scholarly journals Spindle asymmetry drives non-Mendelian chromosome segregation

2017 ◽  
Author(s):  
Takashi Akera ◽  
Lukáš Chmátal ◽  
Emily Trimm ◽  
Karren Yang ◽  
Chanat Aonbangkhen ◽  
...  

Genetic elements compete for transmission through meiosis, when haploid gametes are created from a diploid parent. Selfish elements can enhance their transmission through meiotic drive, in violation of Mendel’s Law of Segregation. In female meiosis, selfish elements drive by preferentially attaching to the egg side of the spindle, which implies some asymmetry between the two sides of the spindle, but molecular mechanisms underlying spindle asymmetry are unknown. Here we show that CDC42 signaling from the cell cortex regulates microtubule tyrosination to induce spindle asymmetry, and non-Mendelian segregation depends on this asymmetry. These signals depend on cortical polarization directed by chromosomes, which are positioned near the cortex to allow the asymmetric cell division. Thus, selfish meiotic drivers exploit the asymmetry inherent in female meiosis to bias their transmission.

2021 ◽  
Author(s):  
Alberto Pineda-Santaella ◽  
Nazaret Fernández-Castillo ◽  
Alberto Jiménez-Martín ◽  
María del Carmen Macías-Cabeza ◽  
Ángela Sánchez-Gómez ◽  
...  

Chromosome segregation in female meiosis in many metazoans is mediated by acentrosomal spindles, the existence of which implies that microtubule spindles self-assemble without the participation of the centrosomes. Although it is thought that acentrosomal meiosis is not conserved in fungi, we recently reported the formation of self-assembled microtubule arrays, which were able to segregate chromosomes, in fission yeast mutants where the contribution of the spindle pole body (SPB, the centrosome equivalent in yeast) was specifically blocked during meiosis. Here, we demonstrate that this unexpected microtubule formation represents a bonafide type of acentrosomal spindle. Moreover, a comparative analysis of these self-assembled spindles and the canonical SPB-dependent spindle reveals similarities and differences: for example, both spindles have a similar polarity, but the location of the γ-tubulin complex differs. We also show that the robustness of self-assembled spindles can be reinforced by eliminating kinesin-8 family members, whereas kinesin-8 mutants have an adverse impact on SPB-dependent spindles. Hence, we consider that reinforced self-assembled spindles in yeast will help to clarify the molecular mechanisms behind acentrosomal meiosis, a crucial step towards better understanding gametogenesis.


Open Biology ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 210074
Author(s):  
Frances E. Clark ◽  
Takashi Akera

Female meiotic drive is the phenomenon where a selfish genetic element alters chromosome segregation during female meiosis to segregate to the egg and transmit to the next generation more frequently than Mendelian expectation. While several examples of female meiotic drive have been known for many decades, a molecular understanding of the underlying mechanisms has been elusive. Recent advances in this area in several model species prompts a comparative re-examination of these drive systems. In this review, we compare female meiotic drive of several animal and plant species, highlighting pertinent similarities.


2019 ◽  
Author(s):  
Nicholas B. Stewart ◽  
Yasir H. Ahmed-Braimah ◽  
Daniel G. Cerne ◽  
Bryant F. McAllister

AbstractA vast diversity of karyotypes exists within and between species, yet the mechanisms that shape this diversity are poorly understood. Here we investigate the role of biased meiotic segregation—i.e., meiotic drive—in karyotype evolution. The closely related species, Drosophila americana and D. novamexicana, provide an ideal system to investigate mechanisms of karyotypic diversification. Since their recent divergence, D. americana has evolved two centromeric fusions: one between the 2nd and 3rd chromosomes, and another between the X and 4th chromosomes. The 2-3 fusion is fixed in D. americana, but the X-4 fusion is polymorphic and varies in frequency along a latitudinal cline. Here we evaluate the hypothesis that these derived metacentric chromosomes segregate preferentially to the egg nucleus during female meiosis in D. americana. Using two different methods, we show that the fused X-4 chromosome is transmitted at an average frequency of ~57%, exceeding expectations of 50:50 Mendelian segregation. Three paracentric inversions are found in the vicinity of the X-4 fusion and could potentially influence chromosome segregation. Using crosses between lines with differing inversion arrangements, we show that the transmission bias persists regardless of inversion status. Transmission rates are also biased in D. americana/D. novamexicana hybrid females, favoring both the X-4 and 2-3 fused arrangements over their unfused homologs. Our results show that meiotic drive influences chromosome segregation in D. americana favoring derived arrangements in its reorganized karyotype. Moreover, the fused centromeres are the facilitators of biased segregation rather than associated chromosomal inversions.


2018 ◽  
Author(s):  
Stefanie Redemann ◽  
Ina Lantzsch ◽  
Norbert Lindow ◽  
Steffen Prohaska ◽  
Martin Srayko ◽  
...  

2001 ◽  
Vol 114 (23) ◽  
pp. 4319-4328
Author(s):  
Sherryl R. Bisgrove ◽  
Darryl L. Kropf

The first cell division in zygotes of the fucoid brown alga Pelvetia compressa is asymmetric and we are interested in the mechanism controlling the alignment of this division. Since the division plane bisects the mitotic apparatus, we investigated the timing and mechanism of spindle alignments. Centrosomes, which give rise to spindle poles, aligned with the growth axis in two phases – a premetaphase rotation of the nucleus and centrosomes followed by a postmetaphase alignment that coincided with the separation of the mitotic spindle poles during anaphase and telophase. The roles of the cytoskeleton and cell cortex in the two phases of alignment were analyzed by treatment with pharmacological agents. Treatments that disrupted cytoskeleton or perturbed cortical adhesions inhibited pre-metaphase alignment and we propose that this rotational alignment is effected by microtubules anchored at cortical adhesion sites. Postmetaphase alignment was not affected by any of the treatments tested, and may be dependent on asymmetric cell morphology.


