Physical Laws shape up HOX Gene Collinearity

Hox gene collinearity (HGC) is a multiscalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC) where the Hox genes are located in the order (Hox1, Hox2, Hox3 …) along the 3’ to 5’ direction of DNA in the genome and a corresponding sequence of ontogenetic units (E1, E2, E3, …) located along the Anterior – Posterior axis of the embyo. Expression of Hox1 occurs in E1. Hox2 in E2, Hox3 in E3… Besides SC, a temporal collinearity (TC) has been also observed in many vertebrates. According to TC first is Hox1 expressed in E1, later is Hox2 expressed in E2, followed by Hox3 in E3,… Lately doubt has been raised whether TC really exists. A biophysical model (BM) was formulated and tested during the last twenty years. According to BM, physical forces are created which pull the Hox genes one after the other driving them to a transcription factory domain where they are transcribed. The existing experiments support this BM description. Symmetry is a physical-mathematical property of Matter that was explored in depth by Noether who formulated a ground-breaking theory that applies to all sizes of Matter. This theory applied to Biology can explain the origin of HGC as applied not only to animals developing along the A/P axis but also to animals with circular symmetry.

Physical Laws shape up HOX Gene Collinearity

10.20944/preprints202103.0450.v2 ◽

2021 ◽

Author(s):

Spyros Papageorgiou

Keyword(s):

Hox Genes ◽

Biophysical Model ◽

Mathematical Property ◽

Hox Gene ◽

Embryonic Tissues ◽

Transcription Factory ◽

Animal Phyla ◽

Physical Forces ◽

Physical Laws ◽

Physical Laws Shape Up HOX Gene Collinearity

Journal of Developmental Biology ◽

10.3390/jdb9020017 ◽

2021 ◽

Vol 9 (2) ◽

pp. 17

Author(s):

Spyros Papageorgiou

Keyword(s):

Hox Genes ◽

Biophysical Model ◽

Scalar Property ◽

Hox Gene ◽

Embryonic Tissues ◽

Transcription Factory ◽

Animal Phyla ◽

Physical Forces ◽

Physical Laws ◽

Hox gene collinearity (HGC) is a multi-scalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC), where the Hox genes are located in the order (Hox1, Hox2, Hox3 …) along the 3′ to 5′ direction of DNA in the genome and a corresponding sequence of ontogenetic units (E1, E2, E3, …) located along the Anterior—Posterior axis of the embryo. Expression of Hox1 occurs in E1, Hox2 in E2, Hox3 in E3, etc. Besides SC, a temporal collinearity (TC) has been also observed in many vertebrates. According to TC, first Hox1 is expressed in E1; later, Hox2 is expressed in E2, followed by Hox3 in E3, etc. Lately, doubt has been raised about whether TC really exists. A biophysical model (BM) was formulated and tested during the last 20 years. According to BM, physical forces are created which pull the Hox genes one after the other, driving them to a transcription factory domain where they are transcribed. The existing experimental data support this BM description. Symmetry is a physical–mathematical property of matter that was explored in depth by Noether who formulated a ground-breaking theory (NT) that applies to all sizes of matter. NT may be applied to biology in order to explain the origin of HGC in animals developing not only along the A/P axis, but also to animals with circular symmetry.

Recent Experiments Raised Doubt On the Vertebrate Temporal Collinearity of the Hox Genes. A Biophysical Model May Reconcile the Conflicting Findings

10.20944/preprints202012.0753.v2 ◽

2021 ◽

Author(s):

Spyros Papageorgiou

Keyword(s):

Dna Sequence ◽

Hox Genes ◽

The Other ◽

Biophysical Model ◽

Hox Gene ◽

Embryonic Tissues ◽

Transcription Factory ◽

Animal Phyla ◽

Physical Forces ◽

Hox gene collinearity (HGC) is a multiscalar property of many animal phyla particularly important during embryogenesis. It relates events occurring in Hox clusters inside the chromosome DNA and embryonic tissues. These two entities differ in size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC) where the Hox genes are located in the order H1, H2, H3 … along the 3’ to 5’ direction of the DNA sequence. The corresponding embryonic tissues (E1, E2, E3, …) are activated along the Anterior – Posterior axis in the same order. Besides this collinearity a temporal collinearity (TC) has been also observed in many vertebrates. According to TC first is H1 expressed in E1, later is H2 in E2, followed by H3,… Lately doubt has been raised whether TC really exists. A biophysical model (BM) has been formulated and tested in the last twenty years. According to BM, physical forces are created which pull the Hox genes one after the other driving them to a transcription factory domain where they are transcribed. The existing experiments support this BM description. In the present work two equivalent realizations of BM are presented which explain the recent findings on TC as observed in the vertebrates.

