scholarly journals A Game of Thrones at Human Centromeres I. Multifarious structure necessitates a new molecular/evolutionary model

2019 ◽  
Author(s):  
William R. Rice
Keyword(s):  
Spatial Organization ◽  
Repeat Unit ◽  
Rapid Evolution ◽  
Evolutionary Model ◽  
Generic Model ◽  
Crossing Over ◽  
Unequal Crossing Over ◽  
Centromeric Repeat ◽  
Repeat Units ◽  
Protein Binding Sequence

Human centromeres form over arrays of tandemly repeated DNA that are exceptionally complex (repeats of repeats) and long (spanning up to 8 Mbp). They also have an exceptionally rapid rate of evolution. The generally accepted model for the expansion/contraction, homogenization and evolution of human centromeric repeat arrays is a generic model for the evolution of satellite DNA that is based on unequal crossing over between sister chromatids. This selectively neutral model predicts that the sequences of centromeric repeat units will be effectively random and lack functional constraint. Here I used shotgun PacBio SMRT reads from a homozygous human fetal genome (female) to determine and compare the consensus sequences (and levels of intra-array variation) for the active centromeric repeats of all the chromosomes. To include the Y chromosome using the same technology, I used the same type of reads from a diploid male. I found many different forms and levels of conserved structure that are not predicted by –and sometimes contradictory to– the unequal crossing over model. Much of this structure is based on spatial organization of three types of ~170 bp monomeric repeat units that are predicted to influence centromere strength (i.e., the level of outer kinetochore proteins): one with a protein-binding sequence at its 5’ end (a 17 bp b-box that binds CENP-B), a second that is identical to the first except that the b-box is mutated so that it no longer binds CENP-B, and a third lacking a b-box but containing a 19 bp conserved “n-box” sequence near its 5’ end. The frequency and organization of these monomer types change markedly as the number of monomers per repeat unit increases, and also differs between inactive and active arrays. Active arrays are also much longer than flanking, inactive arrays, and far longer than required for cellular functioning. The diverse forms of structure motivate a new hypothesis for the lifecycle of human centromeric sequences. These multifarious levels of structures, and other lines of evidence, collectively indicate that a new model is needed to explain the form, function, expansion/contraction, homogenization and rapid evolution of centromeric sequences.

Structure, organization, and sequence of alpha satellite DNA from human chromosome 17: evidence for evolution by unequal crossing-over and an ancestral pentamer repeat shared with the human X chromosome

1986 ◽  
Vol 6 (9) ◽  
pp. 3156-3165
Author(s):  
J S Waye ◽  
H F Willard
Keyword(s):  
Human Chromosome ◽  
X Chromosome ◽  
Repeat Unit ◽  
Higher Order ◽  
Chromosome 17 ◽  
Crossing Over ◽  
Human Chromosomes ◽  
Alpha Satellite ◽  
Unequal Crossing Over ◽  
Human Chromosome 17

The centromeric regions of all human chromosomes are characterized by distinct subsets of a diverse tandemly repeated DNA family, alpha satellite. On human chromosome 17, the predominant form of alpha satellite is a 2.7-kilobase-pair higher-order repeat unit consisting of 16 alphoid monomers. We present the complete nucleotide sequence of the 16-monomer repeat, which is present in 500 to 1,000 copies per chromosome 17, as well as that of a less abundant 15-monomer repeat, also from chromosome 17. These repeat units were approximately 98% identical in sequence, differing by the exclusion of precisely 1 monomer from the 15-monomer repeat. Homologous unequal crossing-over is suggested as a probable mechanism by which the different repeat lengths on chromosome 17 were generated, and the putative site of such a recombination event is identified. The monomer organization of the chromosome 17 higher-order repeat unit is based, in part, on tandemly repeated pentamers. A similar pentameric suborganization has been previously demonstrated for alpha satellite of the human X chromosome. Despite the organizational similarities, substantial sequence divergence distinguishes these subsets. Hybridization experiments indicate that the chromosome 17 and X subsets are more similar to each other than to the subsets found on several other human chromosomes. We suggest that the chromosome 17 and X alpha satellite subsets may be related components of a larger alphoid subfamily which have evolved from a common ancestral repeat into the contemporary chromosome-specific subsets.

scholarly journals Structure, organization, and sequence of alpha satellite DNA from human chromosome 17: evidence for evolution by unequal crossing-over and an ancestral pentamer repeat shared with the human X chromosome.

