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Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes

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Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes G C A T T A C G G C A T genes Review Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes Filip Pajpach 1 , Tianyu Wu 2, Linda Shearwin-Whyatt 1 , Keith Jones 3 and Frank Grützner 1,* 1 School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia; fi[email protected] (F.P.); [email protected] (L.S.-W.) 2 Department of Central Laboratory, Clinical Laboratory, Jing’an District Centre Hospital of Shanghai and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; [email protected] 3 Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RH, UK; [email protected] * Correspondence: [email protected] Abstract: Segregation of chromosomes is a multistep process occurring both at mitosis and meiosis to ensure that daughter cells receive a complete set of genetic information. Critical components in the chromosome segregation include centromeres, kinetochores, components of sister chromatid and homologous chromosomes cohesion, microtubule organizing centres, and spindles. Based on the cytological work in the grasshopper Brachystola, it has been accepted for decades that segregation of homologs at meiosis is fundamentally random. This ensures that alleles on chromosomes have equal chance to be transmitted to progeny. At the same time mechanisms of meiotic drive and an increasing number of other examples of non-random segregation of autosomes and sex chromosomes provide insights into the underlying mechanisms of chromosome segregation but also question the textbook Citation: Pajpach, F.; Wu, T.; dogma of random chromosome segregation. Recent advances provide a better understanding of Shearwin-Whyatt, L.; Jones, K.; meiotic drive as a prominent force where cellular and chromosomal changes allow autosomes to Grützner, F. Flavors of Non-Random bias their segregation. Less understood are mechanisms explaining observations that autosomal Meiotic Segregation of Autosomes heteromorphism may cause biased segregation and regulate alternating segregation of multiple sex and Sex Chromosomes. Genes 2021, chromosome systems or translocation heterozygotes as an extreme case of non-random segregation. 12, 1338. https://doi.org/10.3390/ We speculate that molecular and cytological mechanisms of non-random segregation might be genes12091338 common in these cases and that there might be a continuous transition between random and non- random segregation which may play a role in the evolution of sexually antagonistic genes and sex Academic Editors: Frederic Veyrunes, chromosome evolution. Frederic Baudat and Jesús Page Utrilla Keywords: non-random segregation; meiotic drive; sex chromosome Received: 15 July 2021 Accepted: 26 August 2021 Published: 28 August 2021 1. Delving into History: The First Evidence of Random Segregation of Chromosomes at Meiosis Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in The history of chromosome segregation dates back from the time when the link be- published maps and institutional affil- tween Mendelian genetics and behavior of chromosomes during meiosis was formed based iations. on the studies of Walter Stanborough Sutton in 1903. Already knowing that homologous chromosomes form pairs, Sutton observed segregation of such homologs during meiosis in the grasshopper Brachystola. Although he misidentified the second meiotic division as the reducing one, he claimed that the orientation of homologous chromosomes in the equato- rial plate is “purely a matter of chance” [1]. However, as he also acknowledged, he brought Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. no definitive evidence due to the inability to reliably distinguish between the paternal This article is an open access article and maternal chromosomes of any given autosome pair. Ten years later, Estella Eleanor distributed under the terms and Carothers came up with the cytological evidence of what had been proposed by Sutton conditions of the Creative Commons before—that is, if genes are to be assorted independently, chromosomes bearing these Attribution (CC BY) license (https:// genes should segregate randomly. After the discovery of a single heteromorphic autosome creativecommons.org/licenses/by/ pair in grasshopper, Carothers carefully observed distinguishable heteromorphic chromo- 4.0/). somes during the first meiotic division in Brachystola. She noticed that one heteromorphic Genes 2021, 12, 1338. https://doi.org/10.3390/genes12091338 https://www.mdpi.com/journal/genes Genes 2021, 12, 1338 2 of 22 somes bearing these genes should segregate randomly. After the discovery of a single het- eromorphic autosome pair in grasshopper, Carothers carefully observed distinguishable