Hox Gene Collinearity May Be Related to Noether Theory on Symmetry and Its Linked Conserved Quantity

J ◽

10.3390/j3020013 ◽

2020 ◽

Vol 3 (2) ◽

pp. 151-161

Author(s):

Spyros Papageorgiou

Keyword(s):

Hox Genes ◽

Fundamental Property ◽

Gene Clusters ◽

Strand Break ◽

Early Embryo ◽

Conserved Quantity ◽

Biophysical Model ◽

Self Similarity ◽

Hox Gene ◽

Hox Gene Collinearity (HGC) is a fundamental property that controls the development of many animal species, including vertebrates. In the Hox gene clusters, the genes are located in a sequential order Hox1, Hox2, Hox3, etc., along the 3’ to 5’ direction of the cluster in the chromosome. During Hox cluster activation, the Hox genes are expressed sequentially in the ontogenetic units D1, D2, D3, etc., along the anterior–posterior axis (A-P) of the early embryo. This collinearity, first observed by E.B. Lewis, is surprising because the spatial collinearity of these structures (Hox clusters and embryos) correlates entities that differ by about four orders of magnitude. Biomolecular mechanisms alone cannot explain such correlations. Long-range physical interactions, such as diffusion or electric attractions, should be involved. A biophysical model (BM) was formulated, which, in alignment with the biomolecular processes, successfully describes the existing vertebrate genetic engineering data. One hundred years ago, Emmy Noether made a fundamental discovery in mathematics and physics. She proved, rigorously, that a physical system obeying a symmetry law (e.g., rotations or self-similarity) is followed by a conserved physical quantity. It is argued here that HGC obeys a ‘primitive’ self-similarity symmetry. In this case, the associated primitive conserved quantity is the irreversibly increasing ‘ratchet’-like Hoxgene ordering where some genes may be missing. The genes of a vertebrate Hox clusterare located along a finite straight line. The same order follows the ontogenetic unitsof the vertebrate embryo. Therefore, HGC is a manifestation of a primitive Noether Theory (NT). NT may be applied to other than the vertebrate case, for instance, to animals with a circular topological symmetry. For example, the observed abnormal Hox gene ordering of the echinoderm Hox clusters may be reproduced by a double-strand break of the circular Hox gene ordering and its subsequent incorporation in the flanking chromosome.

Disappearance of Temporal Collinearity in Vertebrates and Its Eventual Reappearance

Biology ◽

10.3390/biology10101018 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1018

Author(s):

Spyros Papageorgiou

Keyword(s):

Chromatin Immunoprecipitation ◽

Hox Genes ◽

Mouse Embryos ◽

Limb Bud ◽

Biophysical Model ◽

Embryonic Cells ◽

Hox Gene ◽

Mutant Cells ◽

Hox Clusters ◽

Chip Chip

In 1999 T. Kondo and D. Duboule performed excisions of posterior upstream DNA domains in mouse embryos and they observed that for an extended excision (including Evx gene) the Hox genes of the cluster were simultaneously expressed with the first Hoxd1 gene ‘as if’ Temporal Collinearity (TC) had disappeared. According to a Biophysical Model (BM) during Hox gene expression, Hox clusters behave similar toexpanding elastic springs. For the extended upstream DNA excision, BM predicts the TC disappearance and an experiment is proposed to test this BM prediction. In the chick limb bud C. Tickle et al. observed that the excision of the apical ectodermal ridge (AER) caused the inhibition of HoxA13 expression. However, the implantation of FGF soaked beads at the tip of the limb could surprisingly rescue HoxA13 expression after 24 hours so that TC is restored.Brachyury transcription factor (TF) is essential in identifying the targets of this transcription and a chromatin immunoprecipitation microarray chip (ChIP-chip) was produced which can be inserted in the mouse embryonic cells. It is here proposed to insert this chip in the mutant cells where TC has disappeared and compare it to the limb bud case.Is TC restored? It is an important issue worth exploring.

