The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria.
These are usually treated separately as the nuclear genome and the mitochondrial genome.
Human genomes include both protein-coding DNA genes and noncoding DNA. Haploid human genomes, which are contained in germ cells, the egg and sperm gamete cells created in the meiosis phase of sexual reproduction before fertilization creates a zygote, consist of three billion DNA base pairs, while diploid genomes (found in somatic cells) have twice the DNA content.
While there are significant differences among the genomes of human individuals (on the order of 0.1% due to single-nucleotide variants and 0.6% when considering indels), these are considerably smaller than the differences between humans and their closest living relatives, the bonobos and chimpanzees (~1.1% fixed single-nucleotide variants and 4% when including indels).
Although the sequence of the human genome has been (almost) completely determined by DNA sequencing, it is not yet fully understood. Most (though probably not all) genes have been identified by a combination of high throughput experimental and bioinformatics approaches, yet much work still needs to be done to further elucidate the biological functions of their protein and RNA products.
More information: National Human Genome Research Institute
Recent results suggest that most of the vast quantities of noncoding DNA within the genome have associated biochemical activities, including regulation of gene expression, organization of chromosome architecture, and signals controlling epigenetic inheritance.
Prior to the acquisition of the full genome sequence, estimates of the number of human genes ranged from 50,000 to 140,000, with occasional vagueness about whether these estimates included non-protein coding genes.
As genome sequence quality and the methods for identifying protein-coding genes improved, the count of recognized protein-coding genes dropped to 19,000-20,000. However, a fuller understanding of the role played by sequences that do not encode proteins, but instead express regulatory RNA, has raised the total number of genes to at least 46,831, plus another 2300 micro-RNA genes. By 2012, functional DNA elements that encode neither RNA nor proteins have been noted and another 10% equivalent of human genome was found in a recent (2018) population survey.
Protein-coding sequences account for only a very small fraction of the genome (approximately 1.5%), and the rest is associated with non-coding RNA genes, regulatory DNA sequences, LINEs, SINEs, introns, and sequences for which as yet no function has been determined.
The first human genome sequences were published in nearly complete draft form in February 2001 by the Human Genome Project and Celera Corporation.
More information: Human Genome Project Information Archive
Completion of the Human Genome Project's sequencing effort was announced in 2004 with the publication of a draft genome sequence, leaving just 341 gaps in the sequence, representing highly-repetitive and other DNA that could not be sequenced with the technology available at the time.
The human genome was the first of all vertebrates to be sequenced to such near-completion, and as of 2018, the diploid genomes of over a million individual humans had been determined using next-generation sequencing. These data are used worldwide in biomedical science, anthropology, forensics and other branches of science. Such genomic studies have led to advances in the diagnosis and treatment of diseases, and to new insights in many fields of biology, including human evolution.
In June 2016, scientists formally announced HGP-Write, a plan to synthesize the human genome.
Although the 'completion' of the human genome project was announced in 2001, there remained hundreds of gaps, with about 5–10% of the total sequence remaining undetermined. The missing genetic information was mostly in repetitive heterochromatic regions and near the centromeres and telomeres, but also some gene-encoding euchromatic regions. There remained 160 euchromatic gaps in 2015 when the sequences spanning another 50 formerly-unsequenced regions were determined.
Only in 2020 was the first truly complete telomere-to-telomere sequence of a human chromosome determined, namely of the X chromosome.
The total length of the human reference genome, that does not represent the sequence of any specific individual, is over 3 billion base pairs.
The genome is organized into 22 paired chromosomes, termed autosomes, plus the 23rd pair of sex chromosomes (XX) in the female, and (XY) in the male.
These are all large linear DNA molecules contained within the cell nucleus. The genome also includes the mitochondrial DNA, a comparatively small circular molecule present in multiple copies in each of the mitochondrion.
More information: Nature
contain deserts, or large, gene-poor regions.
Craig Venter
