4 C

4.1 Talking Glossary: Candidate gene

National Human Genome Research Institute https://www.genome.gov/genetics-glossary/Candidate-Gene

Introduction: National Human Genome Research InstituteA candidate gene is a gene whose chromosomal location is associated with a particular disease or other phenotype. Because of its location, the gene is suspected of causing the disease or other phenotype.

Audio: https://www.genome.gov/sites/default/files/tg/en/narration/cancer.mp3

Transcript: A candidate gene is a gene whose chromosomal location fits with a particular disease or phenotype that you’re looking for. An example of this is when you’re doing any type of linkage analysis and you’re trying to find the disease gene that’s associated with that particular disease. You use what we call genetic markers, and the markers will tell you, okay, based on what you see, the recombination frequency, etc., the gene has to be between marker X and marker Y. And what that means is that this distance between marker X and marker Y constitutes your candidate region, and all the genes in that region will be a candidate gene. And now the next thing for you to do is then to look individually at each of those genes to see if they have the mutation that’s associated with the disease that you’re looking for.

Milton English, Ph.D.

4.2 CATH database

Modified from Wikipedia https://en.wikipedia.org/wiki/CATH_database

The CATH Protein Structure Classification database is a free, publicly available online resource that provides information on the evolutionary relationships of protein domains. It was created in the mid-1990s by Professor Christine Orengo and colleagues including Janet Thornton and David Jones (2), and continues to be developed by the Orengo group at University College London. CATH shares many broad features with the SCOP resource, however there are also many areas in which the detailed classification differs greatly (3, 4, 5, 6).

4.2.1 References

  1. Dawson, NL; Lewis, TE; Das, S; Lees, JG; Lee, D; Ashford, P; Orengo, CA; Sillitoe, I (28 November 2016). “CATH: an expanded resource to predict protein function through structure and sequence”. Nucleic Acids Research. 45 (D1): D289–D295. doi:10.1093/nar/gkw1098. PMC 5210570. PMID 27899584.
  2. Orengo, CA; Michie, AD; Jones, S; Jones, DT; Swindells, MB; Thornton, JM (1997). “CATH – a hierarchic classification of protein domain structures”. Structure. 5 (8): 1093–1109. doi:10.1016/S0969-2126(97)00260-8. ISSN 0969-2126. PMID 9309224.
  3. “CATH: Protein Structure Classification Database at UCL”. Cathdb.info. Retrieved 9 March 2017.
  4. “CATH”. Cathdb.info. Retrieved 9 March 2017.
  5. “CATH Database (@CATHDatabase)”. Twitter. Retrieved 9 March 2017.
  6. Pearl, F. M. G. (2003). “The CATH database: an extended protein family resource for structural and functional genomics”. Nucleic Acids Research. 31 (1): 452–455. doi:10.1093/nar/gkg062. ISSN 1362-4962. PMC 165509. PMID 12520050.
  7. “Tools”. cathdb.info. Retrieved 18 December 2016.

4.3 Clade

Adapted from Wikipedia https://en.wikipedia.org/wiki/Clade

A clade, also known as a monophyletic group, is a group of organisms that are monophyletic —that is, composed of a common ancestor and all its descendants .[4] . The common ancestor may be an individual, a population , a species (extinct or extant ), and so on. Clades are nested, one in another, as each branch in turn splits into smaller branches. These splits reflect evolutionary history as populations diverged and evolved independently. The term “clade” is also used with a similar meaning in other fields besides biology, such as historical linguistics.

A clade is by definition monophyletic , meaning that it contains one ancestor (which can be an organism, a population, or a species) and all its descendants.[note 1] [12] [13] The ancestor can be known or unknown; any and all members of a clade can be extant or extinct.

Figure 4.1: Figure 1: Cladogram (family tree) of a biological group. The last common ancestor is the vertical line stem at the bottom. The blue and red subgroups are clades; each shows its common ancestor stem at the bottom of the subgroup branch. The green subgroup is not a clade; it is a non-monophyletic group , because it excludes the blue branch, even though it has also descended from a common ancestor. The green subgroup together with the blue one forms a clade again.