Hox genes are essential for the development of eyespots in Bicyclus anynana butterflies

Genetics ◽

10.1093/genetics/iyaa005 ◽

2020 ◽

Vol 217 (1) ◽

Author(s):

Yuji Matsuoka ◽

Antónia Monteiro

Keyword(s):

Hox Genes ◽

Bicyclus Anynana ◽

Hox Gene ◽

Novel Traits ◽

Anterior Posterior ◽

Anterior Posterior Axis

Abstract The eyespot patterns found on the wings of nymphalid butterflies are novel traits that originated first in hindwings and subsequently in forewings, suggesting that eyespot development might be dependent on Hox genes. Hindwings differ from forewings in the expression of Ultrabithorax (Ubx), but the function of this Hox gene in eyespot development as well as that of another Hox gene Antennapedia (Antp), expressed specifically in eyespots centers on both wings, are still unclear. We used CRISPR-Cas9 to target both genes in Bicyclus anynana butterflies. We show that Antp is essential for eyespot development on the forewings and for the differentiation of white centers and larger eyespots on hindwings, whereas Ubx is essential not only for the development of at least some hindwing eyespots but also for repressing the size of other eyespots. Additionally, Antp is essential for the development of silver scales in male wings. In summary, Antp and Ubx, in addition to their conserved roles in modifying serially homologous segments along the anterior–posterior axis of insects, have acquired a novel role in promoting the development of a new set of serial homologs, the eyespot patterns, in both forewings (Antp) and hindwings (Antp and Ubx) of B. anynana butterflies. We propose that the peculiar pattern of eyespot origins on hindwings first, followed by forewings, could be due to an initial co-option of Ubx into eyespot development followed by a later, partially redundant, co-option of Antp into the same network.

Gene loss and gain in the evolution of the vertebrates

Development ◽

10.1242/dev.1994.supplement.155 ◽

1994 ◽

Vol 1994 (Supplement) ◽

pp. 155-161

Author(s):

Frank H. Ruddle ◽

Kevin L. Bentley ◽

Michael T. Murtha ◽

Neil Risch

Keyword(s):

Hox Genes ◽

Gene Loss ◽

Biological Function ◽

Hox Gene ◽

Step Process ◽

Gene Expansion ◽

Multiple Clusters ◽

Adaptive Role ◽

Homeobox cluster genes (Hox genes) are highly conserved and can be usefully employed to study phyletic relationships and the process of evolution itself. A phylogenetic survey of Hox genes shows an increase in gene number in some more recently evolved forms, particularly in vertebrates. The gene increase has occurred through a two-step process involving first, gene expansion to form a cluster, and second, cluster duplication to form multiple clusters. We also describe data that suggests that non-Hox genes may be preferrentially associated with the Hox clusters and raise the possibility that this association may have an adaptive biological function. Hox gene loss may also play a role in evolution. Hox gene loss is well substantiated in the vertebrates, and we identify additional possible instances of gene loss in the echinoderms and urochordates based on PCR surveys. We point out the possible adaptive role of gene loss in evolution, and urge the extension of gene mapping studies to relevant species as a means of its substantiation.

Hox genes regulate asexual reproductive behavior and tissue segmentation in adult animals

Nature Communications ◽

10.1038/s41467-021-26986-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Christopher P. Arnold ◽

Analí Migueles Lozano ◽

Frederick G. Mann ◽

Stephanie H. Nowotarski ◽

Julianna O. Haug ◽

...

Keyword(s):

Asexual Reproduction ◽

Hox Genes ◽

Adult Stage ◽

Tissue Segmentation ◽

Hox Gene ◽

Downstream Effector ◽

Effector Genes ◽

And Behavior ◽

Insight Into ◽

AbstractHox genes are highly conserved transcription factors renowned for their roles in the segmental patterning of the embryonic anterior-posterior (A/P) axis. We report functions for Hox genes in A/P tissue segmentation and transverse fission behavior underlying asexual reproduction in adult planarian flatworms, Schmidtea mediterranea. Silencing of each of the Hox family members identifies 5 Hox genes required for asexual reproduction. Among these, silencing of hox3 genes results in supernumerary fission segments, while silencing of post2b eliminates segmentation altogether. The opposing roles of hox3 and post2b in segmentation are paralleled in their respective regulation of fission behavior. Silencing of hox3 increases the frequency of fission behavior initiation while silencing of post2b eliminates fission behavior entirely. Furthermore, we identify a network of downstream effector genes mediating Hox gene functions, providing insight into their respective mechanisms of action. In particular, we resolve roles for post2b and effector genes in the functions of the marginal adhesive organ in fission behavior regulation. Collectively, our study establishes adult stage roles for Hox genes in the regulation of tissue segmentation and behavior associated with asexual reproduction.

