4PWN
75-403: 65125 232341 ENSG00000060237 ENSMUSG00000045962 Q9H4A3 P83741 NM_001184985 NM_014823 NM_018979 NM_213655 NM_198703 NP_001171914 NP_055638 NP_061852 NP_998820 NP_001171949 NP_001171950 NP_001186012 NP_001186013 NP_941992 WNK (lysine deficient protein kinase 1) , also known as WNK1 , is an enzyme that is encoded by
150-588: A promoter sequence. The promoter is recognized and bound by transcription factors that recruit and help RNA polymerase bind to the region to initiate transcription. The recognition typically occurs as a consensus sequence like the TATA box . A gene can have more than one promoter, resulting in messenger RNAs ( mRNA ) that differ in how far they extend in the 5' end. Highly transcribed genes have "strong" promoter sequences that form strong associations with transcription factors, thereby initiating transcription at
225-527: A " start codon ", and three " stop codons " indicate the beginning and end of the protein coding region . There are 64 possible codons (four possible nucleotides at each of three positions, hence 4 possible codons) and only 20 standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organisms. Distal convoluted tubule The distal convoluted tubule ( DCT )
300-402: A HQ domain that is needed for WNK1 interactions with other WNKs. The interactions between WNKs play an important role in function; WNK1 mutants that lack an HQ domain also lack kinase activity. The WNK1 gene encodes a cytoplasmic serine-threonine kinase expressed in the distal nephron . Studies have shown that WNK1 can activate multiple CCCs. WNK1 however, does not directly phosphorylate
375-445: A continuous messenger RNA , referred to as a polycistronic mRNA . The term cistron in this context is equivalent to gene. The transcription of an operon's mRNA is often controlled by a repressor that can occur in an active or inactive state depending on the presence of specific metabolites. When active, the repressor binds to a DNA sequence at the beginning of the operon, called the operator region , and represses transcription of
450-498: A double-helix run in opposite directions. Nucleic acid synthesis, including DNA replication and transcription occurs in the 5'→3' direction, because new nucleotides are added via a dehydration reaction that uses the exposed 3' hydroxyl as a nucleophile . The expression of genes encoded in DNA begins by transcribing the gene into RNA , a second type of nucleic acid that is very similar to DNA, but whose monomers contain
525-488: A few genes and are transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, via horizontal gene transfer . Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas
600-434: A gene - surprisingly, there is no definition that is entirely satisfactory. A gene is a DNA sequence that codes for a diffusible product. This product may be protein (as is the case in the majority of genes) or may be RNA (as is the case of genes that code for tRNA and rRNA). The crucial feature is that the product diffuses away from its site of synthesis to act elsewhere. The important parts of such definitions are: (1) that
675-573: A gene corresponds to a transcription unit; (2) that genes produce both mRNA and noncoding RNAs; and (3) regulatory sequences control gene expression but are not part of the gene itself. However, there's one other important part of the definition and it is emphasized in Kostas Kampourakis' book Making Sense of Genes . Therefore in this book I will consider genes as DNA sequences encoding information for functional products, be it proteins or RNA molecules. With 'encoding information', I mean that
750-410: A gene may be split across chromosomes but those transcripts are concatenated back together into a functional sequence by trans-splicing . It is also possible for overlapping genes to share some of their DNA sequence, either on opposite strands or the same strand (in a different reading frame, or even the same reading frame). In all organisms, two steps are required to read the information encoded in
825-404: A gene's DNA and produce the protein it specifies. First, the gene's DNA is transcribed to messenger RNA ( mRNA ). Second, that mRNA is translated to protein. RNA-coding genes must still go through the first step, but are not translated into protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression , and the resulting molecule
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#1732801191686900-578: A gene: that of bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool. An automated version of the Sanger method was used in early phases of the Human Genome Project . The theories developed in the early 20th century to integrate Mendelian genetics with Darwinian evolution are called
975-439: A gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence. The majority of eukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within the nucleus in complex with storage proteins called histones to form a unit called a nucleosome . DNA packaged and condensed in this way is called chromatin . The manner in which DNA
1050-448: A high rate. Others genes have "weak" promoters that form weak associations with transcription factors and initiate transcription less frequently. Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters. Additionally, genes can have regulatory regions many kilobases upstream or downstream of the gene that alter expression. These act by binding to transcription factors which then cause
