- Email: [email protected]
Evolution: A Mosaic-type Centromere in an Early-Diverging Fungus
Current Biology
Dispatches 16. Van Der Werf, Y.D., Altena, E., Schoonheim, M.M., Sanz-Arigita, E.J., Vis, J.C., De Rijke, W., and Van Someren, E.J. (2009). Sleep benefits subsequent hippocampal functioning. Nat. Neurosci. 12, 122–123. 17. Marshall, L., Helgadottir, H., Molle, M., and Born, J. (2006). Boosting slow oscillations
during sleep potentiates memory. Nature 444, 610–613. 18. Donlea, J.M. (2019). Roles for sleep in memory: insights from the fly. Curr. Opin. Neurobiol. 54, 120–126. 19. Seidner, G., Robinson, J.E., Wu, M., Worden, K., Masek, P., Roberts, S.W., Keene, A.C., and
Joiner, W.J. (2015). Identification of neurons with a privileged role in sleep homeostasis in Drosophila melanogaster. Curr. Biol. 25, 2928– 2938. 20. van Alphen, B., Yap, M.H., Kirszenblat, L., Kottler, B., and van Swinderen, B. (2013). A dynamic deep sleep stage in Drosophila. J. Neurosci. 33, 6917–6927.
Evolution: A Mosaic-type Centromere in an Early-Diverging Fungus Bungo Akiyoshi Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.09.042
Centromeres in eukaryotes can be classified into three categories: point centromeres, regional centromeres, or holocentric. Now, a hybrid-type centromere is found in a pathogenic fungus that lacks the key kinetochore component CENP-A. Accurate duplication and transmission of genetic material is essential for the survival of all organisms. Centromeres are chromosomal regions that promote accurate segregation of duplicated chromosomes in eukaryotes. They do so by serving as the platform for a macromolecular protein complex called the kinetochore, which governs chromosome movements by interacting with dynamic polymers called spindle microtubules [1]. Despite its importance for genetic inheritance, the DNA sequence at centromeres evolves rapidly and centromere size varies drastically among eukaryotes — ranging from a 125base pair point centromere in budding yeast to several megabase pair regional centromeres in humans [2–4]. While centromeres in these organisms are confined to one region (called monocentric), there are species that have centromeres dispersed across whole chromosomes (holocentric). It is thought that kinetochore assembly sites are not determined by specific DNA sequence in most eukaryotes (except for budding yeast that has a genetically-defined point centromere [5]). Although centromeres were recognized more than a century ago, active research is still going on to determine how kinetochore assembly
sites are specified and maintained at centromeres in a sequence-independent manner. CENP-A is a centromere-specific histone H3 variant that marks kinetochore positions in many eukaryotes [1]. It also plays an important role in kinetochore assembly by recruiting other kinetochore proteins to centromeres. However, CENP-A is absent in some insects (e.g., silkworms [6]) and kinetoplastids (e.g., trypanosomes [7]). Furthermore, a recent bioinformatics survey found the putative absence of CENP-A in early-diverging fungi that belong to the order Mucorales of the subphylum Mucoromycotina (Mucor circinelloides and Phycomyces blakesleeanus) [8]. Understanding how these organisms manage to accomplish conserved kinetochore functions without CENP-A could provide deeper insights into the mechanism of kinetochore specification and assembly in eukaryotes. Although it has been shown that CENP-Aless insects have holocentric chromosomes [6] and that kinetoplastids have monocentric chromosomes [9,10], it remained unknown what type of centromere is present in Mucoromycotina. A new study by Navarro-Mendoza et al., published in this issue of Current Biology, addressed this
