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Human genome

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The human genome is the total genetic information (DNA content) in human cells. It really comprises two genomes: a complex nuclear genome with about 20,000 to 25,000 genes, and a much smaller mitochondrial genome with 37 genes. The nuclear genome provides the great bulk of essential genetic information, most of which specifies polypeptide synthesis on cytoplasmic ribosomes.

Mitochondria possess their own ribosomes and the very few polypeptide-encoding genes in the mitochondrial genome produce mRNAs which are translated on the mitochondrial ribosomes. However, the mitochondrial genome specifies only a very small portion of the specific mitochondrial functions; the bulk of the mitochondrial polypeptides are encoded by nuclear genes and are synthesized on cytopladmic ribosomes, before being imported into the mitochondria.

Human-mouse comparisons have shown that less than 5% of the genome is very similar, including the 1.5% devoted to coding DNA and a somewhat higher percentage including similar sequences within untranslated sequences, regulatory elements and so on.[1][2] The majority of the coding DNA is used to make mRNA and hence polypeptides but a significant minority (at least 5% and probably close to 10%) of the human genes specifies noncoding (=untranslated) RNA (RNA genes). A variety of novel RNA genes have recently been identified, forcing reassessment of RNA function.

The coding sequences frequently belong to families of related sequences, DNA sequence families, which may be organized into clusters on one or more chromosomes or be dispersed. Sequencing of the genome provided the first genome-wide assessment of duplication, and revealed a very significant amount of primate-specific segmental duplication; very closely related blocks of sequences are found on different chromosomes or in different regions of a single chromosome.[3]

The mechanisms giving rise to duplicated genes also give rise to nonfunctional gene-related sequences, including pseudogenes and gene fragments. There are numerous defective copies of RNA genes scattered through the genome, and for some polypeptide-encoding genes, too, many related pseudogenes are also found: analyses of the finished chromosome 21 and 22 sequences predicts a total of about 20,000 pseudogenes in the genome.[4][5]

As in other complex genomes, a very large component of the human genome is made up of noncoding DNA. A sizeable component is organized in tandem head to tail repeats, but the majority consists of interspersed repeats which have originated from RNA transcripts by retrotransposition, (cellular reverse transcriptases can copy RNA transcripts to make natural CDNA which can integrate elsewhere in the genome).

Human mitochondrial genome

The human mitochondrial genome is defined by a single type of circular double-stranded DNA whose complete nucleotide sequence has been established.[6][7] It is 16,569 bp in length and is 44% (G+C). The two DNA strands have significantly different base compositions: the heavy strand is rich in guanines, the light strand is rich in cytosines. Although the mitochondrial DNA is principally double stranded, a small section shows a triple DNA strand structure due to the repetitive synthesis of a short segment of heavy strand DNA, 7S DNA. Human cells typically contain thousands of copies of the double-stranded mitochondrial DNA molecule, but the number can vary considerably in different cell types.

During zygote (fertilised egg) formation, a sperm cell contributes its nuclear genome, but not its mitochondrial genome, to the egg cell. Consequently, the mitochondrial genome of the zygote is usually determined exclusively by that originally found in the unfertilized egg. The mitochondrial genome is therefore maternally inherited: males and females both inherit their mitochondria from their mother but males do not transmit their mitochondria to subsequent generations. Thus mitochondrially encoded genes or DNA variants give a specific pedigree pattern. During mitotic cell division, the mitochondrial DNA molecules of the dividing cell segregate in a purely random way to the two daughter cells.

The human mitochondrial genome contains 37 genes. For 28 of the genes the heavy strand is the sense strand; for the other nine, the light strand is the sense strand. Of the 37 genes, a total of 24 specify a mature RNA product: 22 mitochondrial tRNA molecules and two mitochondrial rRNA molecules, a 23S rRNA and a 16S rRNA. The remaining 13 genes encode polypeptides which are synthesized on mitochondrial ribosomes.

Each of the 13 polypeptides, encoded by the mitochondrial genome is a subunit of one of the mitochondrial respiratory complexes, the multichain enzymes of oxidative phosphorylation which are engaged in the production of ATP. There is, however, a total of about 100 different polypeptide subunits in the mitochondrial oxidative phosphorylation system, and so the vast majority are encoded by nuclear genes. All other mitochondrial proteins are encoded by the nuclear genome and are translated on cytoplasmic ribosomes before being imported into the mitochondria.

The mitochondrial genetic code is used to decode the heavy and light chain transcripts to give a total of only 13 polypeptides. This very small functional load has allowed the mitochondrial genetic code to differ from the universal genetic code (which needs to cater for 30,000 or so genes). There are 60 mitochondrial sense codons, one fewer than in the nuclear genetic code, and four stop codons. Two of the four stop codons, UAA and UAG, also serve as stop codons in the nuclear genetic code, but the other two are AGA and AGG which specify arginine in the nuclear genetic code. UGA encodes tryptophan rather than serving as a stop codon and AUA specifies methionine not isoleucine.

The mitochondrial genome encodes all the rRNA and tRNA molecules it needs for synthesizing proteins but relies on nuclear-encoded genes to provide all other components (such as the protein components of mitochondrial ribosomes, amino acyl tRNA synthetases etc.). As there are only 22 different types of human mitochondrial tRNA, individual tRNA molecules need to be able to interpret several different codons. This is possible because of third base wobble in codon interpretation. Eight of the 22 tRNA molecules have anticodons which are each able to recognize families of four codons differing only at the third base, and 14 recognize pairs of codons which are identical at the first two base positions and share either a purine or a pyrimidine at the third base. Between them, therefore, the 22 mitochondrial tRNA molecules can recognize a total of 60 codons [(8 X 4) + (14 X 2)].

In addition to their differences in genetic capacity and different genetic codes, the mitochondrial and nuclear genomes differ in many other aspects of their organization and expression.


  1. Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature, 2002, 420, 520-562.
  2. Dermitzakis, E.T.; Reymond, A.; Lyle, R.: et al. Numerous potentially functional but non-genic conserved sequences on human chromosome 21. Nature, 2002, 420, 578-582.
  3. Bailey, J.A.; Gu, Z.; Clark, R.A. et al. Recent segmental duplications in the human genome. Science, 2002, 297, 1003-1007.
  4. Harrison, P.M.: Hegyi, H.; Balasubramanian, S.: et al. Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22. Genome Res. 2002, 12, 272-280.
  5. Collins, J.E.; Goward, M.E.; Cole, C.G.; et al. Reevaluating human gene annotation: a second generation analysis of chromosome 22. Genome Res. 2003, 13, 27-36
  6. Anderson, S.; Bankier, A.T.; Barrell, B.G.; et al. Sequence and organization of the human mitochondrial genome. Nature, 1981, 290, 457-465.
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