Pseudoautosomal region

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Excerpt from a human metaphase spread. A region in the pseudoautosomal region on the short arms of the X chromosome (left) and the Y chromosome (top right) was detected with fluorescence in situ hybridization (green colons, one point per chromatid ). Chromosomes are shown in red.
human X chromosome
human Y chromosome

Pseudoautosomal regions (PAR) are sections in the genome of some living organisms that have homologous DNA sequences on different sex chromosomes of the corresponding species . In mammals, they are on the X and Y chromosomes, respectively. PAR are equally often present in both sexes, as is otherwise the case with autosomes , hence the name. The PAR enables the pairing of the otherwise different sex chromosomes during meiosis . A recombination takes place in the area of ​​the PAR through crossing-over .

Mammalian pseudo-autosomal regions

There are two PARs on the mammalian sex chromosomes:

  • In humans, PAR1 is 2.7 million base pairs (Mb) in size, is located at the end of the short arm (the so-called p-arm) of the sex chromosomes and is also called p-PAR. A mandatory crossing-over takes place here during meiosis in male individuals .
  • In humans, PAR2 is 0.33 Mb, is located at the end of the long arm (q-arm) of the sex chromosomes and is also called q-PAR. A crossing-over during meiosis in male individuals is not mandatory and is even relatively rare.

So far, a total of around 30 genes have been identified in the area of ​​the two PARs.

The investigation of the PAR in the Y chromosome of horses (ECAY: E quus ca ballus Y chromosome) was helpful in the production of the first genome maps of the so-called euchromatic regions of ECAY. Such studies are animal medical terms for the study of male fertility ( fertility ) of horses and therefore also important for breeding matters. In numerous investigations into so-called quantitative trait loci , the PAR are also included in the search. For example, markers for susceptibility (vulnerability markers ) to BSE , markers for behavior and body structure of cattle, or resistance to pathogens are sought.

In addition to the PAR, there can also be other homologous regions on sex chromosomes in which the sequences are similar (and thus have a common origin), but are not (no longer) identical. In humans these are Xq21.3 and Yp11.1.

Genetic characteristics

It is known for PAR1 that recombinations occur there much more frequently than in other areas of the genome . The frequency of recombinations increases the further the affected gene segments are in the direction of the chromosome ends , i.e. the telomeres . The extent of the recombination frequency seems to differ significantly in different species. Since it is assumed that gene sections that are often affected by recombinations are also frequently affected by mutations , the PARs were examined for mutation frequency. At least in the case of humans and other primates , the PAR are affected by mutations much less often than expected.

As far as the accumulation of recombinations within PAR1 is concerned, there is a notable difference between the ratios in humans and mice , which is referred to as the "PAR-Boundary Paradox". If one examines the gene region in humans that separates the PAR1 from the gene segments further to the center, i.e. towards the centromere , it becomes apparent that the recombination frequency within the PAR1 is 20 times higher than in the rest of the genome. At the same time, there are above-average numbers of GC sections. The accumulation of GC-rich sequences in PAR1 is interpreted as an evolutionary consequence of the accumulated recombinations in these gene segments. In mice, on the other hand, there is no positive correlation between recombination rates and GC content in this chromosome segment.

Genes in PAR1 and PAR2 in the human genome

The following genes are found in the pseudoautosomal regions in humans: ASMT, ASMTL, CD99, CRLF2, CSF2RA, SFRS17A, DHRSXY, GTPBP6, IL3RA, P2RY8, PLCXD1, PPP2R3B, SHOX, SLC25A9, SYBL1, SPRY3, XG, ILBED1, SPRY3.

Human diseases associated with PAR

Amelogenesis imperfecta.