Staggered Hox expression is more widespread among molluscs than previously appreciated

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2018.1513 ◽

2018 ◽

Vol 285 (1888) ◽

pp. 20181513 ◽

Cited By ~ 8

Author(s):

Tim Wollesen ◽

Sonia Victoria Rodríguez Monje ◽

André Luiz de Oliveira ◽

Andreas Wanninger

Keyword(s):

Gene Expression ◽

Morphological Traits ◽

Hox Genes ◽

Developmental Stages ◽

Early Stage ◽

Genomic Data ◽

Published Data ◽

Hox Gene ◽

The Central Nervous System ◽

Hox genes are expressed along the anterior–posterior body axis in a colinear fashion in the majority of bilaterians. Contrary to polyplacophorans, a group of aculiferan molluscs with conserved ancestral molluscan features, gastropods and cephalopods deviate from this pattern by expressing Hox genes in distinct morphological structures and not in a staggered fashion. Among conchiferans, scaphopods exhibit many similarities with gastropods, cephalopods and bivalves, however, the molecular developmental underpinnings of these similar traits remain unknown. We investigated Hox gene expression in developmental stages of the scaphopod Antalis entalis to elucidate whether these genes are involved in patterning morphological traits shared by their kin conchiferans. Scaphopod Hox genes are predominantly expressed in the foot and mantle but also in the central nervous system. Surprisingly, the scaphopod mid-stage trochophore exhibits a near-to staggered expression of all nine Hox genes identified. Temporal colinearity was not found and early-stage and late-stage trochophores, as well as postmetamorphic individuals, do not show any apparent traces of staggered expression. In these stages, Hox genes are expressed in distinct morphological structures such as the cerebral and pedal ganglia and in the shell field of early-stage trochophores. Interestingly, a re-evaluation of previously published data on early-stage cephalopod embryos and of the gastropod pre-torsional veliger shows that these developmental stages exhibit traces of staggered Hox expression. Considering our results and all gene expression and genomic data available for molluscs as well as other bilaterians, we suggest a last common molluscan ancestor with colinear Hox expression in predominantly ectodermal tissues along the anterior–posterior axis. Subsequently, certain Hox genes have been co-opted into the patterning process of distinct structures (apical organ or prototroch) in conchiferans.

Dorsoventral dissociation of Hox gene expression underpins the diversification of molluscs

10.1101/603092 ◽

2019 ◽

Cited By ~ 2

Author(s):

Pin Huan ◽

Qian Wang ◽

Sujian Tan ◽

Baozhong Liu

Keyword(s):

Gene Expression ◽

Hox Genes ◽

Expression Patterns ◽

Ventral Side ◽

Shell Formation ◽

Dynamic Changes ◽

Hox Gene ◽

Expression Model ◽

Almost All ◽

AbstractUnlike the Hox genes in arthropods and vertebrates, those in molluscs show diverse expression patterns and, with some exceptions, have generally been described as lacking the canonical staggered pattern along the anterior-posterior (AP) axis. This difference is unexpected given that almost all molluscs share highly conserved early development. Here, we show that molluscan Hox expression can undergo dynamic changes, which may explain why previous research observed different expression patterns. Moreover, we reveal that a key character of molluscan Hox expression is that the dorsal and ventral expression is dissociated. We then deduce a generalized molluscan Hox expression model, including conserved staggered Hox expression in the neuroectoderm on the ventral side and lineage-specific dorsal expression that strongly correlates with shell formation. This generalized model clarifies a long-standing debate over whether molluscs possess staggered Hox expression and it can be used to explain the diversification of molluscs. In this scenario, the dorsoventral dissociation of Hox expression allows lineage-specific dorsal and ventral patterning in different clades, which may have permitted the evolution of diverse body plans in different molluscan clades.