Recurrent erosion of COA1/MITRAC15 exemplifies conditional gene dispensability in oxidative phosphorylation

Skeletal muscle fibers rely upon either oxidative phosphorylation or the glycolytic pathway with much less reliance on oxidative phosphorylation to achieve muscular contractions that power mechanical movements. Species with energy-intensive adaptive traits that require sudden bursts of energy have a greater dependency on glycolytic fibers. Glycolytic fibers have decreased reliance on OXPHOS and lower mitochondrial content compared to oxidative fibers. Hence, we hypothesized that gene loss might have occurred within the OXPHOS pathway in lineages that largely depend on glycolytic fibers. The protein encoded by the COA1/MITRAC15 gene with conserved orthologs found in budding yeast to humans promotes mitochondrial translation. We show that gene disrupting mutations have accumulated within the COA1 gene in the cheetah, several species of galliform birds, and rodents. The genomic region containing COA1 is a well-established evolutionary breakpoint region in mammals. Careful inspection of genome assemblies of closely related species of rodents and marsupials suggests two independent COA1 gene loss events co-occurring with chromosomal rearrangements. Besides recurrent gene loss events, we document changes in COA1 exon structure in primates and felids. The detailed evolutionary history presented in this study reveals the intricate link between skeletal muscle fiber composition and the occasional dispensability of the chaperone-like role of the COA1 gene.

Origin and evolutionary landscape of Nr2f transcription factors across Metazoa

Background Nuclear Receptor Subfamily 2 Group F (Nr2f) orphan nuclear hormone transcription factors (TFs) are fundamental regulators of many developmental processes in invertebrates and vertebrates. Despite the importance of these TFs throughout metazoan development, previous work has not clearly outlined their evolutionary history. Results We integrated molecular phylogeny with comparisons of intron/exon structure, domain architecture, and syntenic conservation to define critical evolutionary events that distinguish the Nr2f gene family in Metazoa. Our data indicate that a single ancestral eumetazoan Nr2f gene predated six main Bilateria subfamilies, which include single Nr2f homologs, here referred to as Nr2f1/2/5/6, that are present in invertebrate protostomes and deuterostomes, Nr2f1/2 homologs in agnathans, and Nr2f1, Nr2f2, Nr2f5, and Nr2f6 orthologs that are found in gnathostomes. Four cnidarian Nr2f1/2/5/6 and three agnathan Nr2f1/2 members are each due to independent expansions, while the vertebrate Nr2f1/Nr2f2 and Nr2f5/Nr2f6 members each form paralogous groups that arose from the established series of whole-genome duplications (WGDs). Nr2f6 members are the most divergent Nr2f subfamily in gnathostomes. Interestingly, in contrast to the other gnathostome Nr2f subfamilies, Nr2f5 has been independently lost in numerous vertebrate lineages. Furthermore, our analysis shows there are differential expansions and losses of Nr2f genes in teleosts following their additional rounds of WGDs. Conclusion Overall, our analysis of Nr2f gene evolution helps to reveal the origins and previously unrecognized relationships of this ancient TF family, which may allow for greater insights into the conservation of Nr2f functions that shape Metazoan body plans.

Internally Symmetrical Stwintrons and Related Canonical Introns in Hypoxylaceae Species

Spliceosomal introns are pervasive in eukaryotes. Intron gains and losses have occurred throughout evolution, but the origin of new introns is unclear. Stwintrons are complex intervening sequences where one of the sequence elements (5′-donor, lariat branch point element or 3′-acceptor) necessary for excision of a U2 intron (external intron) is itself interrupted by a second (internal) U2 intron. In Hypoxylaceae, a family of endophytic fungi, we uncovered scores of donor-disrupted stwintrons with striking sequence similarity among themselves and also with canonical introns. Intron–exon structure comparisons suggest that these stwintrons have proliferated within diverging taxa but also give rise to proliferating canonical introns in some genomes. The proliferated (stw)introns have integrated seamlessly at novel gene positions. The recently proliferated (stw)introns appear to originate from a conserved ancestral stwintron characterised by terminal inverted repeats (45–55 nucleotides), a highly symmetrical structure that may allow the formation of a double-stranded intron RNA molecule. No short tandem duplications flank the putatively inserted intervening sequences, which excludes a DNA transposition-based mechanism of proliferation. It is tempting to suggest that this highly symmetrical structure may have a role in intron proliferation by (an)other mechanism(s).

