HUMAN GENOME HUMAN GENOME Gene density 1100 kb

HUMAN GENOME

HUMAN GENOME Gene density 1/100 kb (vary widely); n Averagely 9 exons per gene n 363 exons in titin gene n Many genes are intronsless n Largest intron is 800 kb (WWOX gene) n Smallest introns 10 bp n Largest protein: titin: 38, 138 AA n

HUMAN GENOME Intronless Genes n n n n Interferon genes Histone genes Many ribonuclease genes Heat shock protein genes Many G-protein coupled receptors Some genes with HMG boxes Various neurotransmitters receptors and hormone receptors

HUMAN GENOME The human genome is the term used to describe the total genetic information (DNA content) in human cells. n It comprises two genomes, a complex nuclear genome, and a simple mitochondrial genome n

HUMAN GENOME Nuclear genome accounts for 99. 9995% of the total genetic information. n Mitochondrial genome accounts for the remaining 0. 0005% n

HUMAN MITOCHONDRIAL GENOME

HUMAN MITOCHONDRIAL GENOME The human mitochondrial genome is a single circular double-stranded DNA. n Complete nucleotide sequence has been established n

HUMAN MITOCHONDRIAL GENOME 16 569 bp in length n 44% (G + C). n The two DNA strands have significantly different base compositions: the heavy (H) strand is rich in guanines, the light (L) strand is rich in cytosines. n

HUMAN MITOCHONDRIAL GENOME H strand enriched in G L strand enriched in C

HUMAN MITOCHONDRIAL GENOME n n Very few repeats No introns 93% coding; Recombination not evident

HUMAN MITOCHONDRIAL GENOME The human mitochondrial genome contains 37 genes. n 28 are encoded by the heavy strand, and 9 by the light strand n

HUMAN MITOCHONDRIAL GENOME Of the 37 genes, 24 specify a mature RNA product: 22 mitochondrial t. RNA molecules and two mitochondrial r. RNA molecules, n The remaining 13 genes encode polypeptides which are synthesized on mitochondrial ribosomes. n

HUMAN MITOCHONDRIAL GENOME Mitochondrial codon table

HUMAN NUCLEAR GENOME The nucleus of a human cell contains more than 99% of the cellular DNA. n 23 (XX) or 24 (XY) linear chromosomes each of which has histones and other nonhistone proteins bound to it. n

HUMAN NUCLEAR GENOME n n n Introns in the most of the genes Genes are transcribed individually Repetitive DNA sequences (45%) Recombination at least once for each chrom. Mendelian inheritance (X + auto, paternal Y)

HUMAN NUCLEAR GENOME Chromosome 1 2 3 4 5 6 7 8 9 10 11 12 Size (Mbp) 249 237 192 183 174 165 153 135 132 132 123

HUMAN NUCLEAR GENOME Chromosome 13 14 15 16 17 18 19 20 21 22 X Y Size (Mbp) 108 105 99 84 81 75 69 63 54 57 141 60

HUMAN NUCLEAR GENOME Group A Chromosomes 1– 3 B 4, 5 C D E 6– 12, X 13– 15 16– 18 F G 19, 20 21, 22, Y Description Largest; 1 and 3 are metacentric but 2 is submetacentric Large; submetacentric with two arms very different in size Medium size; submetacentric Medium size; acrocentric with satellites Small; 16 is metacentric but 17 and 18 are submetacentric Small; acrocentric, with satellites on 21 and 22 but not on the Y

HUMAN NUCLEAR GENOME n n n Metacentric: Chromosome having its centromere in the middle Submetacentric: Chromosomes have short and long arms of unequal length with the centromere more towards one end Acrocentric: Chromosomes have a centromere very near to one end and have very small short arms.

HUMAN NUCLEAR GENOME Repetitive sequence n The human genome is occupied by stretches of DNA sequences of various length that exist in variable copy number. n These repetitive sequences may be in a tandem orientation or they may be dispersed throughout the genome. n Repetitive sequences may be classified by function, dispersal patterns, and sequence relatedness.

HUMAN NUCLEAR GENOME 1. Satellite DNA (tandem repeats) typically refers to highly repetitive sequences with no known function 2. Interspersed repeat sequences Typically the products of transposable element integration, including retrogenes and retropseudogenes of a functional gene.

