Download __TOP__ The Human Genome
Fernande Westmoreland
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.[2] Human genomes include both protein-coding DNA sequences and various types of DNA that does not encode proteins. The latter is a diverse category that includes DNA coding for non-translated RNA, such as that for ribosomal RNA, transfer RNA, ribozymes, small nuclear RNAs, and several types of regulatory RNAs. It also includes promoters and their associated gene-regulatory elements, DNA playing structural and replicatory roles, such as scaffolding regions, telomeres, centromeres, and origins of replication, plus large numbers of transposable elements, inserted viral DNA, non-functional pseudogenes and simple, highly repetitive sequences. Introns make up a large percentage of non-coding DNA. Some of this non-coding DNA is non-functional junk DNA, such as pseudogenes, but there is no firm consensus on the total amount of junk 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) consist of 3,054,815,472 DNA base pairs (if X chromosome is used),[3] while female 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[4] and 0.6% when considering indels),[5] these are considerably smaller than the differences between humans and their closest living relatives, the bonobos and chimpanzees (1.1% fixed single-nucleotide variants[6] and 4% when including indels).[7] Size in base pairs can vary too; the telomere length decreases after every round of DNA replication.
Although the sequence of the human genome has been completely determined by DNA sequencing in 2022 (including methylation),[3] it is not yet fully understood. Most, but 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 (in particular, annotation of the complete CHM13v2.0 sequence is still ongoing[8]). And yet, overlapping genes are quite common, in some cases allowing two protein coding genes from each strand to reuse base pairs twice (for example, genes DCDC2 and KAAG1).[9] 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.[citation needed] There are also a significant number of retroviruses in human DNA, at least 3 of which have been proven to possess an important function (i.e., HIV-like HERV-K, HERV-W, and HERV-FRD play a role in placenta formation by inducing cell-cell fusion).
In 2003, scientists reported the sequencing of 85% of the entire human genome, but as of 2020 at least 8% was still missing.[citation needed] In 2021, scientists reported sequencing the complete female genome (i.e., without the Y chromosome).[10] This sequence identified 19,969 protein-coding sequences, accounting for approximately 1.5% of the genome, and 63,494 genes in total, most of them being non-coding RNA genes.[3] The genome consists of regulatory DNA sequences, LINEs, SINEs, introns, and sequences for which as yet no function has been determined. The human Y chromosome, consisting of 62,460,029 base pairs from a different cell line and found in all males, was sequenced completely in January 2022.[11][12]
In 2023, a draft human pangenome reference was published.[13] It is based on 47 genomes from persons of varied ethnicity.[13] Plans are underway for an improved reference capturing still more biodiversity from a still wider sample.[13]
The first human genome sequences were published in nearly complete draft form in February 2001 by the Human Genome Project[14] and Celera Corporation.[15] 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.[16] 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.[17]
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.[citation needed]
In 2022 the Telomere-to-Telomere (T2T) consortium reported the complete sequence of a human female genome,[3] filling all the gaps in the X chromosome (2020) and the 22 autosomes (May 2021).[3][25] The previously unsequenced parts contain immune response genes that help to adapt to and survive infections, as well as genes that are important for predicting drug response.[26] The completed human genome sequence will also provide better understanding of human formation as an individual organism and how humans vary both between each other and other species.[26]
The total length of the human reference genome does not represent the sequence of any specific individual. 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. The haploid genome is 3 054 815 472 base pairs, when the X chromosome is included, and 2 963 015 935 base pairs when the Y chromosome is substituted for the X chromosome. These chromosomes 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 mitochondrion.
Variations are unique DNA sequence differences that have been identified in the individual human genome sequences analyzed by Ensembl as of December 2016. The number of identified variations is expected to increase as further personal genomes are sequenced and analyzed. In addition to the gene content shown in this table, a large number of non-expressed functional sequences have been identified throughout the human genome (see below). Links open windows to the reference chromosome sequences in the EBI genome browser.
The haploid human genome (23 chromosomes) is about 3 billion base pairs long and in 2018 was said to contain at least 46,831 genes. In 2022 the number increased again to 63,494 genes. The increase from the previously accepted number of around 20,000 is due to the difficulty of defining what a gene is. It is widely agreed that there are about 20,000 protein-coding genes, with some papers stating exact figures of 21,306. The higher figures include non-protein coding RNA-producing genes that perform other cell functions.[40][41][42][43]
Since every base pair can be coded by 2 bits, this is about 750 megabytes of data. An individual somatic (diploid) cell contains twice this amount, that is, about 6 billion base pairs. Males have fewer than females because the Y chromosome is about 62 million base pairs whereas the X is about 154 million. Since individual genomes vary in sequence by less than 1% from each other, the variations of a given human's genome from a common reference can be losslessly compressed to roughly 4 megabytes.[44]
The entropy rate of the genome differs significantly between coding and non-coding sequences. It is close to the maximum of 2 bits per base pair for the coding sequences (about 45 million base pairs), but less for the non-coding parts. It ranges between 1.5 and 1.9 bits per base pair for the individual chromosome, except for the Y chromosome, which has an entropy rate below 0.9 bits per base pair.[45]
The content of the human genome is commonly divided into coding and noncoding DNA sequences. Coding DNA is defined as those sequences that can be transcribed into mRNA and translated into proteins during the human life cycle; these sequences occupy only a small fraction of the genome (
Some noncoding DNA contains genes for RNA molecules with important biological functions (noncoding RNA, for example ribosomal RNA and transfer RNA). The exploration of the function and evolutionary origin of noncoding DNA is an important goal of contemporary genome research, including the ENCODE (Encyclopedia of DNA Elements) project, which aims to survey the entire human genome, using a variety of experimental tools whose results are indicative of molecular activity. It is however disputed whether molecular activity (transcription of DNA into RNA) alone implies that the RNA produced has a meaningful biological function, since experiments have shown that random nonfunctional DNA will also reproducibly recruit transcription factors resulting in transcription into nonfunctional RNA.[46]
There is no consensus on what constitutes a "functional" element in the genome since geneticists, evolutionary biologists, and molecular biologists employ different definitions and methods.[47][48] Due to the ambiguity in the terminology, different schools of thought have emerged.[49] In evolutionary definitions, "functional" DNA, whether it is coding or non-coding, contributes to the fitness of the organism, and therefore is maintained by negative evolutionary pressure whereas "non-functional" DNA has no benefit to the organism and therefore is under neutral selective pressure. This type of DNA has been described as junk DNA[50][51] In genetic definitions, "functional" DNA is related to how DNA segments manifest by phenotype and "nonfunctional" is related to loss-of-function effects on the organism.[47] In biochemical definitions, "functional" DNA relates to DNA sequences that specify molecular products (e.g. noncoding RNAs) and biochemical activities with mechanistic roles in gene or genome regulation (i.e. DNA sequences that impact cellular level activity such as cell type, condition, and molecular processes).[52][47] There is no consensus in the literature on the amount of functional DNA since, depending on how "function" is understood, ranges have been estimated from up to 90% of the human genome is likely nonfunctional DNA (junk DNA)[53] to up to 80% of the genome is likely functional.[54] It is also possible that junk DNA may acquire a function in the future and therefore may play a role in evolution,[55] but this is likely to occur only very rarely.[50] Finally DNA that is deliterious to the organism and is under negative selective pressure is called garbage DNA.[51]
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