Gene structure and function Nabil bashir Fall, 2015

Introduction: Is it a simple one-to-one correspondence between genes and proteins,? Is the 25,000 genes sufficient to account for the vast array of functions that occur in human cells. Are the 2 copies of a gene on an autosomal chromosome expressed and generate product? Are different chromosomes have the same amount of genes? Are genes the same size on different chromosomes? Do genes have the same number of exones and intrones? Are all human genes authentic? Are there genes that do not produce proteins?

Alternative coding segments : the 25,000 human genes can encode as many as a million different proteins Combinatorial nature of gene networks : They form elaborate networks of functions, involving many different proteins and responding in a coordinated fashion to many different genetic, developmental, or environmental signals.

For genes located on the autosomes, there are two copies of each gene, one on the chromosome inherited from the mother and one on the chromosome inherited from the father. For most autosomal genes, both copies are expressed and generate a product. There are, however, a small number of genes in the genome that are exceptions to this general rule and are expressed only from one of the two copies. Examples of this unusual form of genetic regulation, called genomic imprinting,

.The Central Dogma: DNA → RNA → Protein The informational relationships among DNA, RNA, and protein are depndent structure of genes in the genome is a foundation for discussion of the genetic code, transcription, and translation.

Gene structure promoter region exons (filled and unfilled boxed regions) +1 introns (between exons) transcribed region This slide shows the structure of a typical human gene and its corresponding messenger RNA (mRNA). Most genes in the human genome are called "split genes" because they are composed of "exons" separated by "introns." The exons are the regions of genes that encode information that ends up in mRNA. The transcribed region of a gene (double-ended arrow) starts at the +1 nucleotide at the 5' end of the first exon and includes all of the exons and introns (initiation of transcription is regulated by the promoter region of a gene, which is upstream of the +1 site). RNA processing (the subject of a another lecture) then removes the intron sequences, "splicing" together the exon sequences to produce the mature mRNA. The translated region of the mRNA (the region that encodes the protein) is indicated in blue. Note that there are untranslated regions at the 5' and 3‘ ends of mRNAs that are encoded by exon sequence but are not directly translated. mRNA structure 5’ 3’ translated region

The (exon-intron-exon)n structure of various genes Some (very few) genes do not have introns. One example is the histone genes, which encode the small DNA-binding proteins, histones H1, H2A, H2B, H3, and H4. Shown here is a histone gene that is only 400 base pairs (bp) in length and is composed of only one exon. The beta-globin gene has three exons and two introns. The hypoxanthine-guanine phosphoribosyl transferase (HGPRT or HPRT) gene has nine exons and is over 100-times larger than the histone gene, yet has an mRNA that is only about 3-times larger than the histone mRNA (total exon length is 1,263 bp). This is due to the fact that introns can be very long, while exons are usually relatively short. An extreme example of this is the factor VIII gene which has numerous exons (the blue boxes and blue vertical lines).

The (exon-intron-exon)n structure of various genes histone total = 400 bp; exon = 400 bp b-globin total = 1,660 bp; exons = 990 bp HGPRT (HPRT) This figure shows examples of the wide variety of gene structures seen in the human genome. Some (very few) genes do not have introns. One example is the histone genes, which encode the small DNA-binding proteins, histones H1, H2A, H2B, H3, and H4. Shown here is a histone gene that is only 400 base pairs (bp) in length and is composed of only one exon. The beta-globin gene has three exons and two introns. The hypoxanthine-guanine phosphoribosyl transferase (HGPRT or HPRT) gene has nine exons and is over 100-times larger than the histone gene, yet has an mRNA that is only about 3-times larger than the histone mRNA (total exon length is 1,263 bp). This is due to the fact that introns can be very long, while exons are usually relatively short. An extreme example of this is the factor VIII gene which has numerous exons (the blue boxes and blue vertical lines). total = 42,830 bp; exons = 1263 bp factor VIII total = ~186,000 bp; exons = ~9,000 bp

Structural Features of a Typical Human Gene a gene as a sequence of DNA in the genome that is required for production of a functional product, be it a polypeptide or a functional RNA molecule. A gene includes not only the actual coding sequences but also adjacent nucleotide sequences required for the proper expression of the gene—that is, for the production of a normal mRNA molecule, in the correct amount, in the correct place, and at the correct time during development or during the cell cycle.

Pseudogenes: DNA sequences that closely resemble known genes but are nonfunctional Pseudogenes are widespread in the genome and are of two general types, processed and nonprocessed.

Nonprocessed pseudogenes are thought to be byproducts of evolution, representing “dead” genes that were once functional, having been inactivated by mutations in coding or regulatory sequences. In some cases, as in the pseudo–α-globin and pseudo–β-globin genes, the pseudogenes presumably arose through gene duplication, followed by the accumulation of numerous mutations in the extra copies of the once-functional gene

processed pseudogenes are pseudogenes that have been formed, not by mutation, but by a process called retrotransposition, and reverse transcription , and finally integration of such DNA copies back into the genome. Because such pseudogenes are created by retrotransposition of a DNA copy of processed mRNA, they lack introns and are not necessarily or usually on the same chromosome (or chromosomal region) as their progenitor gene.

Noncoding RNA Genes Not all genes in the human genome encode proteins. Chromosome 11, for example, in addition to its 1300 protein-coding genes, has an estimated 200 noncoding RNA genes, whose final product is an RNA, not a protein. Although the functions of these genes are incompletely understood, some are involved in the regulation of other genes, whereas others may play structural roles in various nuclear or cytoplasmic processes.

microRNA (miRNA) genes : An important class of noncoding RNA genes , of which there are at least 250 in the human genome; miRNAs are short 22-nucleotide-long noncoding RNAs, at least some of which control the expression or repression of other genes during development.