1986 ◽  
Vol 6 (9) ◽  
pp. 3156-3165 ◽  
Author(s):  
J S Waye ◽  
H F Willard
Keyword(s):  
Human Chromosome ◽  
X Chromosome ◽  
Repeat Unit ◽  
Higher Order ◽  
Chromosome 17 ◽  
Crossing Over ◽  
Human Chromosomes ◽  
Alpha Satellite ◽  
Unequal Crossing Over ◽  
Human Chromosome 17

The centromeric regions of all human chromosomes are characterized by distinct subsets of a diverse tandemly repeated DNA family, alpha satellite. On human chromosome 17, the predominant form of alpha satellite is a 2.7-kilobase-pair higher-order repeat unit consisting of 16 alphoid monomers. We present the complete nucleotide sequence of the 16-monomer repeat, which is present in 500 to 1,000 copies per chromosome 17, as well as that of a less abundant 15-monomer repeat, also from chromosome 17. These repeat units were approximately 98% identical in sequence, differing by the exclusion of precisely 1 monomer from the 15-monomer repeat. Homologous unequal crossing-over is suggested as a probable mechanism by which the different repeat lengths on chromosome 17 were generated, and the putative site of such a recombination event is identified. The monomer organization of the chromosome 17 higher-order repeat unit is based, in part, on tandemly repeated pentamers. A similar pentameric suborganization has been previously demonstrated for alpha satellite of the human X chromosome. Despite the organizational similarities, substantial sequence divergence distinguishes these subsets. Hybridization experiments indicate that the chromosome 17 and X subsets are more similar to each other than to the subsets found on several other human chromosomes. We suggest that the chromosome 17 and X alpha satellite subsets may be related components of a larger alphoid subfamily which have evolved from a common ancestral repeat into the contemporary chromosome-specific subsets.

CHROMOSOME EVOLUTION: REPETITIVE EUCHROMATIC CHROMOSOMAL SEGMENTS IN HAWAIIAN DROSOPHILA

1973 ◽  
Vol 15 (1) ◽  
pp. 171-175 ◽  
Author(s):  
Jong Sik Yoon ◽  
Marshall R. Wheeler
Keyword(s):  
Chromosome Evolution ◽  
Gene Action ◽  
Chromosomal Rearrangements ◽  
Rapid Evolution ◽  
Drosophila Species ◽  
Crossing Over ◽  
Hawaiian Drosophila ◽  
Unequal Crossing Over

We have found five distinct chromosomal regions which are repeated within the genomes of 11 endemic Hawaiian Drosophila species. One of the duplications was observed in more than 130 species (of three genera) of Hawaiian Drosophilidae. These "repeats" show synapsis in some nuclei, not in others; repeated segments are sometimes tandem while others are separated on their respective chromosomes. From these observations, one can speculate that chromosomal rearrangements produced by unequal crossing over due to such "repeats," and the possible development of new or modified gene action may provide, at least in part, an explanation of the remarkably rapid evolution and speciation in Hawaiian Drosophila.

Cloning and characterization of a transposable-like repeat in the heterochromatin of the darkling beetle Misolampus goudoti

Genome ◽  
2004 ◽  
Vol 47 (4) ◽  
pp. 769-774 ◽  
Author(s):  
Joan Pons
Keyword(s):  
Transposable Elements ◽  
Transposable Element ◽  
Satellite Dna ◽  
Molecular Mechanisms ◽  
Repeat Unit ◽  
Nucleotide Composition ◽  
Crossing Over ◽  
Unequal Crossing Over ◽  
Darkling Beetle