1125-499: A loss of peripheral sensory nerves ). The gene belongs to a group of four related protein kinases (WNK1, WNK2 , WNK3 , WNK4 ). Homologs of this protein have been found in Arabidopsis thaliana , C. elegans , Chlamydomonas reinhardtii and Vitis vinifera as well as in vertebrates including Danio rerio and Taeniopygia guttata . Gene In biology , the word gene has two meanings. The Mendelian gene
1200-518: A major role in regulating WNK1 activity. In the DCT, the plasma concentration of K ion is thought to impact the concentration Cl ions within the nephron. High plasma K concentration down regulates WNK1 activity and prevents Cl ion from entering the nephron via the NCC. The opposite occurs when plasma K concentration is low; increased WNK1 activity boosts NCC activity promoting reabsorption of Cl ions. When there
1275-572: A new expanded definition that includes noncoding genes. However, some modern writers still do not acknowledge noncoding genes although this so-called "new" definition has been recognised for more than half a century. Although some definitions can be more broadly applicable than others, the fundamental complexity of biology means that no definition of a gene can capture all aspects perfectly. Not all genomes are DNA (e.g. RNA viruses ), bacterial operons are multiple protein-coding regions transcribed into single large mRNAs, alternative splicing enables
1350-400: A process known as RNA splicing . Finally, the ends of gene transcripts are defined by cleavage and polyadenylation (CPA) sites , where newly produced pre-mRNA gets cleaved and a string of ~200 adenosine monophosphates is added at the 3' end. The poly(A) tail protects mature mRNA from degradation and has other functions, affecting translation, localization, and transport of the transcript from
1425-419: A protein-coding gene consists of many elements of which the actual protein coding sequence is often only a small part. These include introns and untranslated regions of the mature mRNA. Noncoding genes can also contain introns that are removed during processing to produce the mature functional RNA. All genes are associated with regulatory sequences that are required for their expression. First, genes require
1500-412: A single genomic region to encode multiple district products and trans-splicing concatenates mRNAs from shorter coding sequence across the genome. Since molecular definitions exclude elements such as introns, promotors, and other regulatory regions , these are instead thought of as "associated" with the gene and affect its function. An even broader operational definition is sometimes used to encompass
1575-475: A strict definition of the word "gene" with which nearly every expert can agree. First, in order for a nucleotide sequence to be considered a true gene, an open reading frame (ORF) must be present. The ORF can be thought of as the "gene itself"; it begins with a starting mark common for every gene and ends with one of three possible finish line signals. One of the key enzymes in this process, the RNA polymerase, zips along
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#17328011916861650-409: A true gene, by this definition, one has to prove that the transcript has a biological function. Early speculations on the size of a typical gene were based on high-resolution genetic mapping and on the size of proteins and RNA molecules. A length of 1500 base pairs seemed reasonable at the time (1965). This was based on the idea that the gene was the DNA that was directly responsible for production of
1725-451: Is a basic unit of heredity . The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA . There are two types of molecular genes: protein-coding genes and non-coding genes. During gene expression (the synthesis of RNA or protein from a gene), DNA is first copied into RNA . RNA can be directly functional or be the intermediate template for
1800-457: Is a portion of kidney nephron between the loop of Henle and the collecting tubule . It is partly responsible for the regulation of potassium , sodium , calcium , and pH . On its apical surface (lumen side), cells of the DCT have a thiazide-sensitive Na-Cl cotransporter and are permeable to Ca, via the TRPV5 channel. On the basolateral surface (peritubular capillary side) there
1875-517: Is an ATP-dependent Na/K antiporter pump, a secondary active Na/Ca transporter, and an ATP dependent Ca transporter. The basolateral ATP dependent Na/K pump produces the gradient for Na to be absorbed from the apical surface via the Na/Cl symporter , and for Ca to be reclaimed into the blood by the Na/Ca basolateral antiporter. Thiazide diuretics inhibit Na /Cl reabsorption from the DCT by blocking
1950-534: Is an abundance of Cl ions within the nephron , WNK1 activity is inhibited by the binding of a Cl ion to WNK1's catalytic domain. Furthermore, WNK1 and WNK4 may interact to form heterodimers that inhibit WNK1 function. WNK4 release from the heterodimer allows WNK1 monomer to bind another WNK1 monomer to promote activation. WNK1 function can also be inhibited if WNK1 is degraded. There are two enzymes responsible for WNK1 ubiquitination, kelch like 3 (KLHL3) and cullin 3 (CUL3). KLHL3 serves as an adaptor protein that promotes
