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How Mysterious Songbird Chromosome May Help In Fight Against Cancer

Chromosomes Are Thread-like Structures Located Inside The Nucleus Of Animal And Plant Cells.

PTI | Updated on: 10 Dec 2019, 08:33:26 AM
The researchers of the current study sampled the genome of the songbird -- zebra finches -- and analysed a special chromosome called the Germline-restricted chromosome.

New Delhi:

Researchers studying songbirds have unravelled parts of the mystery surrounding how some genes in an organism are exclusive to certain cells, an advance that may lead to better understanding of diseases like cancer and ageing. The researchers, including ecologist Alexander Sang-Jae Suh from Uppsala University in Sweden, have found that songbirds -- which include nearly half of all bird species on the planet -- may have a whole different chromosome present only in their reproductive cells -- such as sperm and ovum -- and not in their body cells, shedding light on how genes are eliminated from some cells. They said depending on where a gene is present, the trait it contributes can be either helpful or destructive for the organism - a phenomenon called antagonistic pleiotropy.

"Antagonistic pleiotropy means that a trait can have a positive effect in one context but a negative effect in another context," Suh told PTI. By this phenomenon, the researchers explained, when a gene codes for more than one trait, one of them can have a positive effect in a chromosome, but a negative effect in another.

Chromosomes are thread-like structures located inside the nucleus of animal and plant cells. They contain proteins wrapped around a single molecule of deoxyribonucleic acid (DNA), which has instructions that make each living organism unique, and is passed from one generation to the other in the form of genes.

The researchers explained that during the development of an embryo, cells are divided into two main types -- germ cells (found in the reproductive organs), and somatic cells (forming the rest of the body).

Based on earlier studies, they said, certain genes are exclusive to somatic or germ cells, meaning that all cells in an organism do not contain the same genome. The process by which these gene eliminations happen has intrigued scientists for their possible roles in diseases like cancer, the study, published recently in the journal Nature Communications, noted.

The researchers of the current study sampled the genome of the songbird -- zebra finches -- and analysed a special chromosome called the Germline-restricted chromosome (GRC), found exclusively in the bird's germ cells.

According to the researchers, the GRC is the largest chromosome in zebra finches, and accounts for more than 10 per cent of its entire genome. The findings of the study revealed that the GRC -- which came into existence in birds tens of millions of years ago -- plays an important role in songbird biology as it contains genes that are important for the development of the embryo.

The study noted that some of the genes found in the GRC were replicated tens or hundreds of times in the reproductive cells, while the body cells had very few of them.

They said, over the course of evolution of birds over millions of years, the genes present in the GRC were systematically deleted from other chromosomes in the somatic cells, making the GRC exclusive to the germline. They explained this elimination may have been due to the negative impacts created by genes in the GRC when they were present in the non-reproductive, body cells.

"What was proposed previously for programmed DNA elimination  -- and is implied by the presence of multicopy germline development genes on the GRC -- is that gene expression of these genes is positive in the germline -- eg might enhance differentiation of a cell into specialised ones -- but negative in the soma -- e.g. might lead to cancer," said study lead author Suh.

In GRC, Suh said, these genes are present in many copies in the germline, but only a handful of copies are in the non-reproductive body cells, or soma.

In the current study, the researchers identified specific GRC genes, and compared them with genetic data from other species.

By this process, they retraced the evolutionary history of the chromosome and found that it is tens of millions of years old, and probably found in all songbird species -- which make up about half of all bird species.

"The main significance of our findings is that the GRC is likely present in half of all bird species but was previously overlooked despite the fact that birds are among the best-studied vertebrates in genome research," Suh said.

While the GRC itself was discovered nearly two decades ago, the researchers said, recent developments in genome analysis techniques made the discovery possible.

"There were only a total of five studies on this phenomenon when we started our project in early 2017. What changed in the meantime is that it is now feasible to sequence multiple genomes from the same individual -- i.e. here a liver sample to get a somatic genome and a testis sample to get a germline genome -- and that we developed analysis tools to reliably identify tissue-specific differences in DNA/RNA/protein data," explained Suh.

Another important finding from the study, the researchers said, is the variation of GRC even between closely related songbirds.

"Our phylogenetic analyses suggest that this variation is because the GRC keeps ?receiving? new genes from other chromosomes over time, with most of the zebra finch GRC genes being species-specific or subspecies-specific," Suh said.

The researchers believe more insights on the chromosome may lead to better understanding of the biology of disease and ageing in all organisms.

"This relates to the aspect of minimising antagonistic pleiotropy between germline and soma. If gene expression is suppressed or lower in soma because those genes are absent or in lower copy numbers, then this could lower the effect of sporadic 'mistakes' in gene expression, and that could lead to diseases such as cancer or ageing," Suh said.

According to the researchers, even in a well-studied group of organisms such as birds, there can be plenty of surprises when looking more closely.

"It was previously suggested that, compared to other vertebrates, bird genomes are rather slowly evolving and unremarkable - the GRC suggests that at least some birds (Passeriformes aka passerines) are very special in this regard," Suh said.

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First Published : 10 Dec 2019, 08:33:26 AM

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