question, which led to an exciting discovery of a hitherto unknown type of centromere [11]. To systematically examine the presence or absence of CENP-A in earlydiverging fungi, the authors first examined the genome of 55 Mucoromycotina species as well as 20 species from other fungal clades. Mucoromycotina is subdivided into three orders: Mucorales, Umbelopsidales, and Endogonalean. Their analysis found that CENP-A is absent in all Mucorales and Umbelopsidales, but is present in Endogonalean and other fungal clades, suggesting that CENP-A was present in the last Mucoromycotina common ancestor but was lost in the common ancestor of Mucorales and Umbelopsidales. Interestingly, CENP-C, a binding partner of CENP-A, was also lost in Mucorales. Loss of both CENP-A and CENP-C is found in certain insects, which in all known cases is associated with a transition to holocentricity [6]. To reveal what kind of centromere is present in Mucorales, the authors had a closer look into the fungi. Although it is often difficult to work on early-diverging fungi, a good amount of molecular tools is available in Mucor circinelloides [12], so they decided to examine this pathogenic
R1184 Current Biology 29, R1174–R1198, November 18, 2019 ª 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Current Biology
Dispatches Mucorales. They first tagged three kinetochore proteins (Mis12, Dsn1, and CENP-T) with fluorescent tags and found multiple punctate signals in the nucleus, suggesting that this organism has monocentric, rather than holocentric, chromosomes, despite the absence of CENP-A and CENP-C. To map the position of centromeres, they performed chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) for two kinetochore proteins (Mis12 and Dsn1). Nine peaks were observed by this approach, each having a major and minor signal. As expected, only one peak was found per chromosome, strongly suggesting that the peak corresponds to the core centromere where kinetochore proteins bind (Figure 1). The average length of the core centromeres is 1 kb, which are surrounded by gene-free pericentric regions (15 to 75 kb), where transposable elements are present (Figure 1). The sequence analysis revealed that these retrotransposons belong to the LINE1 clade, so the authors termed them genomic retrotransposable element of Mucoromycotina (Grem) LINE1. GremLINE1s are found specifically in the pericentric regions in Mucor circinelloides, often orienting away from the core centromeres. These elements therefore form large inverted repeats, a feature also found in some eukaryotes [13,14]. Interestingly, Grem-like elements are present in other Mucorales and Umbelopsidales (organisms without CENP-A), but not in Endogonalean (organisms with CENP-A), suggesting that Grem-LINE1s might play an important role in CENP-A-less Mucoromycotina. Transposable elements are present at centromeres in various species [15], while RNAi machinery is important for controlling the mobility of transposable elements and maintaining centromere structure and stability [16]. Mucor circinelloides has an elaborate RNAi system that protects its genome against invading elements or movement of transposable elements [17]. Indeed, the authors found that the Grem-LINE1s in the pericentric regions are silenced by the Dicer-dependent RNAi machinery. It will be important to test whether the RNAi machinery or Grem-LINE1s influence centromere functions in Mucor circinelloides.
CEN 4
Chromosome 4
Major signal Minor signal Kinetochore protein ChIP
Pericentric region Core Grem-LINE1 Grem-LINE1
Pericentric region
Grem-LINE1 Grem-LINE1 Grem-LINE1
Centromere-specific 41-bp sequence motif AT-rich Major peak
Centromere (~30 kb) Core centromere region (~1 kb)
Minor peak Current Biology
Figure 1. Mucor circinelloides centromere is a mosaic of point and regional centromere qualities. Schematic of the centromere region of chromosome 4 is shown. ChIP-seq of kinetochore proteins shows a single peak (major and minor signal) that marks the 1 kb core centromere region, which is surrounded by 30 kb pericentric regions that harbour Grem-LINE1 transposable elements. The core centromere has a centromere-specific 41-bp sequence motif and a highly AT-rich sequence stretch.