2025-456: Is called a gene product . The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through the genetic code . Sets of three nucleotides, known as codons , each correspond to a specific amino acid. The principle that three sequential bases of DNA code for each amino acid was demonstrated in 1961 using frameshift mutations in the rIIB gene of bacteriophage T4 (see Crick, Brenner et al. experiment ). Additionally,
2100-400: Is nearly the same for all known organisms. The total complement of genes in an organism or cell is known as its genome , which may be stored on one or more chromosomes . A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded. The region of the chromosome at which a particular gene is located is called its locus . Each locus contains one allele of
2175-403: Is still part of the definition of a gene in most textbooks. For example, The primary function of the genome is to produce RNA molecules. Selected portions of the DNA nucleotide sequence are copied into a corresponding RNA nucleotide sequence, which either encodes a protein (if it is an mRNA) or forms a 'structural' RNA, such as a transfer RNA (tRNA) or ribosomal RNA (rRNA) molecule. Each region of
2250-399: Is stored on the histones, as well as chemical modifications of the histone itself, regulate whether a particular region of DNA is accessible for gene expression . In addition to genes, eukaryotic chromosomes contain sequences involved in ensuring that the DNA is copied without degradation of end regions and sorted into daughter cells during cell division: replication origins , telomeres , and
2325-590: The MEKK protein kinase family. As a member of the WNK family, the kinase's catalytic lysine residue is uniquely located in beta strand 2 of the glycine loop . In order to have kinase activity, WNK1 must autophosphorylate the serine 382 residue found in its activation loop. Further, phosphorylation at another site (Ser378) increases WNK1 activity. An autoinhibitory domain is located within the C-terminal domain along with
WNK1 - Misplaced Pages Continue
2400-507: The WNK1 gene . WNK1 is serine-threonine protein kinase and part of the "with no lysine/K" kinase WNK family. The predominant role of WNK1 is the regulation of cation-Cl cotransporters (CCCs) such as the sodium chloride cotransporter ( NCC ), basolateral Na-K-Cl symporter ( NKCC1 ), and potassium chloride cotransporter (KCC1) located within the kidney. CCCs mediate ion homeostasis and modulate blood pressure by transporting ions in and out of
2475-511: The aging process. The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division . Prokaryotes ( bacteria and archaea ) typically store their genomes on a single, large, circular chromosome . Similarly, some eukaryotic organelles contain a remnant circular chromosome with a small number of genes. Prokaryotes sometimes supplement their chromosome with additional small circles of DNA called plasmids , which usually encode only
2550-403: The cell . WNK1 mutations as a result have been implicated in blood pressure disorders/diseases; a prime example being familial hyperkalemic hypertension (FHHt). The WNK1 protein is composed of 2382 amino acids (molecular weight 230 kDa). The protein contains a kinase domain located within its short N-terminal domain and a long C-terminal tail. The kinase domain has some similarity to
2625-401: The central dogma of molecular biology , which states that proteins are translated from RNA , which is transcribed from DNA . This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses . The modern study of genetics at the level of DNA is known as molecular genetics . In 1972, Walter Fiers and his team were the first to determine the sequence of
2700-419: The centromere . Replication origins are the sequence regions where DNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequences that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions during DNA replication . The length of the telomeres decreases each time the genome is replicated and has been implicated in
2775-557: The distal convoluted tubule (DCT), WNK1 is a potent activator of the NCC that results in an increase in sodium re absorption that drives an increase in blood pressure. The WNK1 mutant found in FHHt harbors a large deletion within intron 1 that causes an increase in the expression of full length WNK1. The boost in WNK1 leads to increases in NCC activation that promotes the high blood pressure/ hypertension associated with FHHt. WNK1 activates
2850-554: The modern synthesis , a term introduced by Julian Huxley . This view of evolution was emphasized by George C. Williams ' gene-centric view of evolution . He proposed that the Mendelian gene is a unit of natural selection with the definition: "that which segregates and recombines with appreciable frequency." Related ideas emphasizing the centrality of Mendelian genes and the importance of natural selection in evolution were popularized by Richard Dawkins . The development of
2925-475: The neutral theory of evolution in the late 1960s led to the recognition that random genetic drift is a major player in evolution and that neutral theory should be the null hypothesis of molecular evolution. This led to the construction of phylogenetic trees and the development of the molecular clock , which is the basis of all dating techniques using DNA sequences. These techniques are not confined to molecular gene sequences but can be used on all DNA segments in
