Tuesday, March 11, 2025

Why Is It So Hard To Rewrite a Genome?

Malte Mueller/Getty

When Patrick Yizhi Cai reflects on the state of synthetic genomics, he recalls the Big DNA Contest. Launched in 2004, the competition challenged synthetic biologists to design a novel, functional 40,000-base-pair DNA sequence that the contest sponsor, US DNA-synthesis firm Blue Heron Biotech (now Eurofins Genomics Blue Heron) would manufacture for free…….Continue reading….

By: Michael Eisenstein

Source: Nature

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Critics:

A genome is all the genetic information of an organism.[1] It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences (see non-coding DNA), and often a substantial fraction of junk DNA with no evident function. Almost alleukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome.

The study of the genome is called genomics. The genomes of many organisms have been sequenced and various regions have been annotated. The first genome to be sequenced was that of the virus φX174 in 1977; the first genome sequence of a prokaryote (Haemophilus influenzae) was published in 1995; the yeast (Saccharomyces cerevisiae) genome was the first eukaryotic genome to be sequenced in 1996.

The Human Genome Project was started in October 1990, and the first draft sequences of the human genome were reported in February 2001. The term genome was created in 1920 by Hans Winkler, professor of botany at the University of Hamburg, Germany. The website Oxford Dictionaries and the Online Etymology Dictionary suggest the name is a blend of the words gene and chromosome. However, see omics for a more thorough discussion. A few related -ome words already existed, such as biome and rhizome, forming a vocabulary into which genome fits systematically.

The term “genome” usually refers to the DNA (or sometimes RNA) molecules that carry the genetic information in an organism, but sometimes it is uncertain which molecules to include; for example, bacteria usually have one or two large DNA molecules (chromosomes) that contain all of the essential genetic material but they also contain smaller extrachromosomal plasmid molecules that carry important genetic information. In the scientific literature, the term ‘genome’ usually refers to the large chromosomal DNA molecules in bacteria.

Eukaryotic genomes are even more difficult to define because almost all eukaryotic species contain nuclear chromosomes plus extra DNA molecules in the mitochondria. In addition, algae and plants have chloroplast DNA. Most textbooks make a distinction between the nuclear genome and the organelle (mitochondria and chloroplast) genomes so when they speak of, say, the human genome, they are only referring to the genetic material in the nucleus. This is the most common use of ‘genome’ in the scientific literature.

Most eukaryotes are diploid, meaning that there are two of each chromosome in the nucleus but the ‘genome’ refers to only one copy of each chromosome. Some eukaryotes have distinctive sex chromosomes, such as the X and Y chromosomes of mammals, so the technical definition of the genome must include both copies of the sex chromosomes. For example, the standard reference genome of humans consists of one copy of each of the 22 autosomes plus one X chromosome and one Y chromosome.[

Genome size is the total number of the DNA base pairs in one copy of a haploid genome. Genome size varies widely across species. Invertebrates have small genomes, this is also correlated to a small number of transposable elements. Fish and Amphibians have intermediate-size genomes, and birds have relatively small genomes but it has been suggested that birds lost a substantial portion of their genomes during the phase of transition to flight.  Before this loss, DNA methylation allows the adequate expansion of the genome.

In humans, the nuclear genome comprises approximately 3.1 billion nucleotides of DNA, divided into 24 linear molecules, the shortest 45 000 000 nucleotides in length and the longest 248 000 000 nucleotides, each contained in a different chromosome. There is no clear and consistent correlation between morphological complexity and genome size in either prokaryotes or lower eukaryotes. Genome size is largely a function of the expansion and contraction of repetitive DNA elements.

Since genomes are very complex, one research strategy is to reduce the number of genes in a genome to the bare minimum and still have the organism in question survive. There is experimental work being done on minimal genomes for single cell organisms as well as minimal genomes for multi-cellular organisms (see developmental biology). The work is both in vivo and in silico.

There are many enormous differences in size in genomes, specially mentioned before in the multicellular eukaryotic genomes. Much of this is due to the differing abundances of transposable elements, which evolve by creating new copies of themselves in the chromosomes. Eukaryote genomes often contain many thousands of copies of these elements, most of which have acquired mutations that make them defective.

All the cells of an organism originate from a single cell, so they are expected to have identical genomes; however, in some cases, differences arise. Both the process of copying DNA during cell division and exposure to environmental mutagens can result in mutations in somatic cells. In some cases, such mutations lead to cancer because they cause cells to divide more quickly and invade surrounding tissues. In certain lymphocytes in the human immune system, 

V(D)J recombination generates different genomic sequences such that each cell produces a unique antibody or T cell receptors. During meiosis, diploid cells divide twice to produce haploid germ cells. During this process, recombination results in a reshuffling of the genetic material from homologous chromosomes so each gamete has a unique genome.

Molecular and Genome Evolution.

The Fragmented Gene”

Verbreitung und Ursache der Parthenogenesis im Pflanzen- und Tierreichedefinition of Genome in Oxford dictionary”.

genome”Oxford English Dictionary 

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All about genes”

Genome Home”.

 Toe Fossil Provides Complete Neanderthal Genome”.

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Archaeal chromosome biology”

Replication of Linear Bacterial Chromosomes: No Longer Going Around in Circles”

Bacterial Chromosomes”.

Constraints and plasticity in genome and molecular-phenome evolution”.

 Insights from 20 years of bacterial genome sequencing”

Scientists sequence asexual tiny worm whose lineage stretches back 18 million years”.

DNA methylation enables transposable element-driven genome expansion”

The biological effects of simple tandem repeats: lessons from the repeat expansion diseases”

Microsatellites: genomic distribution, putative functions and mutational mechanisms: a review”

Transposable elements and the evolution of eukaryotic genomes”

Transposon | genetics”.

Comparative genomics and molecular dynamics of DNA repeats in eukaryotes”

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Labels: genome,molecular,putative,DNA,evolution,eukaryotic ,Bacterial, Chromosome,gene ,annotation,synthetic,biology

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