Computational tools and Interoperability in Comparative ... - CBS

Tools for Comparison of Bacterial Genomes 74
base composition in a Base Atlas). Such specialized atlases are explained in detail in a book that
we recently produced (Ussery et al., 2008).
As can be seen in > Fig. 2, the genes in this chromosome are strongly favoring one strand:
the positive strand for the first (right) half and the negative strand for the second (left) half of
the chromosome. These happen to be the leading strand during replication. Replication starts
at the origin, (the 12 o’clock position here), and proceeds on either side along the circle with
both a leading and lagging strand until the bubble reaches the terminus, at 6 o’clock, and the
ends are combined. The positive strand represented by a genome sequence is the leading
strand but only for the first half up till the terminus. Reading across the terminus along the
sequence on the same strand one enters the lagging strand. Gene preference for the leading
strand is a general feature for Firmicutes and for some other bacteria.
In > Fig. 2 the two outward lanes identify some regions with strong structural properties
(for instance the region around 2 o’clock, indicated by a black line). The observed strong
curvature (blue in the outward lane) where the DNA would easily melt (red in the second lane)
suggests this region contains genes that are highly expressed.
There are a number of global repeats, notably in the first quarter of the chromosome. Note
that the ribosomal RNA genes (light blue in the annotation lane) are located here, as indicated
by the arrows, and these are picked up as global repeats, as indeed they are repeated genes.
The GC skew lane shows the bias of G’s towards one strand or the other, averaged over a
10,000 bp window. In contrast to many Firmicutes with a strong GC skew, this genome only
has a weak GC skew (the right half is light blue and the left half is light pink). The innermost
circle colors the local AT content when it is more than three standard deviations distant from
the global average. Note a light red color around the 2 o’clock region: this local deviation in AT
content is related to the structural features located here.
The Genome Atlas of the Archaea Methanosarcina acetivorans, shown in > Fig. 3, tells a
different story. This strictly anaerobic organism so efficiently produces methane that it is held
responsible for virtually all biogenic methane. It can also oxidate CO to CO 2 (Lessner et al.,
2006). Strain C2A (the type strain of the species) was isolated from a marine sediment
(Galagan et al., 2002). Its genome is 5.7 Mbp long and contains 42.7% GC. The Genome
Atlas shows that its genes are evenly distributed over the two strands, and a GC skew is absent.
Instead, the lower quart of the genome contains many strong structural features. The genome
only contains three rRNA gene copies (indicated by arrows) one of which is located on the
negative strand (but as discussed above, this is actually the leading strand, as is preferred for
nearly all bacterial rRNA genes). Many other global repeats are visible, notably in the region
around 1.2 Mbp, which is strongly curved and easily melted, and is slightly more AT rich than
the rest of the genome. Here, the important carbon-monoxide dehydrogenase gene locus is
present, as are multiple transposases, which could be an indication of horizontally acquired
DNA. The genome is relatively poorly annotated, with many genes given as ‘‘predicted
protein’’ only, which is not uncommon for archaeal genomes.
In conclusion, a Genome atlas combines a number of features in one single figure that
summarizes a very long and detailed story about a chromosome or plasmid.
4 Whole Genome Alignment Methods
4319
Another way to compare genomes is based on alignment of nucleotide or amino acid
sequences. Sequence alignment is a common tool to identify similarities, with BLAST, for