chapter 9

9.4 Which genomes are larger, those of chloroplasts or those of mitochondria? How does your genome compare with that of yeast in overall size and gene number?

Virtually all eukaryotic cells contain mitochondria, and in addition, plant cells contain chloroplasts. Although the genomes of organelles are independent of the nuclear genome, the organelles themselves are not. Many genes in the nucleus encoded proteins required for organelle function. The complete genomic sequence of many microbial eukaryotes has also been determined, and the number of genes ranges from 1000 (less than many bacteria) to 60,000 (more than twice as many as humans).

Pathogenicity island

a bacterial chromosome region of foreign origin that contains clustered genes for virulence

Ortholog

a gene in one organism that is similar to a gene in another organism because of descent from a common ancestor (see also paralog)

Metagenome

the total genetic complement of all the cells present in a particular environment

Interactome

the total set of interactions between proteins (or other macromolecules) in an organism Metabolome the total complement of small molecules and metabolic intermediates of a cell or organism

Translatome

the total set of proteins produced by an organism under a specific set of condition

Pan genome

the totality of the genes present in the different strains of a species

Proteome

(1) the total set of proteins encoded by a genome or (2) the total protein complement of an organism under a given set of conditions, also called the translatome

9.10 How does metaproteomics differ from proteomics?

Proteomics is the analysis of all the proteins present in an organism. The ultimate aim of proteomics is to understand the structure, function, and regulation of these proteins. The interactome is the total set of interactions between macromolecules inside the cell.

Chromosomal island

a bacterial chromosome region of foreign origin that contains clustered genes for some extra property such as virulence or symbiosis

Paralog

a gene whose similarity to one or more other genes in the same organism is the result of gene duplication (see also ortholog)

Open reading frame (ORF)

a sequence of DNA or RNA that could be translated to give a polypeptide

Nucleic acid probe

a strand of nucleic acid that can be used to hybridize with a complementary strand of nucleic acid in a mixture; one of the two strands is labeled.

Microarray

small, solid supports to which genes or portions of genes are affixed and arrayed spatially in a known pattern (also called gene chips)

Gene chip

small, solid supports to which genes or portions of genes are affixed and arrayed spatially in a known pattern (also called microarrays)

Transcriptome

the complement of all RNA produced in an organism under a specific set of conditions

Genomics

the discipline that maps, sequences, analyzes, and compares genomes

Proteomics

the genome-wide study of the structure, function, and regulation of the proteins of an organism

Metagenomics

the genomic analysis of pooled DNA or RNA from an environmental sample containing organisms that have not been isolated; same as environmental genomics

Systems biology

the integration of data from genomics and other "omics" areas to build an overall picture of a biological system

Hybridization

the joining of two single stranded nucleic acid molecules by complementary base pairing to form a double-stranded hybrid DNA or DNA-RNA molecule

Mobilome

the mobile genetic elements in a genome

Core genome

the part of a genome shared by all strains of a species

Codon bias

the relative proportions of different codons encoding the same amino acid; it varies in different organisms. Same as codon usage

Genome

the total complement of genetic information of a cell or a virus

Horizontal gene transfer

the transfer of genetic information between organisms as opposed to transfer from parent to offspring

Bioinformatics

the use of computational tools to acquire, analyze, store, and access DNA and protein sequences

9.13 How can systems biology be used to discover new diagnostic markers for disease?

By integrating multiple omics datasets in a systems biology approach, computer models predicting molecular activities and interactions in cells can be generated. For example, potential drug targets for the treatment of Mycobacterium tuberculosis have been identified using systems biology.

9.7 What are chromosomal islands? Why are they considered to be of foreign origin?

Comparison of the genomes of multiple strains of the same bacterial species shows a conserved component (the core genome) plus many variable genetic modules only present in certain strains of the species (combined with the core genome, this constitutes the pan genome). Many Bacteria contain relatively large inserts of foreign origin known as chromosomal islands. These contain clusters of genes that encode specialized metabolic functions or pathogenesis and virulence factors (pathogenicity islands).

9.2 How can protein homology assist in genome annotation?

DNA sequencing technology is advancing quickly. These advances have greatly increased the speed of DNA sequencing. Computer analysis of resulting sequencing data is also a vital part of genomics. Computational tools are used not only to annotate genomes but also to analyze sequences and the structures of biological macromolecules.

9.5 What is the major difference in how duplications have contributed to the evolution of the genomes of prokaryotic and eukaryotic cells?

Genomics can be used to study the evolutionary history of an organism. Organisms contain gene families, genes with related sequences. If these arose because of gene duplication, the genes are said to be paralogs; if they arose by speciation, they are called orthologs.

9.9 Besides gene expression, what else can be assayed using gene chips?

Microarrays consist of oligonucleotide probes corresponding to genes or gene fragments attached to a solid support in a known pattern; mRNA, cDNA, or DNA can then be labeled and hybridized to the gene chip to determine patterns of gene expression or the presence or absence of specific organisms. RNA-Seq combined with sequencing of cDNA can be used to profile the entire transcriptome of an organism.

9.8 How do the human microbiome and mycobiome differ?

Most microorganisms in the environment have never been cultured. Nonetheless, analysis of DNA samples has revealed enormous sequence diversity in most habitats. The concept of the metagenome embraces the total genetic content of all the organisms in a particular habitat.

9.6 How can comparative genomics help identify horizontal gene transfer?

Organisms may acquire genes from other organisms in their environment by horizontal gene transfer, and such a transfer may even cross phylogenetic domain boundaries. The mobilome, which includes transposons, integrons, and viruses, is important in genome evolution and often carries genes encoding antibiotic resistance or virulence factors.

9.1 What is one discovery resulting from the availability of a microbial genome?

Small viruses were the first organisms whose genomes were sequenced, but now many prokaryotic and eukaryotic cellular genomes have been sequenced.

9.14 What percentage of the human genome is now predicted to have functionality in at least one cell type?

Systems biology can also be applied to personal medicine. Besides detecting genetic variants, disease risks can be predicted by profiling a person's genome, transcriptome, proteome, and metabolome.

9.11 How can single

cell genomics be used to address microbial dark matter?- Metabolomics profiles the complete set of metabolic intermediates produced by an organism. This analysis can determine active metabolic pathways and potential cross-feeding (one organism supplies a nutrient for another organism) in community samples. Q Why is investigation of the metabolome lagging behind that of the proteome? IV • The Utility of Systems Biology 9.12 With advances in molecular techniques, the genomes of single cells can be sequenced. Expression and protein profiles of single cells can also be determined. These techniques are instrumental for studying as yet uncultured microbes.

Sequencing

deducing the order of nucleotides in a DNA or RNA molecule by a series of chemical reactions

Homologs

genes related in sequence to an extent that implies common genetic ancestry; includes both orthologs and paralogs

Gene family

genes related in sequence to each other because of common evolutionary origin

9.3 Approximately how many genes are necessary for a microbial cell to have a free

living existence?- Sequenced genomes of Bacteria and Archaea range in size from 0.14 to 14.7 Mbp. The smallest are smaller than those of the largest viruses, whereas the largest have more genes than some eukaryotes. Gene content in prokaryotic cells is typically proportional to genome size. Many genes can be identified by their sequence similarity to genes found in other organisms. However, a significant percentage of sequenced genes are of unknown function.