It is clear from these results that the centromere of this organism is regional despite the absence of CENP-A, but a further surprise was hidden in its sequence. So far, the only known specific DNA sequence present in the core centromere region is in budding yeasts that have point centromeres [5,18]. It was therefore unexpected that the authors identified a 41-bp unique DNA sequence motif that is present in all nine core centromeres, but is absent from any other chromosomal region. They also noticed that the minor signal of kinetochore proteins in the core centromere region was spaced by a highly AT-rich stretch followed by the major signal that starts with the 41-bp motif (Figure 1). Although the significance of the major and minor signals remains unclear, the major signal likely reflects a binding site for some kinetochore proteins that may directly bind the 41-bp motif. The presence of a unique sequence in Mucor circinelloides means that its centromere is a mosaic of point and regional centromeres, which represents an exciting discovery in centromere biology. It is thought that geneticallydefined centromeres are prone to exploitation by selfish DNA that hijacks the host segregation machinery (e.g., 2-micron plasmid in S. cerevisiae [19]). Although it remains unknown whether the centromere of Mucor circinelloides is genetically or epigenetically defined, it will be interesting to reveal the advantage or
disadvantage of having specific DNA sequence at centromeres. There are now at least three distinct groups of eukaryotes that lack CENP-A: certain insect lineages, Mucorales, and kinetoplastids. While it remains controversial whether kinetoplastids that have unconventional kinetochore proteins ancestrally possessed CENP-A or not [7,20], those insects and Mucorales that have otherwise canonical kinetochore components most likely lost CENP-A [6,11]. Why did those insects acquire holocentricity, while Mucor circinelloides remains monocentric? What kind of changes in kinetochore compositions happened immediately after the loss of CENP-A in these organisms? Furthermore, what is the advantage of having CENP-A or not having CENP-A? Although it is well known that centromeres in many species are relatively AT-rich, its significance remains unclear. It is noteworthy that the ATrichness at centromeres is also found in Mucor circinelloides and Trypanosoma brucei, species that do not have CENP-A but have functional RNAi machinery, suggesting that factors such as production of non-coding RNA might have something to do with the ATrichness. Finally, it is important to mention that understanding the biology of this pathogenic fungus has medical relevance. It is possible that there is a unique kinetochore protein that binds the 41-bp motif, which could represent a target. In any case, understanding the
Current Biology 29, R1174–R1198, November 18, 2019 R1185
Current Biology
Dispatches kinetochore in Mucor circinelloides will lead to important insights into the mechanism of kinetochore specification and assembly.
8. van Hooff, J.J., Tromer, E., van Wijk, L.M., Snel, B., and Kops, G.J. (2017). Evolutionary dynamics of the kinetochore network in eukaryotes as revealed by comparative genomics. EMBO Rep. 18, 1559–1571.
REFERENCES
9. Obado, S.O., Bot, C., Nilsson, D., Andersson, B., and Kelly, J.M. (2007). Repetitive DNA is associated with centromeric domains in Trypanosoma brucei but not Trypanosoma cruzi. Genome Biol. 8, R37.
1. Musacchio, A., and Desai, A. (2017). A molecular view of kinetochore assembly and function. Biology 6, https://doi.org/10.3390/ biology6010005. 2. Henikoff, S., Ahmad, K., and Malik, H.S. (2001). The centromere paradox: stable inheritance with rapidly evolving DNA. Science 293, 1098–1102. 3. Cleveland, D.W., Mao, Y., and Sullivan, K.F. (2003). Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 112, 407–421. trovic , N., and Mravinac, B. 4. Plohl, M., Mes (2014). Centromere identity from the DNA point of view. Chromosoma 123, 313–325. 5. Clarke, L., and Carbon, J. (1980). Isolation of a yeast centromere and construction of functional small circular chromosomes. Nature 287, 504–509. 6. Drinnenberg, I.A., deYoung, D., Henikoff, S., and Malik, H.S. (2014). Recurrent loss of CenH3 is associated with independent transitions to holocentricity in insects. Elife 3, e03676. 7. Akiyoshi, B., and Gull, K. (2014). Discovery of unconventional kinetochores in kinetoplastids. Cell 156, 1247–1258.
10. Garcia-Silva, M.-R., Sollelis, L., MacPherson, C.R., Stanojcic, S., Kuk, N., Crobu, L., Bringaud, F., Bastien, P., Page`s, M., Scherf, A., et al. (2017). Identification of the centromeres of Leishmania major: revealing the hidden pieces. EMBO Rep. 18, 1968–1977. 11. Navarro-Mendoza, M.-I., Perez-Arques, C., Panchal, S., Nicolas, F.E., Mondo, S.J., Ganguly, P., Pangilinan, J., Grigoriev, I.V., Heitman, J., Sanyal, K., and Garre, V. (2019). Early diverging fungus Mucor circinelloides lacks centromeric histone CENP-A and displays a mosaic of point and regional centromeres. Curr. Biol. 29, 3791–3802.
