In genetics, an isochore is a large region of DNA (greater than 300 kb) with a high degree uniformity in guanine (G) and cytosine (C): G-C and C-G (collectively GC content).
Bernardi and colleagues first uncovered the compositional non-uniformity within vertebrate genomes using thermal melting and density gradient centrifugation. [1] [2] [3] The DNA fragments extracted by the gradient centrifugation were later termed "isochores", [4] which was subsequently defined as "very long (much greater than 200 KB) DNA segments" that "are fairly homogeneous in base composition and belong to a small number of major classes distinguished by differences in guanine-cytosine (GC) content". [3] Subsequently, the isochores "grew" and were claimed to be ">300 kb in size." [5] [6] The theory proposed that isochore’s composition varied markedly between "warm-blooded" (homeotherm) vertebrates and "cold-blooded" (poikilotherm) vertebrates [3] and later became known as the isochore theory.
The isochore theory purported that the genome of "warm-blooded" vertebrates (mammals and birds) are mosaics of long isochoric regions of alternating GC-poor and GC-rich composition, as opposed to the genome of "cold-blooded" vertebrates (fishes and amphibians) that were supposed to lack GC-rich isochores. [3] [7] [8] [9] [10] [11] These findings were explained by the thermodynamic stability hypothesis, attributing genomic structure to body temperature. GC-rich isochores were purported to be a form of adaptation to environmental pressures, as an increase in genomic GC-content could protect DNA, RNA, and proteins from degradation by heat. [3] [4] Despite its attractive simplicity, the thermodynamic stability hypothesis has been repeatedly shown to be in error [12] [13] [14] . [15] [16] [17] [18] [19] Many authors showed the absence of a relationship between temperature and GC-content in vertebrates, [17] [18] while others showed the existence of GC-rich domains in "cold-blooded" vertebrates such as crocodiles, amphibians, and fish. [14] [20] [21] [22]
The isochore theory was the first to identify the nonuniformity of nucleotide composition within vertebrate genomes and predict that the genome of "warm-blooded" vertebrates such as mammals and birds are mosaic of isochores (Bernardi et al. 1985). The human genome, for example, was described as a mosaic of alternating low and high GC content isochores belonging to five compositional families, L1, L2, H1, H2, and H3, whose corresponding ranges of GC contents were said to be <38%, 38%-42%, 42%-47%, 47%-52%, and >52%, respectively. [23]
The main predictions of the isochore theory are that:
Two opposite explanations that endeavored to explain the formations of isochores were vigorously debated as part of the neutralist-selectionist controversy. The first view was that isochores reflect variable mutation processes among genomic regions consistent with the neutral model. [26] [27] Alternatively, isochores were posited as a result of natural selection for certain compositional environment required by certain genes. [28] Several hypotheses derive from the selectionist view, such as the thermodynamic stability hypothesis [6] [29] and the biased gene conversion hypothesis. [27] Thus far, none of the theories provides a comprehensive explanation to the genome structure, and the topic is still under debate.
The isochore theory became one of the most useful theories in molecular evolution for many years. It was the first and most comprehensive attempt to explain the long-range compositional heterogeneity of vertebrate genomes within an evolutionary framework. Despite the interest in the early years in the isochore model, in recent years, the theory’s methodology, terminology, and predictions have been challenged.
Because this theory was proposed in the 20th century before complete genomes were sequenced, it could not be fully tested for nearly 30 years. In the beginning of the 21st century, when the first genomes were made available it was clear that isochores do not exist in the human genome [30] nor in other mammalian genomes. [31] When failed to find isochores, many attacked the very existence of isochores. [30] [32] [33] [34] [35] The most important predictor of isochores, GC3 was shown to have no predictable power [36] [37] to the GC content of nearby genomic regions, refuting findings from over 30 years of research, which were the basis for many isochore studies. Isochore-originators replied that the term was misinterpreted [23] [38] [39] as isochores are not "homogeneous" but rather fairly homogeneous regions with a heterogeneous nature (especially) of GC-rich regions at the 5 kb scale, [40] which only added to the already growing confusion. The reason for this ongoing frustration was the ambiguous definition of isochores as long and homogeneous, allowed some researchers to discover "isochores" and others to dismiss them, although both camps used the same data.