3000-750: The operon ; when the repressor is inactive transcription of the operon can occur (see e.g. Lac operon ). The products of operon genes typically have related functions and are involved in the same regulatory network . Though many genes have simple structures, as with much of biology, others can be quite complex or represent unusual edge-cases. Eukaryotic genes often have introns that are much larger than their exons, and those introns can even have other genes nested inside them . Associated enhancers may be many kilobase away, or even on entirely different chromosomes operating via physical contact between two chromosomes. A single gene can encode multiple different functional products by alternative splicing , and conversely
3075-508: The phenotype of the individual. Most biological traits occur under the combined influence of polygenes (a set of different genes) and gene–environment interactions . Some genetic traits are instantly visible, such as eye color or the number of limbs, others are not, such as blood type , the risk for specific diseases, or the thousands of basic biochemical processes that constitute life . A gene can acquire mutations in its sequence , leading to different variants, known as alleles , in
WNK1 - Misplaced Pages Continue
3150-449: The population . These alleles encode slightly different versions of a gene, which may cause different phenotypical traits. Genes evolve due to natural selection or survival of the fittest and genetic drift of the alleles. There are many different ways to use the term "gene" based on different aspects of their inheritance, selection, biological function, or molecular structure but most of these definitions fall into two categories,
3225-428: The thiazide-sensitive Na-Cl cotransporter . By inhibiting the transporter, thiazide diuretics increase the gradient potential for Na. This increases the activity of the basolateral Na/Ca antiport and causes the increase in calcium reclamation associated with thiazide diuretics. The DCT is lined with simple cuboidal cells that are shorter than those of the proximal convoluted tubule (PCT). The lumen appears larger in
3300-512: The CCCs themselves rather it phosphorylates other serine-threonine kinases : Sterile20 related proline-alanine-rich kinase (SPAK) and oxidative stress response kinase 1 ( OXSR1 ). Phosphorylation of SPAK's T loop located in its catalytic domain will activate SPAK, which will go on to phosphorylation the CCC's N-terminaldomain. Hence, WNK1 activates CCCs indirectly as an upstream regulator of SPAK/OSR1. In
3375-404: The DNA helix that produces a functional RNA molecule constitutes a gene. We define a gene as a DNA sequence that is transcribed. This definition includes genes that do not encode proteins (not all transcripts are messenger RNA). The definition normally excludes regions of the genome that control transcription but are not themselves transcribed. We will encounter some exceptions to our definition of
3450-450: The DNA sequence is used as a template for the production of an RNA molecule or a protein that performs some function. The emphasis on function is essential because there are stretches of DNA that produce non-functional transcripts and they do not qualify as genes. These include obvious examples such as transcribed pseudogenes as well as less obvious examples such as junk RNA produced as noise due to transcription errors. In order to qualify as
3525-766: The DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site. For example, enhancers increase transcription by binding an activator protein which then helps to recruit the RNA polymerase to the promoter; conversely silencers bind repressor proteins and make the DNA less available for RNA polymerase. The mature messenger RNA produced from protein-coding genes contains untranslated regions at both ends which contain binding sites for ribosomes , RNA-binding proteins , miRNA , as well as terminator , and start and stop codons . In addition, most eukaryotic open reading frames contain untranslated introns , which are removed and exons , which are connected together in
3600-514: The Mendelian gene or the molecular gene. The Mendelian gene is the classical gene of genetics and it refers to any heritable trait. This is the gene described in The Selfish Gene . More thorough discussions of this version of a gene can be found in the articles Genetics and Gene-centered view of evolution . The molecular gene definition is more commonly used across biochemistry, molecular biology, and most of genetics —
3675-499: The PCT than the DCT lumen because the PCT has a brush border (microvilli). DCT can be recognized by its numerous mitochondria (even though it is not as much as PCT), basal enfoldings and lateral membrane interdigitations with neighboring cells. The point where DCT contacts the cortical thick ascending limb of the loop of Henle is called macula densa . It has tightly packed columnar cells which display reversed polarity and may monitor
3750-414: The actions of extracellular signal–regulated kinases (ERK1 and ERK2) that lead to lysomal degradation. The NKCC1/2 cotransporters are regulated by intracellular Cl concentration. Studies point to WNK1 as key effector that couples Cl concentration to NKCC1/2 function. In hypertonic (high extracellular Cl ) conditions that trigger cell shrinkage, an unknown mechanism upregulates WNK1 expression to counteract