structure in fission yeast centromere. Mol. Biol. Cell 3, 819–835. 14. Chatterjee, G., Sankaranarayanan, S.R., Guin, K., Thattikota, Y., Padmanabhan, S., Siddharthan, R., and Sanyal, K. (2016). Repeat-associated fission yeast-like regional centromeres in the Ascomycetous budding yeast Candida tropicalis. PLoS Genet. 12, e1005839. 15. Hartley, G., and O’Neill, R.J. (2019). Centromere repeats: Hidden gems of the genome. Genes (Basel) 10, 233. 16. Yadav, V., Sun, S., Billmyre, R.B., Thimmappa, B.C., Shea, T., Lintner, R., Bakkeren, G., Cuomo, C.A., Heitman, J., and Sanyal, K. (2018). RNAi is a critical determinant of centromere evolution in closely related fungi. Proc. Natl. Acad. Sci. USA 115, 3108–3113. 17. Torres-Martı´nez, S., and Ruiz-Va´zquez, R.M. (2016). RNAi pathways in Mucor: A tale of proteins, small RNAs and functional diversity. Fung. Genet. Biol. 90, 44–52. 18. Kobayashi, N., Suzuki, Y., Schoenfeld, L.W., Mu¨ller, C.A., Nieduszynski, C., Wolfe, K.H., and Tanaka, T.U. (2015). Discovery of an unconventional centromere in budding yeast redefines evolution of point centromeres. Curr. Biol. 25, 2026–2033.
rez12. Nicola´s, F.E., Navarro-Mendoza, M.I., Pe Arques, C., Lo´pez-Garcı´a, S., Navarro, E., Torres-Martı´nez, S., and Garre, V. (2018). Molecular tools for carotenogenesis analysis in the mucoral Mucor circinelloides. In Microbial Carotenoids: Methods and Protocols Methods in Molecular Biology., C. Barreiro, and J.-L. Barredo, eds. (New York, NY: Springer New York), pp. 221–237.
19. Malik, H.S., and Henikoff, S. (2009). Major evolutionary transitions in centromere complexity. Cell 138, 1067–1082.
13. Takahashi, K., Murakami, S., Chikashige, Y., Funabiki, H., Niwa, O., and Yanagida, M. (1992). A low copy number central sequence with strict symmetry and unusual chromatin
20. Tromer, E.C., van Hooff, J.J.E., Kops, G.J.P.L., and Snel, B. (2019). Mosaic origin of the eukaryotic kinetochore. Proc. Natl. Acad. Sci. USA 116, 12873–12882.
Plant Biology: To Live, or Not to Live, That Is the Question Alice Y. Cheung Department of Biochemistry and Molecular Biology, Molecular and Cell Biology Program, Plant Biology Program, University of Massachusetts, Amherst, MA, USA Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.09.057
Organisms tread a fine line in balancing the decision to maintain cellular homeostasis or promote cell death to allow for renewal during development or halt the spread of a life-threatening crisis. Recent studies suggest a labyrinth of receptor kinase–cyclic nucleotide-gated ion channel connections mediates life-and-death decisions in plants. Triggering cell death is a strategy crucial for organisms to maintain life and survive in times of encountering challenges that threaten their well-being. In plants, cell death underlies important developmental
processes, such as the differentiation of the vascular system, development of root system architecture, sex differentiation, and production of fertile reproductive cells [1]. Local cell death is also crucial in
containing the damage incurred by pathogens at their invasion sites to prevent systemic spreading of diseases. Mechanistic understanding of how cell death is regulated in plants remains sparse.
R1186 Current Biology 29, R1174–R1198, November 18, 2019 ª 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Dispatches 16. Van Der Werf, Y.D., Altena, E., Schoonheim, M.M., Sanz-Arigita, E.J., Vis, J.C., De Rijke, W., and Van Someren, E.J. (2009). Sleep benefits subsequent hippocampal functioning. Nat. Neurosci. 12, 122–123. 17. Marshall, L., Helgadottir, H., Molle, M., and Born, J. (2006). Boosting slow oscillations
during sleep potentiates memory. Nature 444, 610–613. 18. Donlea, J.M. (2019). Roles for sleep in memory: insights from the fly. Curr. Opin. Neurobiol. 54, 120–126. 19. Seidner, G., Robinson, J.E., Wu, M., Worden, K., Masek, P., Roberts, S.W., Keene, A.C., and
Joiner, W.J. (2015). Identification of neurons with a privileged role in sleep homeostasis in Drosophila melanogaster. Curr. Biol. 25, 2928– 2938. 20. van Alphen, B., Yap, M.H., Kirszenblat, L., Kottler, B., and van Swinderen, B. (2013). A dynamic deep sleep stage in Drosophila. J. Neurosci. 33, 6917–6927.
