PR domain[note 1] zinc finger protein 9 is a
protein that in humans is encoded by the PRDM9gene.[5] PRDM9 is responsible for positioning
recombination hotspots during
meiosis by binding a DNA sequence motif encoded in its zinc finger domain.[6] PRDM9 is the only
speciation gene found so far in mammals, and is one of the fastest evolving genes in the genome.[7][8]
Domain Architecture
Schematic of the PRDM9 Domain Architecture in mice
In 1974 Jiri Forejt and P. Ivanyi identified a locus which they named Hst1 which controlled hybrid sterility.[10]
In 1982 a haplotype was identified controlling recombination rate wm7,[11] which would later be identified as PRDM9.[12]
In 1991 a protein binding to the minisatelite consensus sequence 5′-CCACCTGCCCACCTCT-3′ was detected and partially purified (named Msbp3 - minisatelite binding protein 3).[13] This would later turn out to be the same PRDM9 protein independently identified later.[14]
In 2005 a gene was identified (named Meisetz) that is required for progression through meiotic prophase and has H3K4 methyltransferase activity.[15]
In 2009 Jiri Forejt and colleagues identified Hst1 as Meisetz/PRDM9 - the first and so far only speciation gene in mammals.[16]
Later in 2009 PRDM9 was identified as one of the fastest evolving genes in the genome.[9][17]
In 2010 three groups independently identified PRDM9 as controlling the positioning of recombination hotspots in humans and mice.[6][18][19][20][21]
in 2012 it was shown that almost all hotspots are positioned by PRDM9 and that in its absence hotspots form near promoters.[22]
In 2014 it was reported that the PRDM9 SET domain could also trimethylate H3K36 in vitro,[23] which was confirmed in vivo in 2016.[24]
In 2016 it was shown that the hybrid sterility caused by PRDM9 can be reversed and that the sterility is caused by asymmetric double strand breaks.[25][26]
Function in Recombination
PRDM9 mediates the process of meiosis by directing the sites of homologous recombination.[27] In humans and mice, recombination does not occur evenly throughout the genome but at particular sites along the chromosomes called
recombination hotspots. Hotspots are regions of DNA about
1-2kb in length.[28] There are approximately 30,000 to 50,000 hotspots within the human
genome corresponding to one for every 50-100kb DNA on average.[28] In humans, the average number of crossover recombination events per hotspot is one per 1,300
meioses, and the most extreme hotspot has a crossover frequency of one per 110 meioses.[28] These hotspots are binding sites for the PRDM9 Zinc Finger array.[29] Upon binding to DNA, PRDM9 catalyzes trimethylation of Histone 3 at lysine 4 and lysine 36.[30] As a result, local nucleosomes are reorganized and through an unknown mechanism the recombination machinery is recruited to form double strand breaks.
^Ponting CP (May 2011). "What are the genomic drivers of the rapid evolution of PRDM9?". Trends in Genetics. 27 (5): 165–71.
doi:
10.1016/j.tig.2011.02.001.
PMID21388701.
^
abcMyers S, Spencer CC, Auton A, Bottolo L, Freeman C, Donnelly P, McVean G (August 2006). "The distribution and causes of meiotic recombination in the human genome". Biochemical Society Transactions. 34 (Pt 4): 526–30.
doi:
10.1042/BST0340526.
PMID16856851.
Jiang GL, Huang S (January 2000). "The yin-yang of PR-domain family genes in tumorigenesis". Histology and Histopathology. 15 (1): 109–17.
PMID10668202.
PR domain[note 1] zinc finger protein 9 is a
protein that in humans is encoded by the PRDM9gene.[5] PRDM9 is responsible for positioning
recombination hotspots during
meiosis by binding a DNA sequence motif encoded in its zinc finger domain.[6] PRDM9 is the only
speciation gene found so far in mammals, and is one of the fastest evolving genes in the genome.[7][8]
Domain Architecture
Schematic of the PRDM9 Domain Architecture in mice
In 1974 Jiri Forejt and P. Ivanyi identified a locus which they named Hst1 which controlled hybrid sterility.[10]
In 1982 a haplotype was identified controlling recombination rate wm7,[11] which would later be identified as PRDM9.[12]
In 1991 a protein binding to the minisatelite consensus sequence 5′-CCACCTGCCCACCTCT-3′ was detected and partially purified (named Msbp3 - minisatelite binding protein 3).[13] This would later turn out to be the same PRDM9 protein independently identified later.[14]
In 2005 a gene was identified (named Meisetz) that is required for progression through meiotic prophase and has H3K4 methyltransferase activity.[15]
In 2009 Jiri Forejt and colleagues identified Hst1 as Meisetz/PRDM9 - the first and so far only speciation gene in mammals.[16]
Later in 2009 PRDM9 was identified as one of the fastest evolving genes in the genome.[9][17]
In 2010 three groups independently identified PRDM9 as controlling the positioning of recombination hotspots in humans and mice.[6][18][19][20][21]
in 2012 it was shown that almost all hotspots are positioned by PRDM9 and that in its absence hotspots form near promoters.[22]
In 2014 it was reported that the PRDM9 SET domain could also trimethylate H3K36 in vitro,[23] which was confirmed in vivo in 2016.[24]
In 2016 it was shown that the hybrid sterility caused by PRDM9 can be reversed and that the sterility is caused by asymmetric double strand breaks.[25][26]
Function in Recombination
PRDM9 mediates the process of meiosis by directing the sites of homologous recombination.[27] In humans and mice, recombination does not occur evenly throughout the genome but at particular sites along the chromosomes called
recombination hotspots. Hotspots are regions of DNA about
1-2kb in length.[28] There are approximately 30,000 to 50,000 hotspots within the human
genome corresponding to one for every 50-100kb DNA on average.[28] In humans, the average number of crossover recombination events per hotspot is one per 1,300
meioses, and the most extreme hotspot has a crossover frequency of one per 110 meioses.[28] These hotspots are binding sites for the PRDM9 Zinc Finger array.[29] Upon binding to DNA, PRDM9 catalyzes trimethylation of Histone 3 at lysine 4 and lysine 36.[30] As a result, local nucleosomes are reorganized and through an unknown mechanism the recombination machinery is recruited to form double strand breaks.
^Ponting CP (May 2011). "What are the genomic drivers of the rapid evolution of PRDM9?". Trends in Genetics. 27 (5): 165–71.
doi:
10.1016/j.tig.2011.02.001.
PMID21388701.
^
abcMyers S, Spencer CC, Auton A, Bottolo L, Freeman C, Donnelly P, McVean G (August 2006). "The distribution and causes of meiotic recombination in the human genome". Biochemical Society Transactions. 34 (Pt 4): 526–30.
doi:
10.1042/BST0340526.
PMID16856851.
Jiang GL, Huang S (January 2000). "The yin-yang of PR-domain family genes in tumorigenesis". Histology and Histopathology. 15 (1): 109–17.
PMID10668202.