Study Gives First View Of Centromere Variation And Evolution
A genomic study of human and selected nonhuman primate centromeres has revealed their unimaginable diversity and speed of evolutionary change.
In cell genetics, a centromere is the spot where two sister chromatids attach. A chromatid is one-half of a duplicated chromosome. United pairs of chromosomes have identifiable shapes because centromeres are not in a uniform position. As a cell prepares to divide, the machinery to separate and segregate chromosomes goes into action at each centromere location.
Unless the genetic material is distributed correctly between the two resulting cells, problems can arise. These include cancer, congenital disorders such as Down syndrome, and the inability of a fertilized cell to grow into a baby.
Although centromeres are vital to proper cell replication, the complexity of their genomic organization had been almost impossible to study. The lack of centromere sequences hindered exploration of how these regions help maintain genetic integrity.
Today, advances in long-read genome sequencing technologies, refined computerized genome assembly algorithms, and improved genome databases are enabling scientists to realize how greatly centromeres differ in size and structure. This opens new avenues toward figuring out what these differences might mean.
A first look at the factors behind the vast variations in centromeres is reported today, April 3, in Nature. The findings suggest that centromeres are likely highly individualized among people. A set of centromeres might even be a personal signature, just as we each have characteristic voice patterns, iris colorations and fingerprints that distinguish us from one another.
It's not yet known if certain centromere variations might make people susceptible to particular diseases.
Only the human X chromosome appears to be mostly immutable, with very similar sequences and structure across a diversity of humans.
The lead author of the Nature report is Glennis Logsdon, a recent postdoctoral scholar in Evan Eichler's genomic science lab at the University of Washington School of Medicine in Seattle. Logsdon is now a faculty member at the Perelman School of Medicine at the University of Pennsylvania. Eichler, who is also a Howard Hughes Medical Institute Investigator and a member of the Brotman Baty Institute for Precision Medicine, is the senior and corresponding author.
"This recent research is a direct application of both the Human Pangenome Reference Consortium and the Telomere-to-Telomere (T2T) sequencing efforts to provide new biological insights into complex regions of the human genome critical for chromosome segregation," noted Eichler. He is known for his work on genome evolution and its potential to create new functions and also for studies of genetic instability associated with disease.
To capture information on how human centromeres might have evolved, the team compared human genetic sequences of two completely sequenced human centromeres with those of some nonhuman primates. These were the chimpanzee and the orangutan, which are great apes and closely related species to humans, and the macaque, an Old World monkey and a more distant relative.
The scientists discovered that centromeres have been evolving much faster than other unique portions of the human genome. They are among the most mutation-prone regions of the human genome. The researchers also found that the unique sequences and structure of centromeres were the culmination of different evolutionary forces moving at different rates.
"The rapid mutation of the centromeric regions of the genome, along with their various mutation rates, has led to their diverse structure and organization," Logsdon noted. It was surprising to learn, the scientists said, that such vital areas of the genome were subject to swift changes, because, in general, critical functions tend to be genetically conserved.
The scientists plan to expand these initial efforts by developing more genetic maps of centromeres in diverse human genomes and across various organs and tissues, and to perform multigeneration family studies of centromere sequences. The complete sequence of centromeres from other nonhuman primates will provide a better model of the evolutionary forces shaping these regions.
Peering into the future, Logsdon and her team hope someday to apply their findings on centromeres to the design and engineering of customized human artificial chromosomes to transform medical science. Several years ago, Logsdon and her mentors worked on efforts to develop human artificial chromosomes that bypass centromeric DNA, which had then posed a constraint to mammalian synthetic genome research. Logsdon and others recently published another study last week in Science, which showed that enlarging the artificial chromosome DNA vector allowed for efficient formation of human artificial chromosomes in cells.
The centromere studies reported today were supported by funding from the National Institutes of Health National Human Genome Research Institute (R01 HG010169); National Institute of General Medical Sciences (K99 GM147352 ); National Cancer Institute (R01 CA266339); Intramural Research Program of the National Human Genome Research Institute; Shanghai Jiao Tong University 2030 Program (WH510363001-7); Center for Integration in Science of the Ministry of Aliyah, Israel; and the Howard Hughes Medical Institute. This work utilized the computational resources of the National Institutes of Health High Performance Computing Biowulf Linux cluster.