Evolution: A Mosaic-type Centromere in an Early-Diverging Fungus Bungo Akiyoshi Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.09.042
Centromeres in eukaryotes can be classified into three categories: point centromeres, regional centromeres, or holocentric. Now, a hybrid-type centromere is found in a pathogenic fungus that lacks the key kinetochore component CENP-A. Accurate duplication and transmission of genetic material is essential for the survival of all organisms. Centromeres are chromosomal regions that promote accurate segregation of duplicated chromosomes in eukaryotes. They do so by serving as the platform for a macromolecular protein complex called the kinetochore, which governs chromosome movements by interacting with dynamic polymers called spindle microtubules [1]. Despite its importance for genetic inheritance, the DNA sequence at centromeres evolves rapidly and centromere size varies drastically among eukaryotes — ranging from a 125base pair point centromere in budding yeast to several megabase pair regional centromeres in humans [2–4]. While centromeres in these organisms are confined to one region (called monocentric), there are species that have centromeres dispersed across whole chromosomes (holocentric). It is thought that kinetochore assembly sites are not determined by specific DNA sequence in most eukaryotes (except for budding yeast that has a genetically-defined point centromere [5]). Although centromeres were recognized more than a century ago, active research is still going on to determine how kinetochore assembly
sites are specified and maintained at centromeres in a sequence-independent manner. CENP-A is a centromere-specific histone H3 variant that marks kinetochore positions in many eukaryotes [1]. It also plays an important role in kinetochore assembly by recruiting other kinetochore proteins to centromeres. However, CENP-A is absent in some insects (e.g., silkworms [6]) and kinetoplastids (e.g., trypanosomes [7]). Furthermore, a recent bioinformatics survey found the putative absence of CENP-A in early-diverging fungi that belong to the order Mucorales of the subphylum Mucoromycotina (Mucor circinelloides and Phycomyces blakesleeanus) [8]. Understanding how these organisms manage to accomplish conserved kinetochore functions without CENP-A could provide deeper insights into the mechanism of kinetochore specification and assembly in eukaryotes. Although it has been shown that CENP-Aless insects have holocentric chromosomes [6] and that kinetoplastids have monocentric chromosomes [9,10], it remained unknown what type of centromere is present in Mucoromycotina. A new study by Navarro-Mendoza et al., published in this issue of Current Biology, addressed this
question, which led to an exciting discovery of a hitherto unknown type of centromere [11]. To systematically examine the presence or absence of CENP-A in earlydiverging fungi, the authors first examined the genome of 55 Mucoromycotina species as well as 20 species from other fungal clades. Mucoromycotina is subdivided into three orders: Mucorales, Umbelopsidales, and Endogonalean. Their analysis found that CENP-A is absent in all Mucorales and Umbelopsidales, but is present in Endogonalean and other fungal clades, suggesting that CENP-A was present in the last Mucoromycotina common ancestor but was lost in the common ancestor of Mucorales and Umbelopsidales. Interestingly, CENP-C, a binding partner of CENP-A, was also lost in Mucorales. Loss of both CENP-A and CENP-C is found in certain insects, which in all known cases is associated with a transition to holocentricity [6]. To reveal what kind of centromere is present in Mucorales, the authors had a closer look into the fungi. Although it is often difficult to work on early-diverging fungi, a good amount of molecular tools is available in Mucor circinelloides [12], so they decided to examine this pathogenic
R1184 Current Biology 29, R1174–R1198, November 18, 2019 ª 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Current Biology
Dispatches Mucorales. They first tagged three kinetochore proteins (Mis12, Dsn1, and CENP-T) with fluorescent tags and found multiple punctate signals in the nucleus, suggesting that this organism has monocentric, rather than holocentric, chromosomes, despite the absence of CENP-A and CENP-C. To map the position of centromeres, they performed chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) for two kinetochore proteins (Mis12 and Dsn1). Nine peaks were observed by this approach, each having a major and minor signal. As expected, only one peak was found per chromosome, strongly suggesting that the peak corresponds to the core centromere where kinetochore proteins bind (Figure 1). The average length of the core centromeres is 1 kb, which are surrounded by gene-free pericentric regions (15 to 75 kb), where transposable elements are present (Figure 1). The sequence analysis revealed that these retrotransposons belong to the LINE1 clade, so the authors