HUMAN NUCLEAR GENOME Satellite DNA Microsatellites Minisatellites Macrosatellites

HUMAN NUCLEAR GENOME Microsatellites n Small arrays of short simple tandem repeats. n primarily 4 bp or less. n Different arrays are found dispersed throughout the genome, although dinucleotide CA/TG repeats are most common, yielding 0. 5% of the genome. n Runs of As and Ts are common as well. n Microsatellites have no known functions.

HUMAN NUCLEAR GENOME Minisatellites n Tandemly repeated sequences of DNA of lengths ranging from 1 kbp to 15 kbp. n For example, telomeric DNA sequences contain 10– 15 kb of hexanucleotide repeats. n Most commonly TTAGGG in the human genome, at the termini of the chromosomes.

HUMAN NUCLEAR GENOME Macrosatellites n Very long arrays, up to hundreds of kilobases, of tandemly repeated DNA.

HUMAN NUCLEAR GENOME Transposable Elements (Interspersed repeat sequences) Can be divided into two classes based on the mode of transposition; 1. The class I elements 2. The class II elements

HUMAN NUCLEAR GENOME 1. The class I elements 1. They are TEs which transpose by replication that involves an RNA intermediate which is reverse transcribed back to DNA prior to reinsertion. 2. These are called retroelements and include LTR transposons, non-LTR elements (LINEs and SINEs), and retrogenes.

HUMAN NUCLEAR GENOME n n 2. The class II elements Class II elements move by a conservative cut-andpaste mechanisms. The excision of the donor element is followed by its reinsertion elsewhere in the genome.

HUMAN NUCLEAR GENOME n n Integration of Class I and Class II transposable elements results in the duplication of a short sequence of DNA, the target site. There about 500 families of such transposons. Most of transposition has occurred via an RNA intermediate, yielding classes of sequences referred to as retroelements (more than 400 families, e. g. Alu, L 1, retrogenes, MIR). However, there is also evidence of an ancient DNA-mediated transposition (more than 60 families of class II (DNA) transposons, e. g. THE-1, Charlie, Tigger, mariner).

HUMAN NUCLEAR GENOME Retroelements n (LINEs) long interspersed repetitive elements and (SINEs) Short interspersed repetitive elements are the two most abundant classes of repeats in human. n Represent the two major classes of mammalian retrotransposons.

HUMAN NUCLEAR GENOME LINEs (long interspersed repetitive elements) n n n L 1, L 2, L 3 LINE is ~21% of human DNA A full-length LINE (or L 1 element) is approximately 6. 1 kbp There about 100000 copies of L 1 sequences in our genome. Approximately 1% of the estimated 3500 full-length LINEs have functional RNA polymerase II promoter sequences along with two intact open reading frames necessary to generate new L 1 copies.

HUMAN NUCLEAR GENOME SINE (Short interspersed nuclear elements) n Alu is ~10. 7% of human DNA n (1, 200, 000 copies) n MIR, MIR 3 is 3% of hum DNA (500, 000 copies) n Each Alu element is about 280 bp

HUMAN NUCLEAR GENOME LTRs (Long terminal repeats) n ERV and Mal. R are 8% of human DNA n (500, 000 copies)

HUMAN NUCLEAR GENOME n n n Class II elements contain inverted repeats (10– 500 bp) at their termini and encode a transposase that catalyses transposition. They move by excision at the donor site and reinsertion elsewhere in the genome by a non-replicative mechanism. MER 1 (Charlie), MER 2 (Tigger), others (350, 000 copies) 2. 8% of human DNA

HUMAN GENOME PROJECT n n The Human Genome Project is one of the most enterprising and challenging aspects of modern genetic research. Funded primarily by the US Government, This project was created to map and sequence the entire human genome--that is, to locate every gene on every human chromosome. It is estimated that anywhere from 100, 000 to 300, 000 genes exist! And scientists not only plan to map the genes, but also intend to sequence the 3 billion DNA amino acid “building blocks” that make each gene!

HUMAN GENOME PROJECT n n Human genome project was conceived in 1984 and begun in 1990. Human genome project draft completed in 2001. These drafts representing only 83 -84% of the entire genome. The Human Genome Project could easily be the most important organized scientific effort of mankind.

HUMAN GENOME PROJECT n n The project involves so many people, and not only geneticists; rather the Human Genome Project relies on all scientific and technological backgrounds from physics and chemistry to engineering and robotics to computer science. Even sociologists, ethicists, and theologians are involved. Never before in the history of humanity have so many professionals united under a single scientific endeavor. The estimated total cost of the Human Genome Project is a staggering $3 billion The US government provides most of the funds (other funds coming from big companies and other countries).