3825-433: The adenines of one strand are paired with the thymines of the other strand, and so on. Due to the chemical composition of the pentose residues of the bases, DNA strands have directionality. One end of a DNA polymer contains an exposed hydroxyl group on the deoxyribose ; this is known as the 3' end of the molecule. The other end contains an exposed phosphate group; this is the 5' end . The two strands of
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#17328011916863900-402: The complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products. This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions. The existence of discrete inheritable units
3975-524: The distinction between a heterozygote and homozygote , and the phenomenon of discontinuous inheritance. Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance , which suggested that each parent contributed fluids to the fertilization process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis , from Greek pan ("all, whole") and genesis ("birth") / genos ("origin"). Darwin used
4050-410: The early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities arranged like beads on a string. The experiments of Benzer using mutants defective in the rII region of bacteriophage T4 (1955–1959) showed that individual genes have a simple linear structure and are likely to be equivalent to a linear section of DNA. Collectively, this body of research established
4125-496: The efflux of K and Cl ions and cause the flow of water out of the cell to combat swelling. In the mature brain, the GABA neurotransmitter represents the major inhibitory signal used in neuronal signaling. GABA activates the GABA A receptor which is a Cl ion channel. Cl ions will enter the neuron causing hyperpolarization and inhibition of signaling. During brain development however, GABA A activation will allow Cl ions to leave
4200-522: The fact that both protein-coding genes and noncoding genes have been known for more than 50 years, there are still a number of textbooks, websites, and scientific publications that define a gene as a DNA sequence that specifies a protein. In other words, the definition is restricted to protein-coding genes. Here is an example from a recent article in American Scientist. ... to truly assess the potential significance of de novo genes, we relied on
4275-413: The functional product. The discovery of introns in the 1970s meant that many eukaryotic genes were much larger than the size of the functional product would imply. Typical mammalian protein-coding genes, for example, are about 62,000 base pairs in length (transcribed region) and since there are about 20,000 of them they occupy about 35–40% of the mammalian genome (including the human genome). In spite of
4350-630: The gene that is described in terms of DNA sequence. There are many different definitions of this gene — some of which are misleading or incorrect. Very early work in the field that became molecular genetics suggested the concept that one gene makes one protein (originally 'one gene - one enzyme'). However, genes that produce repressor RNAs were proposed in the 1950s and by the 1960s, textbooks were using molecular gene definitions that included those that specified functional RNA molecules such as ribosomal RNA and tRNA (noncoding genes) as well as protein-coding genes. This idea of two kinds of genes
4425-421: The genome. The vast majority of organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar ( 2-deoxyribose ), a phosphate group, and one of the four bases adenine , cytosine , guanine , and thymine . Two chains of DNA twist around each other to form a DNA double helix with
4500-421: The genomes of complex multicellular organisms , including humans, contain an absolute majority of DNA without an identified function. This DNA has often been referred to as " junk DNA ". However, more recent analyses suggest that, although protein-coding DNA makes up barely 2% of the human genome , about 80% of the bases in the genome may be expressed, so the term "junk DNA" may be a misnomer. The structure of
4575-538: The interaction between WNK1 and Cullin3, which is in a complex containing an E3 ubiquitin ligase that attaches the ubiquitin molecules to WNK1. The ubiquitinated WNK1 will subsequently undergo proteasomal degradation. WNK1 has mutations associated with Gordon hyperkalemia-hypertension syndrome ( pseudohypoaldosteronism Type II, featuring hypertension also called familial hyperkalemic hypertension (FHHt) ) and congenital sensory neuropathy ( HSAN Type II, featuring loss of perception to pain , touch , and heat due to
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#17328011916864650-421: The neuron causing the neuron to depolarize. Thus, GABA is an excitatory neurotransmitter during development. WNK1 has been implicated in the developmental switch from excitatory to inhibitory GABA signaling via interaction with NKCC1 and KCCs. WNK1 phosphorylates SPAK/OSR1 which then phosphorylates KCC2 inhibiting the flow of Cl ions out of the cell during development. The concentrations of Cl ions and K ion play