termed them genomic retrotransposable element of Mucoromycotina (Grem) LINE1. GremLINE1s are found specifically in the pericentric regions in Mucor circinelloides, often orienting away from the core centromeres. These elements therefore form large inverted repeats, a feature also found in some eukaryotes [13,14]. Interestingly, Grem-like elements are present in other Mucorales and Umbelopsidales (organisms without CENP-A), but not in Endogonalean (organisms with CENP-A), suggesting that Grem-LINE1s might play an important role in CENP-A-less Mucoromycotina. Transposable elements are present at centromeres in various species [15], while RNAi machinery is important for controlling the mobility of transposable elements and maintaining centromere structure and stability [16]. Mucor circinelloides has an elaborate RNAi system that protects its genome against invading elements or movement of transposable elements [17]. Indeed, the authors found that the Grem-LINE1s in the pericentric regions are silenced by the Dicer-dependent RNAi machinery. It will be important to test whether the RNAi machinery or Grem-LINE1s influence centromere functions in Mucor circinelloides.
CEN 4
Chromosome 4
Major signal Minor signal Kinetochore protein ChIP
Pericentric region Core Grem-LINE1 Grem-LINE1
Pericentric region
Grem-LINE1 Grem-LINE1 Grem-LINE1
Centromere-specific 41-bp sequence motif AT-rich Major peak
Centromere (~30 kb) Core centromere region (~1 kb)
Minor peak Current Biology
Figure 1. Mucor circinelloides centromere is a mosaic of point and regional centromere qualities. Schematic of the centromere region of chromosome 4 is shown. ChIP-seq of kinetochore proteins shows a single peak (major and minor signal) that marks the 1 kb core centromere region, which is surrounded by 30 kb pericentric regions that harbour Grem-LINE1 transposable elements. The core centromere has a centromere-specific 41-bp sequence motif and a highly AT-rich sequence stretch.
It is clear from these results that the centromere of this organism is regional despite the absence of CENP-A, but a further surprise was hidden in its sequence. So far, the only known specific DNA sequence present in the core centromere region is in budding yeasts that have point centromeres [5,18]. It was therefore unexpected that the authors identified a 41-bp unique DNA sequence motif that is present in all nine core centromeres, but is absent from any other chromosomal region. They also noticed that the minor signal of kinetochore proteins in the core centromere region was spaced by a highly AT-rich stretch followed by the major signal that starts with the 41-bp motif (Figure 1). Although the significance of the major and minor signals remains unclear, the major signal likely reflects a binding site for some kinetochore proteins that may directly bind the 41-bp motif. The presence of a unique sequence in Mucor circinelloides means that its centromere is a mosaic of point and regional centromeres, which represents an exciting discovery in centromere biology. It is thought that geneticallydefined centromeres are prone to exploitation by selfish DNA that hijacks the host segregation machinery (e.g., 2-micron plasmid in S. cerevisiae [19]). Although it remains unknown whether the centromere of Mucor circinelloides is genetically or epigenetically defined, it will be interesting to reveal the advantage or
disadvantage of having specific DNA sequence at centromeres. There are now at least three distinct groups of eukaryotes that lack CENP-A: certain insect lineages, Mucorales, and kinetoplastids. While it remains controversial whether kinetoplastids that have unconventional kinetochore proteins ancestrally possessed CENP-A or not [7,20], those insects and Mucorales that have otherwise canonical kinetochore components most likely lost CENP-A [6,11]. Why did those insects acquire holocentricity, while Mucor circinelloides remains monocentric? What kind of changes in kinetochore compositions happened immediately after the loss of CENP-A in these organisms? Furthermore, what is the advantage of having CENP-A or not having CENP-A? Although it is well known that centromeres in many species are relatively AT-rich, its significance remains unclear. It is noteworthy that the ATrichness at centromeres is also found in Mucor circinelloides and Trypanosoma brucei, species that do not have CENP-A but have functional RNAi machinery, suggesting that factors such as production of non-coding RNA might have something to do with the ATrichness. Finally, it is important to mention that understanding the biology of this pathogenic fungus has medical relevance. It is possible that there is a unique kinetochore protein that binds the 41-bp motif, which could represent a target. In any case, understanding the
Current Biology 29, R1174–R1198, November 18, 2019 R1185
Current Biology
Dispatches kinetochore in Mucor circinelloides will lead to important insights into the mechanism of kinetochore specification and assembly.