Over the last few decades, the cladistic approach has revolutionized biological classification and revealed surprising evolutionary relationships among organisms.[5] Taxonomists have worked to make the taxonomic system reflect evolution. Taxonomists therefore try to avoid naming taxa that are not clades; that is, taxa that are not monophyletic . Some of the relationships between organisms that the molecular biology arm of cladistics has revealed are that fungi are closer relatives to animals than they are to plants, archaea are now considered different from bacteria , and multicellular organisms may have evolved from archaea.[6]

Figure 4.2: Gavialidae, Crocodylidae and Alligatoridae are clade names that are here applied to a phylogenetic tree of crocodylians.

Many commonly named groups, rodents and insects for example, are clades because, in each case, the group consists of a common ancestor with all its descendant branches. Rodents, for example, are a branch of mammals that split off after the end of the period when the clade Dinosauria stopped being the dominant terrestrial vertebrates 66 million years ago. The original population and all its descendants are a clade. The rodent clade corresponds to the order Rodentia, and insects to the class Insecta. These clades include smaller clades, such as chipmunk or ant , each of which consists of even smaller clades. The clade “rodent” is in turn included in the mammal, vertebrate and animal clades.

4.3.1 Clades and phylogenetic trees

The science that tries to reconstruct phylogenetic trees and thus discover clades is called phylogenetics . The results of phylogenetic analyses are tree-shaped diagrams called phylogenies; they, and all their branches, are phylogenetic hypotheses.[14]

4.3.2 Terminology

The relationship between clades can be described in several ways:

  1. A clade located within a clade is said to be nested within that clade. In the diagram, the hominoid clade, i.e. the apes and humans, is nested within the primate clade.
  2. Two clades are sisters (sister groups sister clades) if they have an immediate common ancestor. In the diagram, lemurs and lorises are sister clades, while humans and tarsiers are not.

Figure 4.3: Cladogram of modern primate groups; all tarsiers are haplorhines, but not all haplorhines are tarsiers; all apes are catarrhines, but not all catarrhines are apes; etc.

4.3.4 References

  1. Wells, John C. (2008). Longman Pronunciation Dictionary (3rd ed.). Longman. ISBN 978-1-4058-8118-0. “clade”. Merriam-Webster Dictionary. Retrieved 19 April 2020. Martin, Elizabeth; Hin, Robert (2008). A Dictionary of Biology. Oxford University Press.
  2. Cracraft, Joel; Donoghue, Michael J., eds. (2004). “Introduction”. Assembling the Tree of Life. Oxford University Press. p. 1. ISBN 978-0-19-972960-9.
  3. Palmer, Douglas (2009). Evolution: The Story of Life. Berkeley: University of California Press. p. 13.
  4. Pace, Norman R. (18 May 2006). “Time for a change”. Nature. 441 (7091): 289. Bibcode:2006Natur.441..289P. doi:10.1038/441289a. ISSN 1476-4687. PMID 16710401. S2CID 4431143.
  5. Dupuis, Claude (1984). “Willi Hennig’s impact on taxonomic thought”. Annual Review of Ecology and Systematics. 15: 1–24. doi:10.1146/annurev.es.15.110184.000245.
  6. Huxley, J. S. (1957). “The three types of evolutionary process”. Nature. 180 (4584): 454–455. Bibcode:1957Natur.180..454H. doi:10.1038/180454a0. S2CID 4174182.
  7. Huxley, T.H. (1876): Lectures on Evolution. New York Tribune. Extra. no 36. In Collected Essays IV: pp 46-138 original text w/ figures
  8. Brower, Andrew V. Z. (2013). “Willi Hennig at 100”. Cladistics. 30 (2): 224–225. doi:10.1111/cla.12057.
  9. ”Evolution 101”. page 10. Understanding Evolution website. University of California, Berkeley. Retrieved 26 February 2016.
  10. “International Code of Phylogenetic Nomenclature. Version 4c. Chapter I. Taxa”. 2010. Retrieved 22 September 2012.
  11. Envall, Mats (2008). “On the difference between mono-, holo-, and paraphyletic groups: a consistent distinction of process and pattern”. Biological Journal of the Linnean Society. 94: 217. doi:10.1111/j.1095-8312.2008.00984.x.
  12. Nixon, Kevin C.; Carpenter, James M. (1 September 2000). “On the Other”Phylogenetic Systematics”“. Cladistics. 16 (3): 298–318. doi:10.1111/j.1096-0031.2000.tb00285.x. S2CID 73530548.

