Reconstruction of human genome evolution in yeast: an educational primer for use with “systematic humanization of the yeast cytoskeleton discerns functionally replaceable from divergent human genes”

Genetics ◽  
2021 ◽  
Vol 219 (2) ◽  
Author(s):  
Zuzana Brzáčová ◽  
Mária Peťková ◽  
Katarína Veljačiková ◽  
Terézia Zajičková ◽  
Ľubomír Tomáška
Keyword(s):  
Protein Function ◽  
Gene Families ◽  
Genomic Databases ◽  
Human Genes ◽  
Lineage Specific Expansion ◽  
Human Genome Evolution ◽  
Specific Expansion ◽  
Methodological Approaches ◽  
Eukaryotic Organisms ◽  
Design Experiments

Abstract The evolution of eukaryotic organisms starting with the last eukaryotic common ancestor was accompanied by lineage-specific expansion of gene families. A paper by Garge et al. provides an excellent opportunity to have students explore how expansion of gene families via gene duplication results in protein specialization, in this case in the context of eukaryotic cytoskeletal organization . The authors tested hypotheses about conserved protein function by systematic “humanization” of the yeast cytoskeletal components while employing a wide variety of methodological approaches. We outline several exercises to promote students’ ability to explore the genomic databases, perform bioinformatic analyses, design experiments for functional analysis of human genes in yeast and critically interpret results to address both specific and general questions.

scholarly journals Systematic Humanization of the Yeast Cytoskeleton Discerns Functionally Replaceable from Divergent Human Genes

Genetics ◽  
2020 ◽  
Vol 215 (4) ◽  
pp. 1153-1169 ◽  
Author(s):  
Riddhiman K. Garge ◽  
Jon M. Laurent ◽  
Aashiq H. Kachroo ◽  
Edward M. Marcotte
Keyword(s):  
Gene Families ◽  
Growth Defect ◽  
Gene Duplications ◽  
Yeast Gene ◽  
Macromolecular Transport ◽  
Cellular Processes ◽  
Growth Defects ◽  
Yeast Strains ◽  
Human Genes ◽  
Interaction Partners

Many gene families have been expanded by gene duplications along the human lineage, relative to ancestral opisthokonts, but the extent to which the duplicated genes function similarly is understudied. Here, we focused on structural cytoskeletal genes involved in critical cellular processes, including chromosome segregation, macromolecular transport, and cell shape maintenance. To determine functional redundancy and divergence of duplicated human genes, we systematically humanized the yeast actin, myosin, tubulin, and septin genes, testing ∼81% of human cytoskeletal genes across seven gene families for their ability to complement a growth defect induced by inactivation or deletion of the corresponding yeast ortholog. In five of seven families—all but α-tubulin and light myosin, we found at least one human gene capable of complementing loss of the yeast gene. Despite rescuing growth defects, we observed differential abilities of human genes to rescue cell morphology, meiosis, and mating defects. By comparing phenotypes of humanized strains with deletion phenotypes of their interaction partners, we identify instances of human genes in the actin and septin families capable of carrying out essential functions, but failing to fully complement the cytoskeletal roles of their yeast orthologs, thus leading to abnormal cell morphologies. Overall, we show that duplicated human cytoskeletal genes appear to have diverged such that only a few human genes within each family are capable of replacing the essential roles of their yeast orthologs. The resulting yeast strains with humanized cytoskeletal components now provide surrogate platforms to characterize human genes in simplified eukaryotic contexts.

scholarly journals Arabidopsis MORC proteins function in the efficient establishment of RNA directed DNA methylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Xue ◽  
Zhenhui Zhong ◽  
C. Jake Harris ◽  
Javier Gallego-Bartolomé ◽  
Ming Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Arabidopsis Thaliana ◽  
Transposable Element ◽  
Zinc Finger ◽  
Protein Function ◽  
C Elegans ◽  
Eukaryotic Organisms

AbstractThe Microrchidia (MORC) family of ATPases are required for transposable element (TE) silencing and heterochromatin condensation in plants and animals, and C. elegans MORC-1 has been shown to topologically entrap and condense DNA. In Arabidopsis thaliana, mutation of MORCs has been shown to reactivate silent methylated genes and transposons and to decondense heterochromatic chromocenters, despite only minor changes in the maintenance of DNA methylation. Here we provide the first evidence localizing Arabidopsis MORC proteins to specific regions of chromatin and find that MORC4 and MORC7 are closely co-localized with sites of RNA-directed DNA methylation (RdDM). We further show that MORC7, when tethered to DNA by an artificial zinc finger, can facilitate the establishment of RdDM. Finally, we show that MORCs are required for the efficient RdDM mediated establishment of DNA methylation and silencing of a newly integrated FWA transgene, even though morc mutations have no effect on the maintenance of preexisting methylation at the endogenous FWA gene. We propose that MORCs function as a molecular tether in RdDM complexes to reinforce RdDM activity for methylation establishment. These findings have implications for MORC protein function in a variety of other eukaryotic organisms.

scholarly journals The diversification and lineage-specific expansion of nitric oxide signaling in Placozoa: insights in the evolution of gaseous transmission

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Leonid L. Moroz ◽  
Daria Y. Romanova ◽  
Mikhail A. Nikitin ◽  
Dosung Sohn ◽  
Andrea B. Kohn ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Signaling ◽  
Lineage Specific Expansion ◽  
Specific Expansion

scholarly journals Basic Helix-Loop-Helix (bHLH) Transcription Factors Regulate a Wide Range of Functions in Arabidopsis

2021 ◽  
Vol 22 (13) ◽  
pp. 7152
Author(s):  
Yaqi Hao ◽  
Xiumei Zong ◽  
Pan Ren ◽  
Yuqi Qian ◽  
Aigen Fu
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Target Genes ◽  
Gene Families ◽  
Bhlh Transcription Factor ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Wide Range ◽  
Range Of Functions ◽  
Eukaryotic Organisms

The basic helix-loop-helix (bHLH) transcription factor family is one of the largest transcription factor gene families in Arabidopsis thaliana, and contains a bHLH motif that is highly conserved throughout eukaryotic organisms. Members of this family have two conserved motifs, a basic DNA binding region and a helix-loop-helix (HLH) region. These proteins containing bHLH domain usually act as homo- or heterodimers to regulate the expression of their target genes, which are involved in many physiological processes and have a broad range of functions in biosynthesis, metabolism and transduction of plant hormones. Although there are a number of articles on different aspects to provide detailed information on this family in plants, an overall summary is not available. In this review, we summarize various aspects of related studies that provide an overview of insights into the pleiotropic regulatory roles of these transcription factors in plant growth and development, stress response, biochemical functions and the web of signaling networks. We then provide an overview of the functional profile of the bHLH family and the regulatory mechanisms of other proteins.

scholarly journals Lineage-specific expansion of the Zinc Finger Associated Domain ZAD

2007 ◽  
Vol 24 (9) ◽  
pp. 1934-1943 ◽  
Author(s):  
Ho-Ryun Chung ◽  
Ulrike Löhr ◽  
Herbert Jäckle
Keyword(s):  
Zinc Finger ◽  
Lineage Specific Expansion ◽  
Specific Expansion

scholarly journals Lineage-specific expansion of DNA-binding transcription factor families

2010 ◽  
Vol 26 (9) ◽  
pp. 388-393 ◽  
Author(s):  
Varodom Charoensawan ◽  
Derek Wilson ◽  
Sarah A. Teichmann
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Lineage Specific Expansion ◽  
Specific Expansion
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