Origin and evolutionary landscape of Nr2f transcription factors across Metazoa

Background: Nuclear Receptor Subfamily 2 Group F (Nr2f) orphan nuclear hormone transcription factors (TFs) are fundamental regulators of many developmental processes in invertebrates and vertebrates. Despite the importance of these TFs throughout metazoan development, previous work has not clearly outlined their evolutionary history. Results: We integrated molecular phylogeny with comparisons of intron/exon structure, domain architecture, and syntenic conservation to define critical evolutionary events that distinguish the Nr2f gene family in Metazoa. Our data indicate that a single ancestral pre-metazoan Nr2f gene, we have termed Nr2f1/2/5/6, predated six main Bilateria subfamilies, which include a single Nr2f1/2/5 homolog that is present throughout protostomes and invertebrate deuterostomes, Nr2f1/2 homologs in agnathans, and Nr2f1 , Nr2f2 , Nr2f5 , Nr2f6 orthologs that are found in gnathostomes. The three Nr2f1/2 members in agnathans are due to independent expansions not found in gnathostomes, while the vertebrate Nr2f1 , Nr2f2 , Nr2f5 members arose from whole-genome duplications (WGDs). However, Nr2f6 members are the most divergent subfamily, likely originating from an ancient duplication, and are only retained by gnathostomes. Interestingly, Nr2f5 TFs have been independently lost in both cartilaginous fish and amniotes, such as humans. Furthermore, our analysis shows there are differential expansions and losses of Nr2f genes in teleosts following their additional rounds of WGDs. Conclusion: Overall, our evolutionary genomic analysis of Nr2f proteins helps to reveal the origins and previously unrecognized relationships of this ancient transcription factor family, which may allow for greater insights into the conservation of Nr2f functions that shape Metazoan body plans.

Revised Exon Structure of l-DOPA Decarboxylase (DDC) Reveals Novel Splice Variants Associated with Colorectal Cancer Progression

Colorectal cancer (CRC) is a highly heterogenous malignancy with an increased mortality rate. Aberrant splicing is a typical characteristic of CRC, and several studies support the prognostic value of particular transcripts in this malignancy. l-DOPA decarboxylase (DDC) and its derivative neurotransmitters play a multifaceted role in physiological and pathological states. Our recent data support the existence of 6 DDC novel exons. In this study, we investigated the existence of additional DDC novel exons and transcripts, and their potential value as biomarkers in CRC. Next-generation sequencing (NGS) in 55 human cell lines coupled with Sanger sequencing uncovered 3 additional DDC novel exons and 20 splice variants, 7 of which likely encode new protein isoforms. Eight of these transcripts were detected in CRC. An in-house qPCR assay was developed and performed in TNM II and III CRC samples for the quantification of transcripts bearing novel exons. Extensive biostatistical analysis uncovered the prognostic value of specific DDC novel exons for patients’ disease-free and overall survival. The revised DDC exon structure, the putative protein isoforms with distinct functions, and the prognostic value of novel exons highlight the pivotal role of DDC in CRC progression, indicating its potential utility as a molecular biomarker in CRC.

Genome Wide Identification and Characters of TCP Family Genes in Brassica juncea var. tumida

Background Teosinte branched1/Cycloidea/Proliferating cell factor (TCP) proteins are plant-specific transcription factors, which widely involved in leaf development, flowering, shoot branching, and circadian rhythm. So far, TCP proteins function in tumorous stem mustard has not been reported. . Here we identified and characterized the entire TCP protein family members in the tumorous stem mustard. Results We identified fifty-four TCP genes in Brassica juncea var. tumida, containing thirty-three Class I subfamily members and twenty-one Class II subfamily members. Fifty-three TCP genes are distributed on 15 chromosomes. Gene structure and conserved motif analysis showed that the same clade genes have similar gene intron/exon structure and conserved motifs. Cis-acting element results showed that the same clade genes also have similar cis-element, however subtle differences also imply the different regulated pathway. More than twice paralogs genes relation to diploid species in some members imply gene duplication events in evolution. The members of BjTCP18s are low expressed in DY strains and un-swelling stage of YA strains. After treatment with GA and SA, it was detected that the expression levels of multiple TCP genes were affected by these two hormones. Conclusion In this study, we perform the first genome-wide analysis of the tumorous stem mustard TCP gene family. The results provide valuable information for understanding the classification and functions of TCP genes in tumorous stem mustard.

SITEX 2.0: Projections of protein functional sites on eukaryotic genes. Extension with orthologous genes

Functional sites define the diversity of protein functions and are the central object of research of the structural and functional organization of proteins. The mechanisms underlying protein functional sites emergence and their variability during evolution are distinguished by duplication, shuffling, insertion and deletion of the exons in genes. The study of the correlation between a site structure and exon structure serves as the basis for the in-depth understanding of sites organization. In this regard, the development of programming resources that allow the realization of the mutual projection of exon structure of genes and primary and tertiary structures of encoded proteins is still the actual problem. Previously, we developed the SitEx system that provides information about protein and gene sequences with mapped exon borders and protein functional sites amino acid positions. The database included information on proteins with known 3D structure. However, data with respect to orthologs was not available. Therefore, we added the projection of sites positions to the exon structures of orthologs in SitEx 2.0. We implemented a search through database using site conservation variability and site discontinuity through exon structure. Inclusion of the information on orthologs allowed to expand the possibilities of SitEx usage for solving problems regarding the analysis of the structural and functional organization of proteins. Database URL: http://www-bionet.sscc.ru/sitex/ .