A long repeat unit of the PstI family in Misolampus goudoti (Coleoptera, Tenebrionodae) is characterized in this work. The 30 sequenced units have small differences in length (consensus 1169 bp), but very similar nucleotide composition (mean 61.1% A+T). PstI repeats contain a 36-bp-long inverted repeat at both the 5′ and 3′ ends, with a fully conserved 16-bp-long motif similar to those found in class II transposable elements. However, the transposable-like PstI repeats seems to be defective, since they do not encode for any protein related with transposition. Interestingly, energetically stable hairpins resembled the structure of a miniature interspersed transposable element, suggesting that the PstI satellite DNA family in M. goudoti may have originated from an ancestral active transposable element as also described in Drosophila guanche. The presence of transposable-like structure along with the non-detection of gene conversion or unequal crossing-over events suggest that transposition could be one of the putative molecular mechanisms involved in the strong amplification and (or) homogenization of these repeats. A putative transposition of PstI repeats allowing their genomic mobility also could explain why this satellite is widely distributed to all heterochromatic regions, telomeres, pericentromeric regions, and on the Y chromosome, whereas satellites of other tenebrionids lacking transposable-like structures are restricted only to pericentromeric regions.Key words: transposable elements, MITE, satellite DNA, heterochromatin, telomere, beetle, Tenebrionidae.

scholarly journals A Game of Thrones at Human Centromeres II. A new molecular/evolutionary model

2019 ◽  
Author(s):  
William R. Rice
Keyword(s):  
Tandem Repeats ◽  
Position Effect ◽  
Rapid Evolution ◽  
Evolutionary Model ◽  
Elevated Concentration ◽  
Position Effect Variegation ◽  
Repeat Array ◽  
Centromeric Repeat ◽  
New Form ◽  
Game Of Thrones

Human centromeres are remarkable in four ways: they are i) defined epigenetically by an elevated concentration of the histone H3 variant CENP-A, ii) inherited epigenetically by trans-generational cary-over of nucleosomes containing CENP-A, iii) formed over unusually long and complex tandem repeats (Higher Order Repeats, HORs) that extend over exceptionally long arrays of DNA (up to 8 Mb), and iv) evolve in such a rapid and punctuated manner that most HORs on orthologous chimp and human chromosomes are in different clades. What molecular and evolutionary processes generated these distinctive characteristics? Here I motivate and construct a new model for the formation, expansion/contraction, homogenization and rapid evolution of human centromeric repeat arrays that is based on fork-collapse during DNA replication (in response to proteins bound to DNA and/or collisions between DNA and RNA polymerases) followed by out-of-register re-initiation of replication via Break-Induced Repair (BIR). The model represents a new form of molecular drive. It predicts rapid and sometimes punctuated evolution of centromeric HORs due to a new form of intragenomic competition that is based on two features: i) the rate of tandem copy number expansion, and ii) resistance to invasion by pericentric heterochromatin within a centromere’s HOR array. These features determine which variant array elements will eventually occupy a pivotal region within a centromeric repeat array (switch-point) that gradually expands to populate the entire array. In humans, continuous HOR turnover is predicted due to intra-array competition between three repeat types with an intransitive hierarchy: A < B < C < A, where A = short, single-dimer HORs containing one monomer that binds centromere protein-B (CENP-B) and another that does not, B = moderately longer HORs composed of ≥ 2 dimers, and C = substantially longer HORs that lose their dimeric modular structure. Continuous turnover of proteins that bind centromeric DNA (but these proteins are not constituents of the kinetochore) and polygenic variation influencing position-effect variegation are predicted to cause rapid turnover of centromeric repeats in species lacking HORs and/or CENP-B binding at centromeres. Evolution at centromeres is a molecular ‘Game-of-Thrones’ because centromeric sequences ‘reign’ due to an epigenetic ‘crown’ of CENP-A that is perpetually ‘usurped’ by new sequences that more rapidly assemble large ‘armies’ of tandem repeats and/or resist ‘invasion’ from a surrounding ‘frontier’ of percentric heterochromatin. These ‘regal transitions’ occur in a backdrop of slashing and decapitation (fork-collapse generating truncated sister chromatids) in the context of promiscuous sex that is frequently incestuous (out-of-register BIR between sibling chromatids).