4.4 Talking Glossary: Cloning (0.5 min)

National Human Genome Research Institute https://www.genome.gov/genetics-glossary/Cloning

Introduction: “Cloning is the process of making identical copies of an organism, cell, or DNA sequence. Molecular cloning is a process by which scientists amplify a desired DNA sequence. The target sequence is isolated, inserted into another DNA molecule (known as a vector), and introduced into a suitable host cell. Then, each time the host cell divides, it replicates the foreign DNA sequence along with its own DNA. Cloning also can refer to asexual reproduction.”

Audio: https://www.genome.gov/sites/default/files/tg/en/narration/cloning.mp3

Transcript: “Cloning is a word we use to describe a molecular process of making millions or billions of copies of a single molecule. It’s different from the uses of the terms”cellular cloning” or “organism cloning” that are used in the reproductive genetics universe. We use molecular cloning to amplify, or make many copies of, genes or proteins or other micro molecules that amplifies the signal and allows us to study these molecules in a laboratory”.

Leslie G. Biesecker, M.D.

4.5 Talking Glossary: Codominance (0.5 min)

Abstract: “Codominance is a relationship between two versions of a gene. Individuals receive one version of a gene, called an allele, from each parent. If the alleles are different, the dominant allele usually will be expressed, while the effect of the other allele, called recessive, is masked. In codominance, however, neither allele is recessive and the phenotypes of both alleles are expressed.”

Audio: https://www.genome.gov/sites/default/files/tg/en/narration/codominance.mp3

Image: https://www.genome.gov/sites/default/files/tg/en/illustration/codominance.jpg Transcript

Codominance means that neither allele can mask the expression of the other allele. An example in humans would be the ABO blood group, where alleles A and alleles B are both expressed. So if an individual inherits allele A from their mother and allele B from their father, they have blood type AB.

Suzanne Hart, Ph.D.

4.6 Comparative genomics

Adapted from Wikipedia

https://en.wikipedia.org/wiki/Comparative_genomics

Comparative genomics is a field of biological research in which the genomic features of different organisms are compared.[2][3] The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural landmarks.[3] In this branch of genomics, whole genomes resulting from genome projects are compared to study basic biological similarities and differences as well as evolutionary relationships between organisms.[2][4][5] 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.[6] Therefore, comparative genomic approaches start with making some form of alignment of genome sequences and looking for similar 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, evolution, ecology, or pathogenicity.

Comparative genomics is now a standard component of the analysis of every new genome sequence.[2][8] With the explosion in the number of genome projects due to the advancements in DNA sequencing technologies[9] Comparative genomics has revealed high levels of similarity between closely related organisms, such as humans and chimpanzees, and, more surprisingly, similarity between seemingly distantly related organisms, such as humans and yeast.

The medical field benefits from the study of comparative genomics. Vaccine development in particular has experienced useful advances in technology due to genomic approaches to problems. In an approach known as reverse vaccinology, researchers can discover candidate antigens (proteins in pathogens that can be targeted by the immune system) for vaccine development by analyzing the genome of a pathogen or a family of pathogens.