The unfortunate side effect of this controversy was an "arms race" in which isochores are frequently redefined and relabeled following conflicting findings that failed to reveal "mosaic of isochores." [23] [32] [34] The unfortunate outcomes of this controversy and the following terminological-methodological mud were the loss of interest in isochores by the scientific community. When the most important core-concept in isochoric literature, the thermodynamic stability hypothesis, was rejected, the theory lost its appeal. Even today, there is no clear definition to isochores nor is there an algorithm that detects isochores. [41] Isochores are detected manually by visual inspection of GC content curves , [42] however because this approach lacks scientific merit and is difficult to replicate by independent groups, the findings remain disputed.
As the study of isochores was de facto abandoned by most scientists, an alternative theory was proposed to describe the compositional organization of genomes in accordance with the most recent genomic studies. The Compositional Domain Model depicts genomes as a medley of short and long homogeneous and nonhomogeneous domains. [35] The theory defines "compositional domains" as genomic regions with distinct GC-contents as determined by a computational segmentation algorithm. [35] The homogeneity of compositional domains is compared to that of the chromosome on which they reside using the F-test, which separated them into compositionally homogeneous domains and compositionally nonhomogeneous domains based on the outcome of test. Compositionally homogeneous domains that are sufficiently long (≥ 300 kb) are termed isochores or isochoric domains. These terms are in accordance with the literature as they provide clear distinction between isochoric- and nonisochoric-domains.
A comprehensive study of the human genome unraveled a genomic organization where two-thirds of the genome is a mixture of many short compositionally homogeneous domains and relatively few long ones. The remaining portion of the genome is composed of nonhomogeneous domains. In terms of coverage, only 1% of the total number of compositionally homogeneous domains could be considered "isochores" which covered less than 20% of the genome. [35]
Since its inception the theory received wide attention and was extensively used to explain findings emerging from over dozen new genome sequencing studies. [31] [43] [44] [45] [46] [47] [48] [49] [50] yet many important questions remain open, such as which evolutionary forces shaped the structure of compositional domain and how do they differ between different species?
In the fields of molecular biology and genetics, a genome is all genetic information of an organism. It consists of nucleotide sequences of DNA. The genome includes both the genes and the noncoding DNA, as well as mitochondrial DNA and chloroplast DNA. The study of the genome is called genomics. The genome for several organisms have been sequenced and genes analyzed, the human genome project which sequenced the entire genome for Homo sapiens was successfully completed in April 2003.
Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.
The neutral theory of molecular evolution holds that most evolutionary changes occur at the molecular level, and most of the variation within and between species, are due to random genetic drift of mutant alleles that are selectively neutral. The theory applies only for evolution at the molecular level, and is compatible with phenotypic evolution being shaped by natural selection as postulated by Charles Darwin. The neutral theory allows for the possibility that most mutations are deleterious, but holds that because these are rapidly removed by natural selection, they do not make significant contributions to variation within and between species at the molecular level. A neutral mutation is one that does not affect an organism's ability to survive and reproduce. The neutral theory assumes that most mutations that are not deleterious are neutral rather than beneficial. Because only a fraction of gametes are sampled in each generation of a species, the neutral theory suggests that a mutant allele can arise within a population and reach fixation by chance, rather than by selective advantage.
The coding region of a gene, also known as the coding DNA sequence(CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to non-coding regions over different species and time periods can provide a significant amount of important information regarding gene organization and evolution of prokaryotes and eukaryotes. This can further assist in mapping the human genome and developing gene therapy.
Comparative genomics is a field of biological research in which the genomic features of different organisms are compared. The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural landmarks. In this branch of genomics, whole or large parts of genomes resulting from genome projects are compared to study basic biological similarities and differences as well as evolutionary relationships between organisms. The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionarily conserved between them. Therefore, comparative genomic approaches start with making some form of alignment of genome sequences and looking for orthologous sequences in the aligned genomes and checking to what extent those sequences are conserved. Based on these, genome and molecular evolution are inferred and this may in turn be put in the context of, for example, phenotypic evolution or population genetics.
The Rickettsiales, informally called rickettsias, are an order of small Alphaproteobacteria. They are obligate intracellular parasites, and some are notable pathogens, including Rickettsia, which causes a variety of diseases in humans, and Ehrlichia, which causes diseases in livestock. Another genus of well-known Rickettsiales is the Wolbachia, which infect about two-thirds of all arthropods and nearly all filarial nematodes. Genetic studies support the endosymbiotic theory according to which mitochondria and related organelles developed from members of this group.
In molecular biology and genetics, GC-content is the percentage of nitrogenous bases in a DNA or RNA molecule that are either guanine (G) or cytosine (C). This measure indicates the proportion of G and C bases out of an implied four total bases, also including adenine and thymine in DNA and adenine and uracil in RNA.
