Worm Breeder's Gazette 13(3): 18 (June 1, 1994)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

The Structure of the C. elegans Genome and Implications for Function.

Tom Barnes

Department of Biology, McGill University, Montreal, PQ H3 A1B1 Canada

In C. elegans, the existence of a centralized database of genetic map data and a reference physical map makes it possible to compare physical and genetic maps across the whole genome. The most useful way to compare these two linear measures is by means of Marey maps (WBG 12(3):24), as the varying relationship is readily displayed and maps using different markers can be displayed on the same, absolute, set of axes.

Previously, I had reported that such an analysis reveals clear distinctions between the X chromosome and the autosomes, and that each autosome possesses a metrically definable central region, which corresponds to the well-known autosomal clusters. These metrically defined clusters appear to have both precise endpoints and have roughly uniform rates of recombination across their length. Also, these lengths and rates were very similar between clusters. This suggested that the question of whether the genetic map reflects the actual distribution of genes or merely the effect of recombination suppression was answered in favour of recombination suppression. Here I present additional data that suggests that this is an incomplete answer.

Firstly, using revised Marey maps based on the latest physical data and newly cloned genes, the resolution of the maps has increased and supports the earlier results. Secondly, I examined cDNA distribution. Plotting the position of each cDNA gives a very uneven plot. Therefore I examined the distribution of YACs which were positive for different numbers of cDNAs (essentially the first derivative of the cDNA plot). This plot revealed a striking separation of YACs hit by cDNAs many times from those hit only a few times. This does not correlate trivially with YAC size. On the autosomes, the high-hit YACs preferentially live in the centres, while the low-hit YACs preferentially live on the arms. The X chromosome again was distinct: there was no preferential distribution of high-hit or low-hit YACs. The points of inflection (where the high-hit regions end) can be defined by a hit frequency which is the same for all autosomal clusters, again consistent with a similarity of properties between the different clusters. These endpoints correspond precisely to the ends of the metrically defined clusters. This strongly suggests that the recombination suppression and the higher gene density are linked, especially considering that the X shows neither feature. We know from the genomic sequence of the cluster on III that the gene density is extremely high there. In fact, intergenic material comprises <50% of the total (Wilson et al., 1994). I propose that the primary force acting on the clusters is for compactness. Secondly, I propose that crossovers, for reasons of DNA sequence composition, occur in sequences found preferentially in intergenic versus coding sequences. Thus compactness so reduces the amount of intergenic DNA in clusters that recombination occurs predominantly in the arms. Put another way, I propose that the distribution of genes on the genetic map does reflect the physical gene distribution, but the concomitant influence on DNA sequence further skews the genetic map. Consistent with this, the X chromosome has both a uniform distribution of genes and a uniform metric.

Given the preceding, there are two questions: What is the selective force governing centralized compactness on the autosomes, and why does it not exert its effects on the X? For question 1, it seems that it is indeed "clusters" which are selected, rather than "arms", as the physical and genetic lengths of the 5 autosomal clusters are within 20% of one another, while arms vary 3-fold in length. It's hard to imagine what might be gained by centralized compactness on the autosomes; however, a speculation along the lines of chromosome behaviour in cell division seems reasonable. As for question 2, there are several known differences between the biology of the X and the autosomes, for example meiotic recombination in hermaphrodites (as revealed by him mutants), and segregation of an unpaired X in male meiosis. There are also spatial differences between the autosomes and the X during meiosis (Albertson, 1993). Finally, mechanisms exist to measure X chromosome dose in both sexes. Thus perhaps the X would resemble the autosomes except for the constraints imposed on chromosomal organization by any or all of the above features. It remains unclear, however, how any of the above features might require or produce a uniform gene distribution on the X.