1* Darling A.E.; Miklós I.; Ragan M.A. (2008). “Dynamics of Genome Rearrangement in Bacterial Populations”. PLOS Genetics. 4 (7): e1000128. doi:10.1371/journal.pgen.1000128. PMC 2483231. PMID 18650965. open access 1. Touchman, J. (2010). “Comparative Genomics”. Nature Education Knowledge. 3 (10): 13. 1. Xia, X. (2013). Comparative Genomics. SpringerBriefs in Genetics. Heidelberg: Springer. doi:10.1007/978-3-642-37146-2. ISBN 978-3-642-37145-5. S2CID 5491782. 1. Russel, P.J.; Hertz, P.E.; McMillan, B. (2011). Biology: The Dynamic Science (2nd ed.). Belmont, CA: Brooks/Cole. pp. 409–410. 1. Primrose, S.B.; Twyman, R.M. (2003). Principles of Genome Analysis and Genomics (3rd ed.). Malden, MA: Blackwell Publishing. 1. Hardison, R.C. (2003). “Comparative genomics”. PLOS Biology. 1 (2): e58. doi:10.1371/journal.pbio.0000058. PMC 261895. PMID 14624258. open access 1. Ellegren, H. (2008). “Comparative genomics and the study of evolution by natural selection”. Molecular Ecology. 17 (21): 4586–4596. doi:10.1111/j.1365-294X.2008.03954.x. PMID 19140982. S2CID 43171654. 1. Koonin, E.V.; Galperin, M.Y. (2003). Sequence - Evolution - Function: Computational approaches in comparative genomics. Dordrecht: Springer Science+Business Media.

4.7 Talking Glossary: Contig (0.75 min)

https://www.genome.gov/genetics-glossary/Contig

Abstract: “A contig–from the word”contiguous”–is a series of overlapping DNA sequences used to make a physical map that reconstructs the original DNA sequence of a chromosome or a region of a chromosome. A contig can also refer to one of the DNA sequences used in making such a map.”

Audio: https://www.genome.gov/sites/default/files/tg/en/narration/contig.mp3

Image: https://www.genome.gov/sites/default/files/tg/en/narration/contig.mp3

Transcript: “A chromosome is a very long molecule of DNA. And it is very hard to study it at once, so what researchers do is they break it into smaller pieces and they sequence each one of those individual pieces first, and then they attempt to put it together to reconstruct the original chromosome sequence. A contig is the physical map, which results from putting together several little overlapping bits of DNA into a longer sequence. The contig is the physical map resulting from taking small pieces of DNA that overlap and putting them together into a longer sequence.”

Belen Hurle, Ph.D.

4.8 Talking Glossary - Foundations 1 Review: Crossing over

Abstract: “Crossing over is the swapping of genetic material that occurs in the germ line. During the formation of egg and sperm cells, also known as meiosis, paired chromosomes from each parent align so that similar DNA sequences from the paired chromosomes cross over one another. Crossing over results in a shuffling of genetic material and is an important cause of the genetic variation seen among offspring.”

Audio: https://www.genome.gov/sites/default/files/tg/en/narration/crossing_over.mp3

Transcript: “Crossing over is a biological occurrence that happens during meiosis when the paired homologs, or chromosomes of the same type, are lined up. In meiosis, they’re lined up on the meiotic plates, [as they’re] sometimes called, and those paired chromosomes then have to have some biological mechanism that sort of keeps them together. And it turns out that there are these things called chiasmata, which are actually where strands of the duplicated homologous chromosomes break and recombine with the same strand of the other homolog. So if you have two Chromosome 1s lined up, one strand of one Chromosome 1 will break and it will reanneal with a similar breakage on the other Chromosome 1. So that then the new chromosome that will happen will have part of, say, the maternal Chromosome 1 and the paternal Chromosome 1, where maternal and paternal means where that person got their Chromosomes 1s from, their one or their two. Therefore, the child that’s formed out of one of those Chromosome 1s now has a piece of his or her grandmother’s Chromosome 1 and a piece of his or her grandfather’s Chromosome 1. And it’s this crossing over that lets recombination across generations of genetic material happen, and it also allows us to use that information to find the locations of genes.”

Joan E. Bailey-Wilson, Ph.D

Photo: https://i.irp.nih.gov/pi/0010100622.jpg