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comparative genomics

In document Microbiology (Page 121-123)

With genomic data, via DNA sequencing, becoming more easily available, it is becoming increasingly relevant to consider the whole of a microorganism rather than its individual genes. In this way subtle differences can be examined (for example, what makes Bacillus

anthracis the causative agent of anthrax compared to the genetically very similar Bacil­ lus cereus). The arrangement of genes relative to one another, their presence or absence,

Key Notes

Comparative The information available from completely and partially

genomics sequenced genomes allows comparison of gene function across phylum boundaries. The relatively small size of microbial genomes means that many more species have complete sequences compared with higher organisms.

Generalized The singular circular model of a Bacterial genome is

structure of the applicable to E. coli, but other bacteria have multiple

Bacterial genome chromosomes, some of which are linear. Genome size seems to be related to the organism’s ecological niche, with obligate intracellular pathogens having the smallest genomes and free-living organisms the largest. A prokaryote’s genome may include one or more plasmids, which can provide specialized genetic information for activities not normally associated with cell growth (e.g. antibiotic production). Eukaryotes and prokaryotes differ in the arrangement of genes. Relatively speaking, Bacterial genomes are composed mainly of genes, whereas regulatory systems for genes comprise most plant and animal genomes.

Generalized A typical Archaeal genome is very similar to that of a

structure of Bacterial one. Generally the chromosome is single and

Archaeal genome circular, of a similar size to the Bacteria and may be complemented by the presence of plasmids. However, Archaea have many genes and genetic systems in common with eukaryotes as well as Bacteria.

Eukaryotic Eukaryotes have many more chromosomes than prokaryotes

genomes (between 4 and 105 per cell) and do not generally have plasmids. Extrachromosomal DNA does appear in the form of the mitochondrial and chloroplast genomes, which are held outside the cell nucleus.

Related topics (C2) Prokaryotic diversity (H2) Eukaryotic cell structure (C6) The major prokaryotic (K3) Virus genomes

groups

(C7) Composition of a typical prokaryotic cell

SectioN F – ProKAryotic dNA ANd rNA metAboliSm

the sequence of the genes, and intergenic regions are all used not only to compare spe- cies of Bacteria, but also to examine more distant relationships, for example, between higher animals and microorganisms. The size of higher organisms’ genomes (the human genome is 3200 million bp (Mbp) has made widespread whole genome sequencing a task performed by a few consortia of public and private laboratories worldwide. However, the relatively small size of Bacterial and Archaeal genomes (3–8 Mbp) has led to the release of new complete genome sequences on an almost weekly basis. The way in which DNA sequences are obtained and assembled into genome-sized pieces is beyond the scope of this text, but a primary consideration in approaching genomics is how the microorgan- ism’s genome is arranged. The structure of the viral genome is considered in Section K3.

generalized structure of the bacterial genome

The Bacterial genome is often portrayed as a stable, single, circular molecule. However, the genomes of most Bacteria are fluid (constantly changing in response to external stim- uli) and composed of several molecules including extra chromosomes, megaplasmids, and plasmids.

The model organism for molecular biology, Escherichia coli, is considered to be the para- digm for all Bacterial and Archaeal genomes. However, its single haploid circular chromo- some, consisting of around 4.6 million bp, is rather unusual compared with other genera, but is by far the best studied. Other Bacterial genomes comprise several chromosomes, some of which are circular and some of which are linear (Table 1).

The size of a Bacterial genome is related to the ecological niche in which the organisms live. Obligate pathogens, such as the causative agent of epidemic typhus (Rickettsia

Table 1. Chromosomal structures of Bacterial genomes*

(Total size bp) Number of circular chromosomes Number of linear chromosomes Extrachromosomal DNA

Escherichia coli (4 639 221 bp) 1 0 Plasmids may be present Mycoplasma pneumoniae (816 394 bp)

1 0 Some species in the

genus have a single plasmid

Rickettsia prowazekii

(1 111 523 bp) 1 0 No known plasmids

Paracoccus denitrificans

(~3 740 000 bp) 3 (2 + 1.1 + 0.64 Mbp) 0* Plasmids and megaplasmids may be present

Cupriavidus necator

(5 810 922 bp) 2 0 Plasmids may be present

Deinococcus radiodurans

(3 284 156 bp) 2 0 Plasmids may be present

Streptomyces coelicolor

(6 667 507 bp) 0 1 Linear and circular plasmids may be present

*An additional linear chromosome has been found in the closely related species Paracoccus

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F2 – GENOMES

prowazekii), seem to have minimized their genomes to such an extent that they rely on

host proteins and metabolites in order to replicate. This is taken to the extreme in the smallest known genome, that of Carsonella ruddii, which is composed of only 159 663 base pairs of DNA. In comparison, free-living organisms, such as the metabolically ver- satile Pseudomonas aeruginosa and Streptomyces coelicolor, have to cope with changes in temperature over tens of degrees, varying carbon and energy sources in the space of min- utes, and other environmental challenges. As a consequence they have a larger comple- ment of genes regulated by a more complex sensing apparatus, and thus a larger genome. Another strategy used by microorganisms to cope with transient environmental change is the acquisition of plasmids. Plasmids are small circular extrachromosomal pieces of DNA, which replicate independently of the genome. In contrast to the singular genome, there may be between 10 and 100 000 complete copies of a plasmid in a Bacterial cell. Plasmids may carry genes that allow the microorganism to become pathogenic (one of the main differences between species of Salmonella is the presence of plasmid(s) car- rying pathogenicity factors), resist antibiotics (resistance to kanamycin, streptomycin, and many other antibiotics may be carried on plasmids) or metabolize a particular set of compounds (for example, the proteins making up the xyl pathway used by Pseudomonas

putida for the degradation of toluene). Occasionally these plasmids are integrated into

the genome and only exist as extrachromosomal DNA in the presence of certain physi- ological stimuli. While the plasmids that are used in molecular biology are in the range of 2.5–10 thousand bp (Kbp), naturally occurring plasmids can be many hundreds of thou- sands of base pairs in size, bringing into question the philosophical difference between these megaplasmids and the chromosomes themselves.

The characteristics that distinguish Bacterial genomes from the eukaryotes lie mainly in how the genetic information is arranged. Relatively speaking, the Bacterial genome is information-rich, containing many regions coding for proteins and RNA but com- paratively few regions involved with the regulation of expression. Genes of similar func- tion tend to be clustered together, and often genes in a single metabolic pathway or all involved in the synthesis of a complex multi-subunit protein are found in operons (Sec- tion F4). Genes in an operon are sometimes so tightly packed together that they overlap. The fluidity of the Bacterial genome is reflected in gene order found in different Bacterial genera: there is no similarity in the arrangement of genes among the major phyla, and often gene order is very different in species of the same genus.

Different Bacterial genomes have varying composition in terms of nucleotides. The G+C content of the Bacteria ranges from 25 to 75%, and this is often reflected in the more frequent use of certain codons for certain amino acids (termed codon usage). While Bac- terial genomes do contain repeating elements, they are often long repeats of >10 bp and may be associated with pathogenicity islands, insertion sequences or the remnants of excised lysogenic bacteriophage.

In document Microbiology (Page 121-123)

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