Evolution and intelligence

Intelligence is a result of evolution. That is a fact that nobody can deny. But was there some form of intelligence present already before the origin of life?  A lot of people prefer to answer this question with a "yes". There are a lot of different view on the question, but most of them belong to one of the groups "creationism", "Intelligent Design", "The Third Way" and neo-Darwinism.

All the various forms of creationism depend on a theistic force to drive evolution. Intelligent Design depends on a super intelligence that could predict everything so well that it could construct an initial form of life that would evolve according to readymade recipes stored in the cells of every organism. Lynn Margulis had another variant. She posited that bacteria forms an intelligent network. This network controls the evolution of all higher forms of life, i.e. eukaryotes, but also the conditions on the Earth surface. That follows from the Gaia theory that she launched together with James Lovelock. There is a group of scientists that have organized under the concept "The third way". Most dominating in the group are James A. Shapiro and Denis Noble. They have inherited a lot of Lynn Margulis’s thinking, probably also her bacterial intelligence theory.

Darwin did not refer to any intelligence, but he probably believed that life contains something that is not existing in non-life, and must have a theistic origin. He said that: "There is grandeur in this view of life, with its several powers, having been originally breathed by the Creator into a few forms or into one; and that, whilst this planet has gone circling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being evolved.”

Neo-Darwinists do not believe in intelligent control of evolution. I do not know what they think about the origin, as that is not a part of their theory. But instead of intelligent control, they posit that selection in some enigmatic way controls evolution.

If there is something in nature that is reminiscent of an intelligence or could be seen as an enigmatic control system, then it is the "contra-Darwinistic system". It is present in nearly all forms of life, and the better variants of the system is found in organisms that evolve better, i.e. have the most innovative evolution.