segunda-feira, 22 de junho de 2015

Nucleosomes and irreducible complexity



A nucleosome is a basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound in sequence around eight  histone protein cores. This structure is often compared to thread wrapped around a spool. The basic level of DNA compaction is the nucleosome, where the double helix is wrapped around the histone octamer containing two copies of each histone H2A, H2B, H3 and H4Linker histone H1 binds the DNA between nucleosomes and facilitates packaging of the 10 nm "beads on the string" nucleosomal chain into a more condensed 30 nm fiber.

Histones are among the most highly conserved eucaryotic proteins. For example, the amino acid sequence of histone H4 from a pea and from a cow differ at only 2 of the 102 positions. This strong evolutionary conservation suggests that the functions of histones involve nearly all of their amino acids, so that a change in any position is deleterious to the cell. This suggestion has been tested directly in yeast cells, in which it is possible to mutate a given histone gene in uitro andintroduce it into the yeast genome in place of the
normal gene. As might be expected, most changes in histone sequences are lethal; the few that are not lethal cause changes in the normal pattern of gene expression, as well as other abnormalities.


If a change in histone sequences are lethal, how could it probably come to be in gradual steps, or trial and error ? As long as the correct sequence is not reached, no function..... 

Nucleosome assembly following DNA replication, DNA repair and gene transcription is critical for the maintenance of genome stability and epigenetic information.

In assembling a nucleosome, the histone folds first bind to each other to form H3-H4 and H2A-H2B dimers, and the H3-H4 dimers combine to form tetramers. An H3-H4 tetramer then further combines with two HZA-H2B dimers to form the compact octamer core, around which the DNA is wound

The  assembly is a sequential  multistep process, requiring several  folds and steps in a highly organized, regulated and precise manner, and must have been programmed and functional right from the beginning. Histone chaperones play important roles in regulating the intricate steps involved in folding of histones together with DNA to form correctly assembled nucleosomes, furthermore  assembly, disassembly and histone exchange to facilitate DNA replication, repair and transcription. There is a need for histone chaperones to guide the process and each step along the assembly pathway is carefully controlled and regulated by these histone chaperones. It is evident that a stepwise evolutionary fashion of development of histone chaperones to guide the process would result in a disaster. They had to be there fully working and programmed to do their job right from the start.  
Furthermore, to add to the already amazing machine like performance,  (linker histones) have to participate at each step in the processes of nucleosome assembly, disassembly and histone exchange during different genomic processes.   Linker histone H1 is an essential component of chromatin structure ( so its irreducible ).  H1 links nucleosomes into higher order structures.


Nucleosome formation is dependent on the positive charges of the H4 histones and the negative charge on the surface of H2A histone fold domains. Acetylation of the histone tails disrupts this association, leading to weaker binding of the nucleosomal components. Histone acetyltransferases (HATs) and Histone deacetylase ( HDAC ) are also essential enzymes, that  remove through acetylation the  positive charge on the histones, and as a consequence, the condensed chromatin is transformed into a more relaxed structure that is associated with greater levels of gene transcription. This relaxation can be reversed by HDAC activity. 

So we can conclude that all these parts, DNA,  Linker histone H1, histones H2A, H2B, H3 and H4,and acetyltransferases (HATs) and Histone deacetylase ( HDAC ) form a  set of well-matched, mutually interacting, nonarbitrarily individuated parts such that each part in the set is indispensable to maintaining the system's basic, and therefore original, function.  The set of these indispensable parts is known as the irreducible core of the system, while Histone chaperones are also essential to build the since they guide the process and each step along the assembly pathway.

http://elshamah.heavenforum.org/t2051-nucleosomes-function-and-design#3524

Nenhum comentário:

Postar um comentário