Mapping Unequal Crossing over Hotspot Region of Simple Sequence Repeat in Maize

2009 ◽  
Vol 35 (5) ◽  
pp. 958-961
Author(s):  
Ji-Hua TANG ◽  
Xi-Qing MA ◽  
Wen-Tao TENG ◽  
Jian-Bing YAN ◽  
Jing-Rui DAI ◽  
...  
Keyword(s):  
Simple Sequence Repeat ◽  
Crossing Over ◽  
Sequence Repeat ◽  
Unequal Crossing Over ◽  
Simple Sequence

scholarly journals UNEQUAL CROSSING OVER AT THE rRNA TANDON AS A SOURCE OF QUANTITATIVE GENETIC VARIATION IN DROSOPHILA

Genetics ◽  
1980 ◽  
Vol 95 (3) ◽  
pp. 727-742 ◽  
Author(s):  
R Frankham ◽  
D A Briscoe ◽  
R K Nurthen
Keyword(s):  
Genetic Variation ◽  
Selection Response ◽  
Crossing Over ◽  
Wild Type ◽  
X Chromosomes ◽  
Unequal Crossing Over ◽  
Quantitative Genetic ◽  
Y Chromosomes ◽  
Homozygous Line ◽  
Minimum Estimate

ABSTRACT Abdominal bristle selection lines (three high and three low) and controls were founded from a marked homozygous line to measure the contribution of sex-linked "mutations" to selection response. Two of the low lines exhibited a period of rapid response to selection in females, but not in males. There were corresponding changes in female variance, in heritabilities in females, in the sex ratio (a deficiency of females) and in fitness, as well as the appearance of a mutant phenotype in females of one line. All of these changes were due to bb alleles (partial deficiencies for the rRNA tandon) in the X chromosomes of these lines, while the Y chromosomes remained wild-type bb+. We argue that the bb alleles arose by unequal crossing over in the rRNA tandon.—A prediction of this hypothesis is that further changes can occur in the rRNA tandon as selection is continued. This has now been shown to occur.—Our minimum estimate of the rate of occurrence of changes at the rRNA tandon is 3 × 10-4. As this is substantially higher than conventional mutation rates, the questions of the mechanisms and rates of origin of new quantitative genetic variation require careful re-examination.

scholarly journals A Mutation of the Yeast Gene Encoding PCNA Destabilizes Both Microsatellite and Minisatellite DNA Sequences

Genetics ◽  
1999 ◽  
Vol 151 (2) ◽  
pp. 511-519 ◽  
Author(s):  
Robert J Kokoska ◽  
Lela Stefanovic ◽  
Andrew B Buermeyer ◽  
R Michael Liskay ◽  
Thomas D Petes
Keyword(s):  
Dna Polymerase ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Repeat Unit ◽  
Nuclear Antigen ◽  
Temperature Sensitive ◽  
Dinucleotide Repeats ◽  
Yeast Saccharomyces Cerevisiae ◽  
Dna Polymerase Δ ◽  
Repeat Units

AbstractThe POL30 gene of the yeast Saccharomyces cerevisiae encodes the proliferating cell nuclear antigen (PCNA), a protein required for processive DNA synthesis by DNA polymerase δ and ϵ. We examined the effects of the pol30-52 mutation on the stability of microsatellite (1- to 8-bp repeat units) and minisatellite (20-bp repeat units) DNA sequences. It had previously been shown that this mutation destabilizes dinucleotide repeats 150-fold and that this effect is primarily due to defects in DNA mismatch repair. From our analysis of the effects of pol30-52 on classes of repetitive DNA with longer repeat unit lengths, we conclude that this mutation may also elevate the rate of DNA polymerase slippage. The effect of pol30-52 on tracts of repetitive DNA with large repeat unit lengths was similar, but not identical, to that observed previously for pol3-t, a temperature-sensitive mutation affecting DNA polymerase δ. Strains with both pol30-52 and pol3-t mutations grew extremely slowly and had minisatellite mutation rates considerably greater than those observed in either single mutant strain.

Unequal Crossing-over in Unique PABP2 Mutations in Japanese Patients

2002 ◽  
Vol 59 (3) ◽  
pp. 474 ◽  
Author(s):  
Mika Nakamoto ◽  
Satoshi Nakano ◽  
Shingo Kawashima ◽  
Masafumi Ihara ◽  
Yo Nishimura ◽  
...  
Keyword(s):  
Japanese Patients ◽  
Crossing Over ◽  
Unequal Crossing Over
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