8. van Hooff, J.J., Tromer, E., van Wijk, L.M., Snel, B., and Kops, G.J. (2017). Evolutionary dynamics of the kinetochore network in eukaryotes as revealed by comparative genomics. EMBO Rep. 18, 1559–1571.
REFERENCES
9. Obado, S.O., Bot, C., Nilsson, D., Andersson, B., and Kelly, J.M. (2007). Repetitive DNA is associated with centromeric domains in Trypanosoma brucei but not Trypanosoma cruzi. Genome Biol. 8, R37.
1. Musacchio, A., and Desai, A. (2017). A molecular view of kinetochore assembly and function. Biology 6, https://doi.org/10.3390/ biology6010005. 2. Henikoff, S., Ahmad, K., and Malik, H.S. (2001). The centromere paradox: stable inheritance with rapidly evolving DNA. Science 293, 1098–1102. 3. Cleveland, D.W., Mao, Y., and Sullivan, K.F. (2003). Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 112, 407–421. trovic , N., and Mravinac, B. 4. Plohl, M., Mes (2014). Centromere identity from the DNA point of view. Chromosoma 123, 313–325. 5. Clarke, L., and Carbon, J. (1980). Isolation of a yeast centromere and construction of functional small circular chromosomes. Nature 287, 504–509. 6. Drinnenberg, I.A., deYoung, D., Henikoff, S., and Malik, H.S. (2014). Recurrent loss of CenH3 is associated with independent transitions to holocentricity in insects. Elife 3, e03676. 7. Akiyoshi, B., and Gull, K. (2014). Discovery of unconventional kinetochores in kinetoplastids. Cell 156, 1247–1258.
10. Garcia-Silva, M.-R., Sollelis, L., MacPherson, C.R., Stanojcic, S., Kuk, N., Crobu, L., Bringaud, F., Bastien, P., Page`s, M., Scherf, A., et al. (2017). Identification of the centromeres of Leishmania major: revealing the hidden pieces. EMBO Rep. 18, 1968–1977. 11. Navarro-Mendoza, M.-I., Perez-Arques, C., Panchal, S., Nicolas, F.E., Mondo, S.J., Ganguly, P., Pangilinan, J., Grigoriev, I.V., Heitman, J., Sanyal, K., and Garre, V. (2019). Early diverging fungus Mucor circinelloides lacks centromeric histone CENP-A and displays a mosaic of point and regional centromeres. Curr. Biol. 29, 3791–3802.
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Plant Biology: To Live, or Not to Live, That Is the Question Alice Y. Cheung Department of Biochemistry and Molecular Biology, Molecular and Cell Biology Program, Plant Biology Program, University of Massachusetts, Amherst, MA, USA Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.09.057
Organisms tread a fine line in balancing the decision to maintain cellular homeostasis or promote cell death to allow for renewal during development or halt the spread of a life-threatening crisis. Recent studies suggest a labyrinth of receptor kinase–cyclic nucleotide-gated ion channel connections mediates life-and-death decisions in plants. Triggering cell death is a strategy crucial for organisms to maintain life and survive in times of encountering challenges that threaten their well-being. In plants, cell death underlies important developmental
processes, such as the differentiation of the vascular system, development of root system architecture, sex differentiation, and production of fertile reproductive cells [1]. Local cell death is also crucial in
containing the damage incurred by pathogens at their invasion sites to prevent systemic spreading of diseases. Mechanistic understanding of how cell death is regulated in plants remains sparse.
R1186 Current Biology 29, R1174–R1198, November 18, 2019 ª 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).