Mid-Range Inhomogeneity of Eukaryotic Genomes

Abstract

Multicellular eukaryotic genomes are replete with nonprotein coding sequences, both within genes (introns) and between them (intergenic regions). Excluding the well-recognized functional elements within these sequences (ncRNAs, transcription factor binding sites, intronic enhancers/silencers, etc.), the remaining portion is made up of so-called “dark” DNA, which still occupies the majority of the genome. This dark DNA has a profound nonrandomness in its sequence composition seen at different scales, from a few nucleotides to regions that span over hundreds of thousands of nucleotides. At the mid-range scale (from 30 up to 10,000 nt), this nonrandomness is manifested in base compositional extremes detected for each of four nucleotides (A, G, T, or C) or any of their combinations. Examples of such compositional nonrandomness are A-rich, purine-rich, or G+T-rich regions. Almost every combination of nucleotides has such enriched regions. We refer to these regions as being “inhomogeneous”. These regions are associated with unusual DNA conformations and/or particular DNA properties. In particular, mid-range inhomogeneous regions have complex arrangements relative to each other and to specific genomic sites, such as centromeres, telomeres, and promoters, pointing to their important role in genomic functioning and organization.

The early events underlying genome evolution in a localized Sinorhizobium meliloti population

“…The acquisition of this region by pSymA in the GR4-type isolates may have been mediated by exchange with the chromosomal region and further replication slippage [ 27 ]. These regions are considered to be sites of genetic instability [ 27 ] potentially relating to physiology and adaptation to particular environmental niches [ 28 ].

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“…Interestingly, we identified a pyrimidine/purine dinucleotide CT/GA-rich mid-range inhomogeneity (MRI) region in the isolates, covering 40 to 46 bp and located within an intergenic region of pSymA constituting a specific signature of the genome of this population. Regions of this type may promote the formation of non-canonical DNA conformations (A-DNA or triple-stranded H-DNA) that may lead to local irregularities in DNA structure [ 27 ]. This region, which probably originated from a shorter MRI (6 bp) conserved on the chromosome in S. meliloti and S. medicae may be a variant of ecological relevance, providing adaptation to particular environmental niches [ 28 ].…”

Adapting Biased Gene Conversion theory to account for intensive GC-content deterioration in the human genome by novel mutations

“…The mutation dynamics of novel and "old" alleles was studied for the least explored AC-rich regions-those chromosomal segments one DNA strand of which is predominantly composed by C and A nucleotides (the complementary strand is of cause TG-rich). These genomic regions have also distinctive DNA properties and their biological functions are only vaguely understood [13]. Table 5 shows that the frequency of various types of transitions and transversions inside AC-rich DNA strands may differ up to 2-3-fold from the average frequencies of these mutations over the entire genome (Table 1).…”

“…In addition, they include DNA sequences in which one strand is purine-rich, AC-rich, or highly periodic with alternating purine/pyrimidine sequences. We called these profound biases in nucleotide composition Genomic Mid-Range Inhomogeneity (or Genomic-MRI) [12,13]. Genomic-MRI regions may form special DNA structures (e.g., H-DNA, Z-DNA) and they are non-randomly distributed along the genome [14].…”

“…Genomic-MRI regions may form special DNA structures (e.g., H-DNA, Z-DNA) and they are non-randomly distributed along the genome [14]. At least some of them have well-documented biological roles [13]. Here, we have investigated Genomic MRI regions to quantitate the effect of mutations inside them.…”