4725-413: The nucleus. Splicing, followed by CPA, generate the final mature mRNA , which encodes the protein or RNA product. Many noncoding genes in eukaryotes have different transcription termination mechanisms and they do not have poly(A) tails. Many prokaryotic genes are organized into operons , with multiple protein-coding sequences that are transcribed as a unit. The genes in an operon are transcribed as
4800-431: The phosphate–sugar backbone spiralling around the outside, and the bases pointing inward with adenine base pairing to thymine and guanine to cytosine. The specificity of base pairing occurs because adenine and thymine align to form two hydrogen bonds , whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must, therefore, be complementary , with their sequence of bases matching such that
4875-407: The serum-and glucocorticoid-inducible protein kinase SGK1 , leading to increased expression of the epithelial sodium channel (ENaC), which also promotes sodium re absorption. WNK1 regulates potassium channels found in the cortical collecting duct (CCD) and connecting tubule (CNT). Renal outer medullar potassium 1 ( ROMK1 ) and l arge conductance calcium-activated potassium channel (BKCa) are
4950-467: The strand of DNA like a train on a monorail, transcribing it into its messenger RNA form. This point brings us to our second important criterion: A true gene is one that is both transcribed and translated. That is, a true gene is first used as a template to make transient messenger RNA, which is then translated into a protein. This restricted definition is so common that it has spawned many recent articles that criticize this "standard definition" and call for
5025-461: The sugar ribose rather than deoxyribose . RNA also contains the base uracil in place of thymine . RNA molecules are less stable than DNA and are typically single-stranded. Genes that encode proteins are composed of a series of three- nucleotide sequences called codons , which serve as the "words" in the genetic "language". The genetic code specifies the correspondence during protein translation between codons and amino acids . The genetic code
5100-445: The synthesis of a protein. The transmission of genes to an organism's offspring , is the basis of the inheritance of phenotypic traits from one generation to the next. These genes make up different DNA sequences, together called a genotype , that is specific to every given individual, within the gene pool of the population of a given species . The genotype, along with environmental and developmental factors, ultimately determines
5175-809: The term gemmule to describe hypothetical particles that would mix during reproduction. Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries , Carl Correns , and Erich von Tschermak , who (claimed to have) reached similar conclusions in their own research. Specifically, in 1889, Hugo de Vries published his book Intracellular Pangenesis , in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes" ( Pangens in German), after Darwin's 1868 pangenesis theory. Twenty years later, in 1909, Wilhelm Johannsen introduced
5250-436: The term gene , he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured Wilhelm Johannsen 's distinction between genotype (the genetic material of an organism) and phenotype (the observable traits of that organism). Mendel was also the first to demonstrate independent assortment , the distinction between dominant and recessive traits,
5325-412: The term "gene" (inspired by the ancient Greek : γόνος, gonos , meaning offspring and procreation) and, in 1906, William Bateson , that of " genetics " while Eduard Strasburger , among others, still used the term "pangene" for the fundamental physical and functional unit of heredity. Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid (DNA)
5400-514: The two primary channels for potassium secretion. WNK1 indirectly stimulates clathrin-dependent endocytosis of ROMK1 by a potential interaction with intersectin (ITSN1); thus, kinase activity is not needed. Another possible mechanism of ROMK1 regulation is via autosomal recessive hypercholesterolemia (ACH), which is a clathrin adaptor molecule. ACH phosphorylation by WNK1 promotes the translocation of ROMK1 to clathrin coated pits triggering endocytosis . WNK1 may indirectly activate BKCa by inhibiting
5475-533: The volume loss. The increased WNK1 leads to activation of SPAK/OSR1 that activate NKCC1/2 via subsequent phosphorylation. NKCC1/2 will promote the influx of Na, K, and Cl ions into the cell thereby causing the flow of water into the cell. In the reverse circumstances, where hypotonic (low extracellular Cl ) conditions induce cell swelling, WNK1 is inhibited. Another cotransporter, KCC is inactive when phosphorylated; without activated WNK1, KCC does not undergo phosphorylation and can activate. The cotransporter will promote
5550-450: Was first suggested by Gregor Mendel (1822–1884). From 1857 to 1864, in Brno , Austrian Empire (today's Czech Republic), he studied inheritance patterns in 8000 common edible pea plants , tracking distinct traits from parent to offspring. He described these mathematically as 2 combinations where n is the number of differing characteristics in the original peas. Although he did not use
5625-430: Was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s. The structure of DNA was studied by Rosalind Franklin and Maurice Wilkins using X-ray crystallography , which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication. In
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