Method of ResearchExperimental study
Article TitleThe variation and evolution of complete human centromeres
Article Publication Date3-Apr-2024
COI StatementSergey Nurk is now an employee of Oxford Nanopore Technologies, Inc.; Sergey Koren has received travel funds to speak at events hosted by Oxford Nanopore Technologies, Inc.; Evan E. Eichler is a scientific advisory board member of Variant Bio, Inc.
Disclaimer: AAAS and EurekAlert! Are not responsible for the accuracy of news releases posted to EurekAlert! By contributing institutions or for the use of any information through the EurekAlert system.
Wetin Be Down Syndrome?
Wia dis foto come from, Getty Images
21 March 2024
Di international day to raise public awareness around Down syndrome (DS) na on 21 March.
United Nations don dey officially observe World Down Syndrome Day since 2012.
E dey fall on di 21st day of di third month of di year, "to signify di uniqueness of di triplication (trisomy) of di 21st chromosome wey dey cause Down syndrome", organisers tok.
Dis year theme na 'End di Stereotypes.' E aim to fight di idea about pipo wit Down syndrome and wetin dem fit be like or wetin dem fit do.
Wetin e be?
Down syndrome na wen dem born pikin wit extra chromosome. Di genetic condition dey affect pesin learning and physical features.
E no be disease, illness or condition wey pesin fit catch. Down syndrome dey happun naturally - e no get cause.
Pipo wey dem born wit am usually get extra chromosome by chance, becos of change in di sperm or egg before dem born di pikin.
E dey exist in all regions across di globe and dey commonly result in different effects on learning styles, physical characteristics and health, UN tok.
We get three types: trisomy 21 (wey be di most common type - wia three copies of chromosome 21 dey), translocation and mosaicism.
Di syndrome imself dey named afta Dr John Langdon Down wey be di first pesin to categorise am.
Wetin be di five signs of Down syndrome?
Wia dis foto come from, Getty Images
Wetin we call dis foto,E get some physical characteristics of Down syndrome
Physical signs fit include:
(Source: US Centers for Disease Control and Prevention)
Any treatment dey for Down syndrome?
Wia dis foto come from, Getty Images
Wetin we call dis foto,Di quality of life of pipo wit DS fit improve by looking afta dia health care needs
Treatments no dey for di syndrome.
Dem fit give help base on each pesin physical and intellectual need, strength, and limitation.
Adequate access to health care, early intervention programme and inclusive education, as well as correct research, dey important to di growth and development of di individual, UN tok.
Di quality of life of pipo wit Down syndrome (DS) fit see improvement by meeting dia health care need, e add.
Dis fit include regular check-ups wit health professionals to monitor mental and physical condition and to provide timely intervention such as physiotherapy, occupational therapy, speech therapy, counselling or special education, e tok.
Dis one dey facilitate dia participation in mainstream society and di fulfilment of dia personal potential.
Wia dis foto come from, Getty Images
Wetin we call dis foto,Many wit DS fit go school and work
Many dey live good quality of life, attend mainstream school and work, and some dey marry and live independently.
Some get secured high-profile jobs, such as Mar Galcerán for Spain, wey dem elect as lawmaker for Valencia regional assembly for di east of di kontri.
She be di first pesin wit di condition to join European regional or national parliament.
Wia dis foto come from, Getty Images
Wetin we call dis foto,Mar Galcerán
Also Ellie Goldstein dey, wey don make history as di first model wit DS to feature on di front cover of Vogue - even though doctors don tok say she no go fit waka or tok becos of di syndrome.
And Heidi Crowter na British disability rights activist wit DS wey dey challenge law wey dey allow make dem fit comot foetuses wit di condition up until birth.
She don take her case to di European Court of Human Rights. She tok say di current rules dey discriminatory.
Topics Wey Dem Resemble
Another thing we de for inside dis tori
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