In humans, there is a hereditary disease that is associated with short stature and a deformation of the spoke ( Madelung deformity ), the so-called dyschondrosteosis Léri Weill (LWD). This disease is a pseudoautosomal dominant disease. This means that the genes that are responsible for the disease are located in the pseudoautosomal region of the sex chromosomes and that inheritance is dominant. In Léri-Weill dyschondrosteosis (LWD) there are deletions in the area of ​​PAR1. The SHOX gene involved in this disease is probably also involved in other genetic diseases (the so-called "Langer mesomelic dysplasia" and Turner syndrome ). PAR deletions in men are associated with infertility , which is due to azoospermia (lack of sperm in the ejaculate). The so-called R * Y elements are a specialty. These are DNA sequences that form a triple helix. These "triplexes" prevent the transcription and replication of DNA and increase the likelihood of genetic rearrangements. On the sex chromosomes, these sequences are used to switch off genes. They are often found in the introns of genes that are expressed in the brain and that may play a role in the development of mental illness. Since these gene segments are found in the vicinity of rapidly mutating genes, it is assumed that they play a role in the evolution of the genome. Defects in the amelogenin gene in PAR1 cause a disorder of tooth enamel formation called amelogenesis imperfecta .

PAR in plants

White carnation ( Silene latifolia ).

The PAR has also been studied in plants. Studies on meiosis in the carnation species white light carnation ( Silene latifolia ) have shown that the recombination does not take place between the two long arms of the sex chromosomes, but between the short arm of the X chromosome and the long arm of the Y chromosome. Since the sex chromosomes in this species are very young (they were only formed about 10–20 million years ago), the study of the PAR of the white carnation is particularly informative. Detailed investigations of this PAR support the old hypothesis that the sex chromosomes arose from a pair of autosomes.

Evolutionary Aspects

Derby Wallaby

PAR2 on the Y chromosome contains four genes and was believed to have been duplicated during mammalian development . Investigations into the position of the PAR2 genes in lemurs , cats and the derby wallaby have shown that the mutations responsible for them occurred 70 to 130 million years ago and 60 to 70 million years ago. The border between PAR2 and the other sections on the X and Y chromosomes also does not seem to be very sharp, since the amelogenin gene straddles this border in mammals. This observation is interpreted in such a way that the evolution of the sex chromosomes, which began in mammals about 300 million years ago, has to do with changes in the genes ( SRY ) that determine the male phenotype.

The Y chromosome

In humans, the Y chromosome is around 65 Mb and contains around 78 active genes. The Y-chromosome of the narrow-foot pouch mice is even smaller at approx. 10 Mb. It does not contain PAR, but the SRY gene is also found on it . This finding supports the assumption that there is a common ancestor of the Y chromosome at least in the case of the marsupial mammals Marsupialia and the higher mammals Eutheria .

The autosomal origin of the X chromosome

platypus

It has long been suspected that the sex chromosomes of mammals evolved from autosomal regions. Genetic studies have shown that the long arm of the X chromosome is common in all mammals. The first indications of a successive process of the formation of the X chromosome were found when comparing gene regions on the short X arm: in platypus and marsupial (Marsupialia) sections are missing that are present in the human X chromosome. This implies that the entire short X arm recently became part of the X chromosome in the higher mammals, Eutheria .

All three mammalian subclasses ( higher mammals , marsupials, and mammals ) have matching regions of the X chromosome, but marsupials (Marsupialia) and monotremes have an autosomal region in common, which is located on the X chromosome in the higher mammals. This suggests that at least parts of the X chromosome were originally an autosome chromosome. The same applies to the Y chromosome, only that there the proportion of genetic material that probably comes from autosomes is much more extensive.

The age of the sex chromosomes

The investigation of the chromosomal localization of the amelogenin gene (AMG) in derby wallaby (Marsupialia), platypus (Monotremata) and humans (Eutheria) also suggests an autosomal origin of the short X arm . In wallabies and platypus, AMG sits on the autosomes 5q and 1q as well as 1 and 2 and in humans on Xp22 and Yp11 (i.e. in PAR1). Based on the assumption that the radiation of mammals from a common ancestor took place about 150 million years ago, one concludes that AMG was added to the PAR 80 to 150 million years ago and that the X and Y chromosomes are at least as old.

See also

Individual evidence

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