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speciation event (orthologs), or a duplication event (paralogs), or else a horizontal gene transfer event (xenologs).
Gene conversion is the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion event. Gene conversion can be either allelic, meaning that one allele of the same gene replaces another allele, or ectopic, meaning that one paralogous DNA sequence converts another.
Alphaproteobacteria is a class of bacteria in the phylum Proteobacteria. Its members are highly diverse and possess few commonalities, but nevertheless share a common ancestor. Like all Proteobacteria, its members are gram-negative and some of its intracellular parasitic members lack peptidoglycan and are consequently gram variable.
In bioinformatics, k-mers are substrings of length contained within a biological sequence. Primarily used within the context of computational genomics and sequence analysis, in which k-mers are composed of nucleotides, k-mers are capitalized upon to assemble DNA sequences, improve heterologous gene expression, identify species in metagenomic samples, and create attenuated vaccines. Usually, the term k-mer refers to all of a sequence's subsequences of length , such that the sequence AGAT would have four monomers, three 2-mers, two 3-mers and one 4-mer (AGAT). More generally, a sequence of length will have k-mers and total possible k-mers, where is number of possible monomers.
Plant evolution is the subset of evolutionary phenomena that concern plants. Evolutionary phenomena are characteristics of populations that are described by averages, medians, distributions, and other statistical methods. This distinguishes plant evolution from plant development, a branch of developmental biology which concerns the changes that individuals go through in their lives. The study of plant evolution attempts to explain how the present diversity of plants arose over geologic time. It includes the study of genetic change and the consequent variation that often results in speciation, one of the most important types of radiation into taxonomic groups called clades. A description of radiation is called a phylogeny and is often represented by type of diagram called a phylogenetic tree.
Aequornithes, or core water birds are defined as "the least inclusive clade containing Gaviidae and Phalacrocoracidae".
In the fields of molecular biology and genetics, a pan-genome is the entire set of genes from all strains within a clade. More generally, it is the union of all the genomes of a clade. The pan-genome can be broken down into a "core pangenome" that contains genes present in all individuals, a "shell pangenome" that contains genes present in two or more strains, and a "cloud pangenome" that contains genes only found in a single strain. Some authors also refer to the cloud genome as "accessory genome" containing 'dispensable' genes present in a subset of the strains and strain-specific genes. Note that the use of the term 'dispensable' has been questioned, at least in plant genomes, as accessory genes play "an important role in genome evolution and in the complex interplay between the genome and the environment". The field of study of the pangenome is called pangenomics.
Evolution of cells refers to the evolutionary origin and subsequent evolutionary development of cells. Cells first emerged at least 3.8 billion years ago, approximately 750 million years after the earth was formed.
A compositional domain in genetics is a region of DNA with a distinct guanine (G) and cytosine (C) G-C and C-G content. The homogeneity of compositional domains is compared to that of the chromosome on which they reside. As such, compositional domains can be homogeneous or nonhomogeneous domains. Compositionally homogeneous domains that are sufficiently long are termed isochores or isochoric domains.
Long interspersed nuclear elements (LINEs) are a group of non-LTR retrotransposons that are widespread in the genome of many eukaryotes. They make up around 21.1% of the human genome. LINEs make up a family of transposons, where each LINE is about 7,000 base pairs long. LINEs are transcribed into mRNA and translated into protein that acts as a reverse transcriptase. The reverse transcriptase makes a DNA copy of the LINE RNA that can be integrated into the genome at a new site.
Horizontal or lateral gene transfer is the transmission of portions of genomic DNA between organisms through a process decoupled from vertical inheritance. In the presence of HGT events, different fragments of the genome are the result of different evolutionary histories. This can therefore complicate the investigations of evolutionary relatedness of lineages and species. Also, as HGT can bring into genomes radically different genotypes from distant lineages, or even new genes bearing new functions, it is a major source of phenotypic innovation and a mechanism of niche adaptation. For example, of particular relevance to human health is the lateral transfer of antibiotic resistance and pathogenicity determinants, leading to the emergence of pathogenic lineages.
De novo gene birth is the process by which new genes evolve from DNA sequences that were ancestrally non-genic. De novo genes represent a subset of novel genes, and may be protein-coding or instead act as RNA genes. The processes that govern de novo gene birth are not well understood, although several models exist that describe possible mechanisms by which de novo gene birth may occur.