Germline

In biology and genetics , the germline is a population of cells of a multicellular organism that pass their genetic material to progeny ( offspring ). In other words, they are the cells that make up the egg , the sperm , and the fertilized egg . They are usually differentiated to perform this function and dissociate at a specific location away from other bodily cells.

Germline
Germline

As a rule, this infection occurs through the process of sexual reproduction ; Generally it is a process that involves systematic changes in genetic material, changes that occur during recombination , for example in meiosis and fertilization . However, there are many exceptions across multicellular organisms, including various forms of processes and concepts such as apomixis , autogamy , automixis , cloning or parthenogenesis . [2] [3] Germline cells are commonly called germ cells . [4]For example, gametes such as sperm or egg are part of the germline. So the cells that divide are producing gametes, called gametes , cells that produce those, called gametogonia , and all the way back to the zygote , the cell, which developed separately.

In sexually reproducing organisms, cells that are not present in the germline are called somatic cells . According to this view, mutations , recombination, and other genetic changes in the germline can be passed on to the offspring, but transformation into a somatic cell will not. [5] This need not apply to somatically reproducing organisms such as some Porifera [6] and many plants. For example, many varieties of Citrus , [7] in plants such as Rosaceae and some in Asteraceae , such as Taraxacum yield seeds apomictically when somatic diploidThe cells migrate to the spore or early embryo.

At an earlier stage of genetic thinking, the distinction between germline and somatic cells was clear. For example, August Weisman proposed and explained, a germline cell is immortal in the sense that it is part of a lineage that has reproduced indefinitely from the beginning of life and does so indefinitely, except by accident. can continue. [9] However, it is now known in some detail that this distinction between somatic and germ cells is partly artificial and that special conditions and internal cellular mechanisms such as telomeres control and control the selective application of telomerase in germ cells, stem cells . Depends on and .

Not all multicellular organisms differentiate into somatic and germ lines, [11] but in the absence of specialized technological human intervention, practically all simple multicellular structures do. Somatic cells in such organisms are practically completely capable, and for more than a century, sponge cells have been known to reassemble into new sponges after being separated through a sieve.

Germline may refer to a lineage of cells spanning several generations of individuals—for example, the germline that links any living individual to the hypothetical last universal common ancestor from which all plants and animals descend.

Continuous improvement

Plants and basal metazoans such as sponges (Porifera) and corals (Anthozoa) do not sequester a distinct germline, producing gametes from the multipotent stem cell lineage that also gives rise to normal somatic tissues. It is therefore likely that germline sequestration first evolved in complex animals with sophisticated body plans, that is, bilaterians. There are several theories on the origin of the strict germ-soma distinction. Separating a distinct germ cell population early in embryogenesis may promote cooperation between somatic cells of a complex multicellular organism. [12] Another recent theory suggests that early germline sequences evolved to limit the accumulation of deleterious mutations in mitochondrial genes in complex organisms with high energy requirements and rapid mitochondrial mutation rates.

DNA damage, mutation and repair

Reactive oxygen species (ROS) are produced as a byproduct of metabolism. In germline cells, ROS are probably an important cause of DNA damage, which leads to mutations upon DNA replication. 8-oxoguanine, an oxidized derivative of guanine, is produced by spontaneous oxidation in germline cells of mice, and GC to TA transversion mutations occur during the cell’s DNA replication. [13] Such mutations occur throughout the mouse chromosomes as well as during different stages of gametogenesis.

The mutation frequencies for cells at different stages of gametogenesis are approximately 5 to 10 times lower than for somatic cells for both spermatogenesis [14] and oogenesis. [15] The lower frequency of mutations in germline cells than in somatic cells appears to be due to more efficient DNA repair of DNA damage, particularly homologous recombination repair, in germline meiosis. In humans, about five percent of surviving offspring have a genetic disorder, and about 20% of these are due to newly generated germline mutations.

epigenetic changes

Epigenetic changes to DNA include modifications that affect gene expression, but are not caused by changes in the sequence of bases in DNA. A well-studied example of such a change is the methylation of DNA cytosines to form 5-methylcytosine. This usually occurs in the DNA sequence CpG, mutating the DNA at the CpG site from CpG to 5-mcpG. Methylation of cytosines in CpG sites in the promoter regions of genes can reduce or silence gene expression. [16] There are approximately 28 million CpG dinucleotides in the human genome, [17] and approximately 24 million CpG sites in the mouse genome (which is 86% larger than the human genome [18] ). In most tissues of mammals, on average 70% to 80% of CpGs are cytosine methylated (forming 5-mCpG).[19]

In the mouse, from 6.25 to 7.25 days after fertilization of the egg by the sperm, cells in the embryo are isolated as primordial germ cells (PGCs). These PGCs will later give rise to germline sperm cells or egg cells. At this point PGCs have high specific levels of methylation. The mouse’s primordial germ cells then undergo genome-wide DNA demethylation, followed by new methylation to reset the epigenome to form an egg or sperm.

In the mouse, PGCs undergo DNA demethylation in two stages. The first stage, starting at embryonic day 8.5, occurs during PGC proliferation and migration, and results in a genome-wide loss of methylation, which includes nearly all genomic sequences. This loss of methylation occurs through passive demethylation due to repression of key components of the methylation machinery. [20]The second stage occurs at embryonic days 9.5 to 13.5 and causes demethylation of most of the remaining specific loci, including germline-specific and meiosis-specific genes. This second step of demethylation is mediated by the TET enzymes TET1 and TET2, which perform the first step in demethylation by converting 5-mC to 5-hydroxymethylcytosine (5-hmC) during embryonic days 9.5 to 10.5 . This is followed by a replication-dependent dilution at embryonic days 11.5 to 13.5. [21] At embryonic day 13.5, PGCs exhibit the lowest level of global DNA methylation of all cells in the genome life cycle. [20]

In the mouse, PGCs are upregulated in both male and female PGCs from embryonic day 9.5 to 13.5, when most genes are demethylated. [21]

Following erasure of DNA methylation marks in mouse PGCs, male and female germ cells undergo new methylation at different time points during gametogenesis. The male germline begins the re-methylation process from embryonic day 14.5, undergoing mitotic expansion in the developing gonad. Sperm-specific methylation patterns are maintained during mitotic expansion. The level of DNA methylation in primary oocytes before birth remains low, and re-methylation occurs after birth in the oocyte developmental stage.