Human genome
From Freepedia
The human genome is the genome of Homo sapiens. It is made up of 23 chromosome pairs with a total of about 3 billion DNA base pairs. The Human Genome Project produced a reference sequence of the euchromatic human genome, which is used worldwide in all of the biomedical sciences.
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Features
Chromosomes
Image:Human genome to genes.png There are 24 distinct human chromosomes, numbers 1-22 plus the sex-determining X and Y chromosomes. Chromosomes 1-22 are numbered roughly in order of decreasing size. Each somatic cell in a healthy individual has one copy of chromosomes 1-22 from each parent, plus an X chromosome from the mother, and either an X or Y chromosome from the father, for a total of 46.
Genes
It is currently estimated that there are 20,000-25,000 human protein-coding genes. Surprisingly, this is comparable (within a factor of 2) to the number of genes in several much simpler organisms, such as the roundworm and the fruit fly. However, human cells make extensive use of alternative splicing to produce several different proteins from a single gene, and the human proteome is much larger than those of the aforementioned organisms.
The estimate of the number of human genes has been repeatedly revised down from initial predictions of 100,000 or more as genome sequence quality and gene finding methods have improved, and it could continue to drop somewhat further.
Human genes are distributed unevenly across the chromosomes. Each chromosome contains a number of gene-rich and gene-poor regions, which seem to be correlated with chromosome bands and GC-content. The significance of these nonrandom patterns of gene density is not well understood.
In addition to protein coding genes, the human genome contains several thousand RNA genes, including tRNA, ribosomal RNA, and other non-coding RNA genes.
Regulatory sequences
The human genome has many different regulatory sequences which are crucial to controlling gene expression. These are short sequences that typically appear near and within genes. A systematic understanding of these regulatory sequences and how they together act as a gene regulatory network is only beginning to emerge from high-throughput expression and comparative genomics studies.
Junk DNA
Protein-coding sequence (specifically exons) comprise less than 1.5% of the human genome. Aside from genes and regulatory sequences, the human genome contains a vast amount of sequence the function of which, if any, remains unknown. This "junk" DNA in fact comprises the vast majority, by some estimates 97%, of the human genome size. Most of this is comprised of repeat elements and pseudogenes, but there is also a large amount of sequence that does not fall under any known classification. It is likely that further study will reveal presently unknown function for at least some of this sequence.
Variation
The great majority of human genetic variation is accounted for by single nucleotide polymorphisms (SNPs), which are substitutions in individual bases along a chromosome present in a significant fraction of the human population. Most analyses estimate that SNPs occur on average somewhere between every 1 in 100 and 1 in 1,000 base pairs in the euchromatic human genome, although they do not occur at a uniform density. Thus follows the popular statement that "all humans are at least 99% genetically identical", although this would be somewhat qualified by most geneticists. A large-scale collaborative effort to catalog SNP variations in the human genome is being undertaken by the International HapMap Project.
The genomic loci and length of certain types of small repetitive sequences are highly variable from person to person, which is the basis of DNA fingerprinting. The heterochromatic portions of the human genome, which total several hundred million base pairs, are also thought to be quite variable within the human population (they are so repetitive and so long that they cannot be accurately sequenced with current technology). These regions contain no genes, and it seems unlikely that any significant phenotypic effect results from typical variation in repeats or heterochromatin.
Most gross genomic mutations in germ cells probably result in inviable embryos; however, a number of human diseases are related to large-scale genomic abnormalities. Down syndrome, Turner Syndrome, and a number of other diseases result from nondisjunction of entire chromosomes. Cancer cells frequently have aneuploidy of chromosomes and chromosome arms, although a cause and effect relationship between aneuploidy and cancer has not been established.
Evolution
Comparative genomics studies of mammalian genomes suggest that approximately 5% of the human genome has been conserved by evolution since the divergence of those species approximately 200 million years ago, containing the vast majority of genes and regulatory sequences. Intriguingly, since genes and known regulatory sequences probably comprise less than 2% of the genome, this suggests that there may be more unknown functional sequence than known functional sequence. A smaller, but large, fraction of human genes seem to be shared among most known vertebrates.
The chimpanzee genome is approximately 95% identical to the human genome. On average, a typical human protein-coding gene differs from its chimpanzee ortholog by only two amino acid substitutions; nearly one third of human genes are exactly identical to their chimpanzee orthologs. See: Chimpanzee Genome Project.
Humans have undergone an extraordinary loss of olfactory receptor genes during our recent evolution, which explains our relatively crude sense of smell compared to most other mammals. Evolutionary evidence suggests that the emergence of color vision in humans and several other primate species has diminished the need for the sense of smell.
Mitochondrial genome
The human mitochondrial genome, while usually not included when referring to the "human genome", is of tremendous interest to geneticists, since it undoubtedly plays a role in mitochondrial disease. It also sheds light on human evolution; for example, analysis of variation in the human mitochondrial genome has led to the postulation of a Mitochondrial Eve from whom all modern humans are descended.
References
Gilad, Y., et. al. "Loss of olfactory receptor genes coincides with the acquisition of full trichromatic vision in primates." PLoS Biology 2(1):e5, January 2004.
International Human Genome Sequencing Consortium. "Initial sequencing and analysis of the human genome" Nature 409:860-921, February 2001.
International Human Genome Sequencing Consortium. "Finishing the euchromatic sequence of the human genome" Nature 431:931-945, October 2004.
Mouse Genome Sequencing Consortium. "Initial sequencing and comparative analysis of the mouse genome" Nature 420:520-562, December 2002.
Olson, M.V., and Varki, A. "Sequencing the chimpanzee genome: insights into human evolution and disease" Nature Reviews Genetics 4:20-28, January 2003.
The Chimpanzee Sequencing and Analysis Consortium. "Initial sequence of the chimpanzee genome and comparison with the human genome" Nature 437:69-87, September 2005.
See also
External Links
- The National Human Genome Research Institute [1]
- National Library of Medicine human genome viewer [2].
- UCSC Genome Browser [3].
- Human Genome Project [4].
Categories: Genetics | Genomics | Humans
