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When I browsed NCBI I saw a pattern: even if the chromosome sizes, number of genes, and number of proteins are different, GC% in chromosomes tend to be similar. The examples are linked below.

Yeast, Plasmodium falciparum

If you see Mitochondria genome it is not very similar to chromosome. Why all chromosomes tend adjust their GC% near to the average of total GC% Is there a specific reason related to metaphase of meosis?

to further clarify I have some images to help

enter image description here enter image description here

The chromosome size or genes in an organism are not adjusting near the average of their total but GC% does. It has only 3-2% (falciparum) or 3-4% (vivax) variation in GC%. It feel like its balancing like equalizer. Why?

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Just to clarify: are you asking why chromosomes of very different sizes each have an average GC content that is similar to the average GC content of the genome? –  dd3 Mar 6 '13 at 22:09
Yupp you got it... I just want to know why and how at any stage of evolution an organism like [plasmodium vivax] (ncbi.nlm.nih.gov/genome/genomes/35?details=on&) (43-47%) and faciparum (18-20%) (2 evolved types) try to maintain similar GC% in all chromosome (look a the links given the it feels all chromosomes are maintaining their GC% percent in chromosomes and they dont care for amount of genes or chromosome size) –  grvpanchal Mar 7 '13 at 0:46

4 Answers 4

As @dd3 points out, average GC% indicates a need for stability and coding regions or structural regions of the genome may need to be more stable. But the largest %GC in genomes are found in thermophiles - organisms which live in high temperature water - in hotsprings and undersea geothermal vents. This review mentions how some thermophiles can be found with 50% GC. The extreme thermophile Thermus thermophilus can have a GC% content of 69.4%.

But you are asking how does GC content get averaged out over the length of a large genome. The answer is variation and selection. When a gene needs to be more stable because of genomic function or because its trying to live in a hotter environment mutations that convert A/T to G/C base pairs will convey an incremental advantage to survival and will tend to be retained in the gene pool as long as no greater disadvantage to the mutation results. Over time and as the stability creates a greater advantage, GC % will migrate further and further away from the mean.

This works for both thermo-tolerance and because of the biofunctional constraints of being a telomere, centromere or a coding region - stability and coding constraints play against each other to converge on an optimal GC content in any given stretch of the genome.

Conversely most genomes have a GC content below 50% are migrating there because too much stability can have a cost as well. Breaking up the DNA helix for transcription and other cellular processes must go smoothly as well for example.

Coding regions are significant for bacteria (E coli is 89% coding sequence). For coding sequences, the genetic code is logically 50% GC on the average, but if you look at the actual codons in the diagram below you will see that except in the case of a single codon case (tryptophan, methionine) the third base always has a GC option, allowing for a GC content in the mid 60 percentiles. The constraint of allowing coding sequences to freely vary is only an approximation - in some cases substitutions to amino acids with GC rich codons might move the cieling up a bit. And the more frequent amino acids have the possibility of making 2 or 3 bases of their codon GC bases. Overall it would be remarkable to find a bacteria with GC% greater than 72%. Mutations and the requirements of proteins being coded for would simply not allow it.

genetic code

So: over evolutionary periods these GC mutations accumulate where they are helpful, even to the extent of 2/3 of the genome being GC pairs. The strongest selective force to accumulate a high average GC% for a genome is exposure of the genome itself to a high temperature environment.

Note that this thermo-stability argument doesn't count for many animals because they do regulate their body temperatures.

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I liked your line "stability and coding constraints play against each other to converge on an optimal GC content in any given stretch of the genome." It feels more suitable to my question. Can I get a reference journal please –  grvpanchal Apr 13 '13 at 8:38
Thanks. That thought is a commonly known idea and its rederivable in practice. Let me add to the answer above.. –  shigeta Apr 13 '13 at 19:15

To begin, one might ask "What is the advantage of higher GC content?"

Higher GC content is associated with higher stability of the DNA, and accordingly, people have suggested that this is important for protein-coding regions. It has been found that there are quite a few protein-coding regions in GC-rich regions, but I am not sure whether the converse is true, which is the important part.

If the converse is true, then one might look at the distribution of protein-coding regions across the chromosomes and correlate it with GC-content. If also the size of the protein-coding regions in a given chromosome is proportional to the size of the chromosome, then you would have a reason as to why the average GC content of each chromosome is similar.

However, I recognize that this is all very speculative. Does anyone have better ideas?

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I liked the idea of proportionality of chromosome protien coding size and genes.. thanks. Why this question made me think it is important to ask because evolution is with random mutation process and with new environmental conditions the orgamism evolves to form new genes & this will cause random huge variations but by looking at GC% information, though there might be huge variation in sequences of chromosomes, a life is conspiring to maintain an equilibrium in AT:GC ratio. life doesnt thinks It has to keep ATG at beginning and poly A tail end for gene. life just checks the equilibrium –  grvpanchal Mar 7 '13 at 1:37

Good answer from Daniel. I'd also add that there can be significant differences between chromosomal or nuclear DNA GC content and that of extra-chromosomal entities like mitochondrial and chloroplast genomes or (naturally occurring) plasmids. These DNAs have different constraints on them (replication, sub-cellular location, eg) and that may be reflected to some degree by a GC content different than that of the nuclear chromosomes.

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There is significant variation in genomic GC content, both between species and within an individual genome. An average GC content in the range of 35%-45% is common, although there are definitely organisms that fall outside this range. The plasmodium species you link to above is an example of extreme AT richness (low GC content), whereas some bacterial genomes have as much as 70% GC content or more.

For eukaryotic genomes, nucleotide composition is not uniformly distributed. Just because a genome has an average GC content of 40% does not mean you can select any 10kb region in the genome and expect that region to have +/-40% GC content. Rather, eukaryotic genomes are a mosaic of large regions which internally have a very uniform composition, but whose composition is quite different from flanking regions (isochores).

So although all the chromosomes of a particular organism may have similar average GC content, realize this is just an average and that nucleotide composition varies significantly throughout the genome.

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Thanks, I truly get nucleotide composition varies significantly (A:T:C:G changes) but still HOW GC% remains similar throughout all chromosomes. To further clarify vivax (V)(43-47% range) and faciparum (F)(18-20% range) are of same plasmodium family. Eg chr 11 of both have almost same size but their GC% percent fall in particular given range(V: 45:1%, F:19%). It feels like differently evolved organism are trying to maintain particular range of GC%. HOW? And journal reference would be much appreciated. –  grvpanchal Mar 1 '13 at 1:14

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