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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.

2 comments:

  1. Thank-you for your thought-provoking article, Jarle. You certainly have the capability to think way "outside the square". The OET hypothesis right or wrong,is very original and well worthy of consideration. I also share your reservations regarding Nick Lane's energy per gene argument. Never managed to really get my mind round that one. Maybe, as you suggest, because it is inherently flawed.

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  2. I am working with the theory, and I will eventually present it in a book. To give it some publicity, I first describe it here and I hope it is not so much "outside the square" that it can be accepted by a magazine that presents controversial articles. I am preparing an article for the magazine Skeptical. B.t.w. peer reviewing cannot be working when people like Nick Lane seems to have anything accepted. And his articles about mitochondria and the need for energy as the main thing are referred to as true by most scientists. Luckily we are not the only ones that have found the flaws in his articles. Since I wrote this I have seen that e.g. Michael Lynch and W. Ford Doolittle have also written critical comments.

    I have found on Amazon a most interesting book: The Intricacy Generator: Pushing Chemistry and Geometry Uphill. I wonder if you are the author? If so, is it also available as an e-book? I prefer that format. You can answer me on e-mail if you like. I use the domain "geneseque.com", and I use only my first name.

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