Today I was reading a paper entitled “Genomes in three dimensions” published by Monya Baker in Nature about two years ago. According to her commentary, we must study the chromosome structure to understand how a genome works, so that we must have data not only consisting of DNA sequences, but also genomes in three dimensions.
In particular, the commentary focussed on studies about three-dimensional structures of chromosomes coiled in the nucleus… since before scientists can really understand what sequencing data tell us, we have to study the chromosome interactions in the nucleus, the higher-order chromosome arrangements and the long-range looping interactions that bring gene sequences into physical contact with far-off regulatory elements.
We know, for instance, that inactive chromatin is generally located near the nuclear periphery, so that translocations of genes within chromosomal regions near the nuclear envelope may switch off them. At the same time, we know that long-range interactions can be altered by disease-associated mutations in stretches of DNA that do not code for genes.
This is true… and that is not the full story! We know that some chromosomal regions are more prone to rearrangement than others. Moreover, the evolution of genes is not necessarily the same on each chromosomes. For instance Singh (2005) showed that the comparison of the patterns of molecular evolution between autosomes and sex chromosomes (such as X and W chromosomes) can provide insight into the forces underlying genome evolution. In particular, he investigated the patterns of codon bias evolution on the X chromosome and autosomes in Drosophila melanogaster and Caenorhabditis elegans assessing that X-linked genes have significantly higher codon bias compared to autosomal genes in both flies and nematodes. Moreover, DNA sequences on X chromosomes often have a faster rate of evolution when compared to similar loci on the autosomes, as assessed by Meisel et al. (2012). Similarly, Mank et al. reported that evolution proceeds more quickly on gene located in the Z chromosome in birds (with ZZ males and ZW females), where hemizygous exposure of beneficial nondominant mutations increases the rate of fixation, as well as genes on the human X chromosomes evolved rapidly in comparison to genes located on autosomes (Kvikstad and Makova 2008). Finally, each chromosome may have differential evolution rates in diverse regions. Indeed, Casto and colleagues (2010) highlighted two X-chromosomal regions that are outliers relative to the rest of the human X chromosome with respect to the distribution of mutations suggesting that these loci were differentially influenced by selection in the past.
In the last years, several genome projects have been published without any kind of information about the localization of the annotated genes. Even if the availability of a wholly sequenced genome is a powerful tool to study the evolution of an organism, the absence of information related to the gene mapping (together with the absence of interest for gene mapping) makes genome projects less effective than someone think. What a missed opportunity!
Singh, N. (2005). X-Linked Genes Evolve Higher Codon Bias in Drosophila and Caenorhabditis Genetics, 171 (1), 145-155 DOI: 10.1534/genetics.105.043497
Meisel RP, Malone JH, & Clark AG (2012). Faster-X evolution of gene expression in Drosophila. PLoS genetics, 8 (10) PMID: 23071459
Mank, J., Axelsson, E., & Ellegren, H. (2007). Fast-X on the Z: Rapid evolution of sex-linked genes in birds. Genome Research, 17 (5), 618-624 DOI: 10.1101/gr.6031907
Baker, M. (2011). Genomics: Genomes in three dimensions Nature, 470 (7333), 289-294 DOI: 10.1038/470289a
Casto AM, Li JZ, Absher D, Myers R, Ramachandran S, & Feldman MW (2010). Characterization of X-linked SNP genotypic variation in globally distributed human populations. Genome biology, 11 (1) PMID: 20109212