Genes 2021, 12, 1338 2 of 22 heteromorphic chromosomes during the first meiotic division in Brachystola. She noticed that one heteromorphic homolog segregates together with the accessory (sex) chromo- homologsome with segregates approximately together equal with frequency the accessory compared (sex) chromosometo the other homolog with approximately (Figure 1) [2]. equalThese frequency results fundamentally compared to the led other to the homolog establishment (Figure1 of)[ what2]. These has resultsbecome fundamentally a dogma in bi- ledology–chromosomes to the establishment segregate of what hasrandomly become at a meio dogmasis. in At biology–chromosomes the time when the first segregate evidence randomlyof non-random at meiosis. segregation At the time of the when segregation the first evidencedistorter ofin non-randomDrosophila was segregation discovered of there the segregationwere no powerful distorter tools in Drosophila to study wasthe relati discoveredonship therebetween were chromosome no powerful segregation tools to study and thefactors relationship that control between and chromosomeinfluence this segregation segregation. and In addition factors that to that, control this and dogma influence was in thisagreement segregation. with Inthe addition Mendelian to that,laws–something this dogma wasmore in easily agreement demonst withrated the than Mendelian physical laws–somethingchromosome movement. more easily Now, demonstrated over 100 years than la physicalter, there chromosome is increasing movement. evidence and Now, un- overderstanding 100 years of later, the therefactors is that increasing control evidencerandom segregation and understanding and these of are the factorssubsequently that controldiscussed. random segregation and these are subsequently discussed. FigureFigure 1. 1.Carothers’ Carothers’ observation observation in in the the grasshopper grasshopperBrachystola Brachystola—the—the frequency frequency of of accessory accessory (sex) (sex) chromosomechromosome segregation segregation together together with with either either chromosome chromosome belonging belonging to to the the heteromorphic heteromorphic pair pair is is roughlyroughly the the same; same; this this led led to to conclusion conclusion that that chromosome chromosome segregation segregation is is generally generally random. random. 2.2. Building Building Blocks Blocks of of Chromosome Chromosome Segregation Segregation InIn order order to to successfully successfully divide divide genetic genetic information information to to daughter daughter cells, cells, chromosomes chromosomes undergoundergo a a complex complex process process of of segregation. segregation. During During cell cell division, division, kinetochores kinetochores must must form form onon centromeres centromeres of of each each chromosome. chromosome. After After kinetochores kinetochores are are assembled, assembled, chromosomes chromosomes nownow possess possess a a structure structure thanks thanks to to which which they they can can be be attached attached to to microtubules microtubules of of a spindlea spindle apparatus,apparatus, which which undergoes undergoes the the process process of of its it owns own assembly. assembly. Once Once kinetochores kinetochores of of all all chromosomes are attached to spindle microtubules, a multistep journey of chromosomes chromosomes are attached to spindle microtubules, a multistep journey of chromosomes to daughter cells can commence. Chromosome segregation is a highly regulated process to daughter cells can commence. Chromosome segregation is a highly regulated process occurring during both mitotic and meiotic divisions and involving many other components, occurring during both mitotic and meiotic divisions and involving many other compo- including microtubule organising centre (MTOC), components of sister chromatid cohe- nents, including microtubule organising centre (MTOC), components of sister chromatid sion and pairing of homologous chromosomes, and much more. Individual components cohesion and pairing of homologous chromosomes, and much more. Individual compo- are subsequently discussed in relation to how they act to ensure that chromosomes are nents are subsequently discussed in relation to how they act to ensure that chromosomes segregated to daughter cells. are segregated to daughter cells. 2.1. Centromeres—Not Just Construction Sites for Building Kinetochores The centromere is an important structure for proper chromosome separation ensuring that only one copy of each chromosome segregates to each daughter cell during cell division. The centromere was initially observed in 1882 and termed in 1936, after that its crucial Genes 2021, 12, 1338 3 of 22 2.1. Centromeres—Not Just Construction
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