The evolutionary history of histone H3 suggests a deep eukaryotic root of chromatin modifying mechanisms   2010

Evolution of the Drosophila melanogaster Chromatin Landscape and Its Associated Proteins   2019

The fifth and last chromatin type, BLACK, has not been addressed in this work. Even if it covers approximately half the genome, it is hard to interpret because it is mechanistically poorly understood and its proteins overlap strongly with those of BLUE chromatin.

To place these results in context, we discuss some critical points of our study. First of all, there is currently no complete list of proteins associated to chromatin.

Selecting only known proteins necessarily introduces a bias in the data set; these proteins may not uniformly address all chromatin-related dynamics.

biases remain due to potential experimental and technical issues. For instance, the genome scan may exclude bona fide CAPs due to the search criteria. Thus, one has to keep in mind that the evolutionary trends that we detect can be influenced by a bias in the data set. On a more philosophical note, the proteome used in this study is the current state of knowledge in the field, and as this body of work will be improved upon in the future, so will its interpretation.

we cannot exclude that even if sequences and domains are very similar, the exact role in chromatin organization may be different.

Finally, as with most proposals of a specific unfolding of the evolutionary process, we note that there is an element of speculation present.

Histone Modifications, Gene Regulation, and the Origins of Multicellularity

The evolution of (animal) multicellularity is one of the major transitions in evolution. Within the area of (epi)genomics, it has been hypothesized that complexification of chromatin states and in particular the emergence of distinct heterochromatin states lay at the origin of multicellular life

In summary, these studies propose that an elaboration of chromatin states is based on (unique) combinations of histone modifications.

we find diversification of histone marks and the accompanying proteins, and as mentioned earlier, that may allow for a more fine-grained regulatory control over the genome.

Taken together, we affirm the importance of regulatory complexification in the success of multicellular life. Like other studies, our work suggests this regulatory complexification to be linked with the need to control chromatin states and their propagation in an increasingly complex landscape of active and repressive genomic regions.

we need additional studies that focus on different cell types and other species to deepen and broaden that knowledge.

 For instance, we do not know how chromatin states differ in Drosophila over development and between tissues.

Comparing different species is crucial to determine if the evolutionary scenarios that we propose indeed hold true and how they may need to be refined or reconsidered. One future breakthrough we hope for, is that such studies could provide insight into new BLACK-associated proteins and perhaps lead to a better molecular and evolutionary characterization of this type.

we advocate for an inclusion of ncRNA functionality within the analyses on different chromatin states across species. Clearly, our current study is but an introduction that shows the potential exists for new insights into the evolution of the chromatin landscape.

Perhaps any claim that this paper seems to answer important questions could be taken as valid up to certain point, but note that the paper does not explain how the chromatin histone octamers originated or evolved.  It just describes their observations and obviously sprinkle the expected “evolutionary” jargon over the text just to make sure it’s acceptable to the censorship.

Let’s be aware that the biology research literature is huge and it keeps growing, but it’s mainly describing what they observe, answering outstanding questions while posing new ones. That seems the result of the reductionist bottom-up research approach that is generally taken, which seems like a reverse engineering work. Such a path usually generates more questions than it can answer. Specially when it deals with a complex system that was designed top-down.

Important issues raised here:

complexification of chromatin states

emergence of distinct heterochromatin states

combinations of histone modifications

diversification of histone marks and the accompanying proteins

more fine-grained regulatory control over the genome.

regulatory complexification

control chromatin states and their propagation in an increasingly complex landscape of active and repressive genomic regions.

ncRNA functionality

chromatin landscape

 

Non-neutral evolution of H3.3-encoding genes occurs without alterations in protein sequence

Histone H3.3 is a developmentally essential variant encoded by two independent genes in human (H3F3A and H3F3B). While this two-gene arrangement is evolutionarily conserved, its origins and function remain unknown.

We infer that H3F3B is more similar to the ancestral H3.3 gene and likely evolutionarily adapted for a broad expression pattern in diverse cellular programs, while H3F3A adapted for a subset of gene expression programs. Thus, the arrangement of two independent H3.3 genes facilitates fine-tuning of H3.3 expression across cellular programs.

In eukaryotic cells genomic DNA is packaged into chromatin, which plays a dual role of genome compaction and regulation. Basic repeating units of chromatin, called nucleosomes, comprise 147 bp of DNA wrapped around a core that is formed by histone proteins of four types (H2A, H2B, H3, and H4), which are conserved in eukaryotic organisms including animals, fungi and plants. The histones fall into two major types: replication-dependent (RD) canonical histones and replication-independent (RI) non-canonical variants. The RI histone variants have diverse biological roles and are part of the epigenetic regulation of genome function. Unlike the canonical histones that are encoded by co-regulated gene clusters (histone loci), RI variants are encoded by individual genes that are regulated similarly to other protein coding genes.

while H3F3A and H3F3B encode the same protein product, they are under different regulatory mechanisms and play distinct roles.

Evolution of H3.3 encoding genes was analyzed in Drosophila species; however, on a larger scale, the biological function and evolutionary history of such two-gene organization remains unclear, despite its biomedical significance

This observation of coding sequence optimization for distinct transcriptional programs provides insight into why both H3F3A and H3F3B have been maintained over the course of evolution, even though they encode an identical amino-acid sequence.

The H3.3 histone is currently a subject of intense research due to its biological and biomedical significance; however, evolution of the genes encoding this protein is not fully understood.

codon usage in H3F3B is similar to that of ‘cell differentiation-induced’ genes, in contrast to the codon usage in H3F3A, which is similar to that of ‘cell proliferation-induced genes’

H3F3A and H3F3B genes are evolutionary optimized for different transcriptional programs through codon usage preferences and intron-exon organization.

In summary, the H3.3 genes provide a unique ‘study case’, in which the protein sequence remains constant over the course of evolution for an extended time period, allowing analysis of the selection operating at nucleotide level. Such analysis reveals an evolutionary mechanism of nucleotide sequence optimization for the fine-tuning of gene expression in specific cellular programs. In this work we have not addressed the questions of possible differences in the regulation of mRNA transcription from each of the H3.3 genes or posttranslational modifications that histones produced from the individual genes may preferentially bear. Answering these questions would require additional studies and they will undoubtedly shed new light on the biomedical significance of the existence of independent H3.3 genes.