1. What is a gene? Definition: A gene is a discrete unit of DNA (or RNA in some viruses) that encodes a nucleic acid or protein product that contributes to or influences the phenotype of the cell or the organism. Genes are the functional units of chromosomal DNA. Each gene not only encodes the structure of some cellular product, but also bears control elements (short sequences) that determine when, where, and how much of that product is synthesized. Most genes encode protein products; special classes of genes encode for RNA molecules. The way genes encode proteins is indirect and involves several steps. The first step is to copy (transcribe) the information encoded in the DNA of the gene as a related but single-stranded molecule called messenger RNA. Subsequently the information in the messenger RNA is translated (decoded) into a string of amino acids called a polypeptide. The polypeptides, on their own or by aggregating with other polypeptides and cell constituents, form the functional proteins of the cell.

2. Introns and exons Trying to pinpoint precisely what genes are is complicated by the fact that many eukaryotic genes contain mysterious segments of DNA, called introns, interspersed in the transcribed region of the gene. Introns do not contain information for functional gene product such as protein. They are transcribed together with the coding regions (called exons) but are then excised from the initial transcript. Since correct sequence in the introns (as well as in the regulatory region) is necessary in order to generate a properly sized transcript at the right time and place, introns (along with coding and regulatory regions) should be considered part of the overall functional unit, in other words, part of the gene

4. Schematic gene structure Generalized gene structure in prokaryotes and eukaryotes. The coding region (dark green) is the region that contains the information for the structure of the gene product (usually a protein). The adjacent regulatory regions (lime green) contain sequences that are recognized and bound by proteins that make the gene's RNA and by proteins that influence the amount of RNA made.

3. The average lenght of coding regions Estimates of the average length of polypeptide chains coded by genes of various organisms; these value have to be multiplied by 3 in order to obtaing the lenght of the corresponding coding DNA. Tipical values are 1,000 to 1,500 bp.

5. Number of introns-exons per gene Many eukaryotic genes contain mysterious segments of DNA, called introns, interspersed in the region of the gene. Introns do not contain information for functional gene product such as protein. Distribution of the number of exons among genes of three organisms

6. Genomes and genes The number of genes increases with genome size, but the trend is complicated due to repetitive DNA and introns. Counting genes is difficult, even in completely sequenced genomes

7. Average gene length Intron/exon statistics for various organisms

8. Plasmid genomes Bacterial cells isolated from nature often contain small DNA elements that are not essential for the basic operation of the bacterial cell. These elements are called plasmids. Plasmids are symbiotic molecules that cannot survive at all outside of cells. Even though plasmids are not part of the basic operational system of their host cells, some are quite complex, carrying many genes, so it is quite appropriate to refer to their distinctive DNA as a "plasmid genome." Bacterial plasmids often contain genes that are extremely useful to the bacterial host, for example, by promoting bacterial cell fusion, conferring antibiotic resistance, or producing toxins. Plasmids also are occasionally found in fungal and plant cells. Most are found inside mitochondria and chloroplasts, but some are found in nuclei or in the cytosol. Unlike the bacterial plasmids mentioned above, these eukaryotic plasmids seem to provide no benefits for their hoststhey seem to exist selfishly, only for the purpose of their own propagation. For their replication and maintenance, plasmids depend on the general cellular machinery encoded by the host genome. Bacterial plasmids are most often circular, but there are linear types too. In fungi and plants, linear plasmids are most common, but circular types are known in fungi.

9. Organellar genomes Mitochondrial and chloroplast chromosomes consist of double-stranded DNA molecules. Individual mitochondria and chloroplasts contain identical multiple copies of their chromosomes, and each eukaryotic cell contains several to many of these organelles. The organelle chromosomes contain genes specific to the functions of the organelle concerned. Nevertheless, most of the biological functions that occur inside these organelles are specified by genes in the nuclear genome. There is no overlap with the nuclear genome in gene content. Mitochondria and chloroplasts probably were originally prokaryotic cells that entered and took up a symbiotic relationship inside another cell. Throughout evolution most of the original prokaryotic genes were transferred to the nuclear genome or lost. Mitochondrial genomes can be eliminated in some organisms such as yeasts, but most organisms cannot survive without them, so there is still mutual interdependence between nuclear and organelle subdivisions of the genome. Chloroplasts can be eliminated only in photosynthetic organisms that can survive by taking in preformed nutrients from the environment (that is, that can act as heterotrophs).

10. Most eukaryotic DNA does not include genes Between genes there is DNA, mostly of unknown function. The size and nature of this DNA vary with the genome. In bacteria and fungi there is little, but in mammals the intergenic regions can be huge. Sequences of DNA that exist quite distant from a given gene can affect the regulation of that gene. They could thus be considered part of the functional gene unit, even though separated by long segments of DNA having nothing to do with the gene in question. In many eukaryotes some of the DNA between genes is repetitive, consisting of several different types of units repeated throughout the genome. Some of the repetitive DNA is dispersed; some is found in contiguous "tandem" arrays. Repetitive DNA is also found in some introns. The extent of this DNA is different in different species, and indeed there is variation of repeat number within species.

11. Comparing gene densities Schematic diagram of gene topography in four organisms. Light green = introns; dark green = exons; white = intergenic regions

12. A small fraction of total eukaryotic DNA is coding In mammals, only a few percent of the DNA is actualy coding:

13. Coding sequences are needles in the haystack It is apparent that the coding sequences are only a small part of the genome in most eukaryotes, particularly in human. Finding these regions is like finding a needle in the haystack. In addition, the genes are not uniformly distributed. There are regions in the genome where the genes are packed together, and regions where they are sparse, where finding genes is like finding water in a desert.

14. Categorizing the genes in eukaryotic genomes Classification schemes based on gene function suggest that all eukaryotes possess the same basic set of genes, but that more complex species have a greater number of genes in each category. For example, humans have the greatest number of genes in all but one of the categories used in the figure, the exception being ‘metabolism' where Arabidopsis comes out on top as a result of its photosynthetic capability, which requires a large set of genes not present in the other four genomes included in this comparison. This functional classification reveals other interesting features, notably that C. elegans has a relatively high number of genes whose functions are involved in cell-cell signaling, which is surprising given that this organism has just 959 cells. Humans, who have 1013 cells, have only 250 more genes for cell-cell signaling.

15. Overview of the human genome Genome size is approximately 3,200 Mb Gene number is approximately 30,000 Average gene density is 1 per 100 kb (5% of DNA encodes proteins); some areas are gene rich, others are gene deserts (0 to 64 genes per 100 kb) Average gene size (including introns) is 27 kb; gene regions account for about 25% of genome Average polypeptide size is 1.3 kb Fraction of genome with coding functions is about 1.5% At least 50% of genome made of transposable elements (e.g. LINES and Alus) Intron number ranges from 0 (in histones) to 234 (titin , a muscle protein). Hundreds of genes appear to have been transferred directly from bacteria to vertebrate genomes. Mechanism unknown. Functions have been assigned to 60% of genes. Largest human gene is dystrophin (mutated in muscular dystrophy): 2.5 Mb (larger than some bacterial genomes) 1077 blocks of duplicated regions in human genome (contain 10,000 genes): suggests genome rearrangements common in evolution