C-Value 

 The C-value is the long-used term for the mystery, or paradox, of the wide range of genome sizes present among eukaryotes. They range from 13 Mbp (megabase pairs, 1.3 × 10⁷) for yeast to 1.7 × 10¹¹ bp for Amphiuma, or the mudpuppy, a urodele amphibian. The units used above, the number of nucleotide pairs in one haploid set of DNA, should be used consistently. In much of the literature, the amount of DNA per cell is expressed in picograms (1 pg is 9.8 × 10⁸ nucleotides), and the classic tables are often in error due to the limited accuracy of the methods used. The most accurate genome sizes are those for which complete nucleotide sequences are available; for example, the yeast genome has 13,105,020 bp (base pairs), give or take a small uncertainty because not all copies of repeated sequences  have been sequenced. The smallest bacterial genome accurately known from sequence is that of Mycoplasma genitalium, with 580,073 bp. Viruses have even smaller genomes, but they are not free-living and depend on their hosts for much of the required information. A part of the range in DNA content is apparently due to the different requirements of different species for genetic information, but that is not all there is to it, by any means.

The familiar fruit fly, Drosophila, is a complete animal, with all of the necessary structures, and it is not surprising that it has more DNA than yeast, which has an apparently simpler structure. The genome of Drosophila melanogaster is about 170 Mbp. It is easy to imagine that more genes and associated regulatory systems are needed to program the development and specify the complex structure of an animal. That is clearly true, but life is not so simple. The yeast genome has little space between its genes and almost no introns, and it is this compactness of organization that accounts for the relatively small size of its genome. The Drosophila genome, and plant and animal genomes in general, do not share this very compact organization, although some are more compact than others. They typically have large intergenic spaces, and most of the genome is not made up of genes and regulatory systems and has no known function. Most mammals, including humans, have about 3 × 109 bp, and it is not obvious why we require 20 times more DNA than does Drosophila. Some believe it is required for the brain, but humans have no more DNA than do mice. It is not reasonable that the mudpuppy requires almost 50 times more genetic information than we do, and its large genome must have some other explanation. One might expect that the very large urodele genomes are burdened with repeated sequences, and they do have a larger fraction of repeated sequences (90%) than Drosophila (30%). That is not the only source of the large genome size, however, since the so-called single-copy DNA is also very large in absolute quantity in the large urodele genomes. The genome sizes of single-celled protozoa range from about 1.0 × 10⁹ to 1.0 × 10¹², but that information does nothing to reduce the mystery.

 The “C-value paradox” remains as paradoxical as when it was first observed. It is known that a more compact genome is typically more compact in many features, such as smaller introns and smaller amounts of repeated sequences. Natural selection forces controlling genome size must exist, but remain unknown. How genomes have evolved is not well known, but it seems that there have been events of growth, some due to doubling of the entire set of chromosomes, others due to increases in the interspersed repeated sequences. Extraordinary reductions in DNA have also occurred in some species, while closely related species have retained their large genomes. There is a correlation between genome size and cell size, but it is not known how the two are connected, although cell size does affect metabolic rates. All that can be said is that genome size is not a parameter that is understood, although it is nevertheless intimately connected with gene structure and organization. That mammals have a quite uniform genome size is evidence for selective forces that control the C-value. Some geneticists consider the extra DNA in large genomes as a possible limitation in searching for genomic and regulatory function and have favored organisms with relatively small genomes, such as the puffer fish (Fugu rubripes) and a weed (Arabidopsis thaliana). Of course, the small genomes do reduce the amount of work required to determine the complete genome sequence.