Human genome

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 biomedical sciences.

Chromosomes
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. Somatic cells usually have 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
There are an estimated 20,000-25,000 human protein-coding genes. 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.

Surprisingly, the number of human genes seems to be within a factor of two of many 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 thought to be much larger than those of the aforementioned organisms.

Most human genes have multiple exons, and human introns are frequently much longer than the flanking exons.

Human genes are distributed unevenly across the chromosomes. Each chromosome contains various 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, miRNA, 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 sequences (specifically exons) comprise less than 1.5% of the human genome. Aside from genes and known regulatory sequences, the human genome contains vast regions of DNA the function of which, if any, remains unknown. These regions in fact comprise the vast majority, by some estimates 97%, of the human genome size. Much of this is comprised of repeat elements, transposons, and pseudogenes, but there is also a large amount of sequence that does not fall under any known classification.

Most of this sequence is probably an evolutionary artifact that serves no present-day purpose, and these regions are sometimes collectively referred to as "junk" DNA. However, there are a variety of emerging indications that some sequences within may function in ways that are not currently understood. Recent experiments using microarrays have revealed that a large fraction of "noncoding" DNA is in fact transcribed into RNA, which leads to the possibility that the resulting transcripts may have some unknown function. Also, the apparent evolutionary conservation across the mammalian genomes of much more sequence than can be explained by protein-coding regions suggests that a large amount of noncoding DNA may have an important function. The investigation of possible roles for noncoding DNA, such as the regulation of protein expression or organism development, is currently a major avenue of scientific inquiry in human genomics.

Variation
Most studies of human genetic variation have focused on single nucleotide polymorphisms (SNPs), which are substitutions in individual bases along a chromosome. 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 and DNA paternity testing. 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 have exactly the same protein translation as their chimpanzee orthologs. A major difference between the two genomes is human chromosome 2, which is the product of a fusion between chimpanzee chromosomes 12 and 13.

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.