2017 ◽  
Vol 23 (6) ◽  
pp. 706-722 ◽  
Author(s):  
Antonio Capalbo ◽  
Eva R Hoffmann ◽  
Danilo Cimadomo ◽  
Filippo Maria Ubaldi ◽  
Laura Rienzi

2019 ◽  
Author(s):  
Luiza Da Cunha Stankevicins ◽  
Marta Urbanska ◽  
Daniel AD. Flormann ◽  
Emmanuel Terriac ◽  
Zahra Mostajeran ◽  
...  

AbstractDendritic cells use amoeboid migration through constricted passages to reach the lymph nodes, and this homing function is crucial for immune responses. Amoeboid migration requires mechanical resilience, however, the underlying molecular mechanisms for this type of migration remain unknown. Because vimentin intermediate filaments (IFs) and microfilaments regulate adhesion-dependent migration in a bidirectional manner, we analyzed if they exert a similar control on amoeboid migration. Vimentin was required for cellular resilience, via a joint interaction between vimentin IFs and F-actin. Reduced actin mobility in the cell cortex of vimentin-reduced cells indicated that vimentin promotes Factin subunit exchange and dynamics. These mechano-dynamic alterations in vimentin-deficient dendritic cells impaired amoeboid migration in confined environments in vitro and blocked lymph node homing in mouse experiments in vivo. Correct nuclear positioning is important in confined amoeboid migration both to minimize resistance and to avoid DNA damage. Vimentin-deficiency also led to DNA double strand breaks in the compressed dendritic cells, pointing to a role of vimentin in nuclear positioning. Together, these observations show that vimentin IF-microfilament interactions provide both the specific mechano-dynamics required for dendritic cell migration and the protection the genome needs in compressed spaces.Summary statementVimentin — in joint action with actin — mediates the mechanical stiffness of cells required for amoeboid cell migration through confined spaces and protects the nucleus from DNA damage.


2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Bernardo Chapa-y-Lazo ◽  
Motonari Hamanaka ◽  
Alexander Wray ◽  
Mohan K. Balasubramanian ◽  
Masanori Mishima

Nearly six decades ago, Lewis Wolpert proposed the relaxation of the polar cell cortex by the radial arrays of astral microtubules as a mechanism for cleavage furrow induction. While this mechanism has remained controversial, recent work has provided evidence for polar relaxation by astral microtubules, although its molecular mechanisms remain elusive. Here, using C. elegans embryos, we show that polar relaxation is achieved through dynein-mediated removal of myosin II from the polar cortexes. Mutants that position centrosomes closer to the polar cortex accelerated furrow induction, whereas suppression of dynein activity delayed furrowing. We show that dynein-mediated removal of myosin II from the polar cortexes triggers a bidirectional cortical flow toward the cell equator, which induces the assembly of the actomyosin contractile ring. These results provide a molecular mechanism for the aster-dependent polar relaxation, which works in parallel with equatorial stimulation to promote robust cytokinesis.


2017 ◽  
Author(s):  
Kevin H-C Wei ◽  
Hemakumar M. Reddy ◽  
Chandramouli Rathnam ◽  
Jimin Lee ◽  
Deanna Lin ◽  
...  

AbstractMeiotic drive occurs when a selfish element increases its transmission frequency above the Mendelian ratio by hijacking the asymmetric divisions of female meiosis. Meiotic drive causes genomic conflict and potentially has a major impact on genome evolution, but only a few drive loci of large effect have been described. New methods to reliably detect meiotic drive are therefore needed, particularly for discovering moderate-strength drivers that are likely to be more prevalent in natural populations than strong drivers. Here we report an efficient method that uses sequencing of large pools of backcross (BC1) progeny to test for deviations from Mendelian segregation genome-wide of single-nucleotide polymorphisms (SNPs) that distinguish the parental strains. We show that meiotic drive can be detected by a characteristic pattern of decay in distortion of SNP frequencies, caused by recombination unlinking the driver from distal loci. We further show that control crosses allow allele-frequency distortion caused by meiotic drive to be distinguished from distortion resulting from developmental effects. We used this approach to test whether chromosomes with extreme telomere-length differences segregate at Mendelian ratios, as telomeric regions are a potential hotspot for meiotic drive due to their roles in meiotic segregation and multiple observations of high rates of telomere sequence evolution. Using four different pairings of long and short telomere strains, we find no evidence that extreme telomere-length variation causes meiotic drive in Drosophila. However, we identify one candidate meiotic driver in a centromere-linked region that shows an ~8% increase in transmission frequency, corresponding to a ~54:46 segregation ratio. Our results show that candidate meiotic drivers of moderate strength can be readily detected and localized in pools of F1 progeny.


2009 ◽  
Vol 80 (3) ◽  
pp. 555-562 ◽  
Author(s):  
Shufang Wang ◽  
Jianjun Hu ◽  
Xinzheng Guo ◽  
Johne X. Liu ◽  
Shaorong Gao

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