Tyrosine is produced from phenylalanine, so if the diet is deficient in phenylalanine, tyrosine will be required as well. The essential amino acids are arginine required for the young, but not for adults , histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. These amino acids are required in the diet. Plants, of course, must be able to make all the amino acids. Humans, on the other hand, do not have all the the enzymes required for the biosynthesis of all of the amino acids.
Why learn these structures and properties? It is critical that all students of the life sciences know well the structure and chemistry of the amino acids and other building blocks of biological molecules. Inspecting more explicitly the top and bottom quartiles of the diversity distributions at different positions, we found the skew in the substitution patterns to be even more pronounced.
We tested the HIV envelope gp, an exposed glycoprotein on the surface of the HIV envelope which is essential to virus entry into cells. It is therefore a likely subject for strong evolutionary constraints. At the same time, gp is a prominent antigen that undergoes rapid adaptation to evade the immune system 13 , It is thus an ideal showcase of a protein sequence comprised of amino acid positions that are highly conserved and others that are hypervariable.
The analysis was performed on a dataset of gp sequences 2 see Methods. Similarly, to the observations from the data set of vertebrate conservation Fig. The distributions are represented by a box plot overlaying a violin plot. As our final example of the different substitution patterns of serine in diversifying and conserved positions, we considered both the somatic and germline substitution patterns in B cell receptors. Let us first give a short introduction of this system to state the foundation for B cell receptors as a model of evolutionary selection process, emphasizing the special nature of somatic B cell receptor diversification.
The somatic selection process is especially informative as we can elucidate its germline source and thus track not only substitution patterns but also, and uniquely, their amino acid source. B cells undergo two stages of differentiation and selection of their B cell receptors. Both stages are essential for the creation of a varied immune repertoire to recognize and fight diseases.
In the first stage, B cells located in the bone marrow recombine germline V D and J gene segments 3 , 5 , 6 to create heavy and light chains which, when joined, form a unique B cell receptor 3 , 6 , 7 , B cells that form a functional receptor in this fashion are selected and proliferate, producing B cell clones, each with a common progenitor and a common receptor type.
During the immune response, the naive B cell population undergoes an additional process of affinity maturation. B cells proliferate, rapidly mutate their B cell receptor genes and die, such that the B cells with B cell receptors of higher binding to the antigens of the disease dominate the B cell population.
Since most of the human V, D, and J germline gene segments that recombine to encode the B cell receptor are known 7 , 16 , we are able to assign every observed mutant B cell receptor sequence to its germline origin. In this way, we can identify clonotypes of sets of mutant B cells with common progenitors and characterize the precise types of surviving substitutions along with their amino acid sources.
Moreover, we can determine for every amino acid in a sequence if it is germline encoded or the result of a somatic substitution during an immune response.
The CDRs interact with antigens and therefore need to rapidly adapt and diversify and are thus under diversifying selection 10 , 18 , 19 , On the other hand, the FWRs serve as the backbones of the receptor. As such, these regions are constrained to maintain the rigidly of their structure, and thus are mostly under purifying selection 10 , 18 , We analyzed the B cell repertoires of 40 human individuals from three different geographical location across the globe 10 , 22 , 23 , 24 see Methods.
For each individual we characterized the full set of heavy chain sequences belonging to the B cell receptor populations. The repertoires of sequences were divided into clones, as described above and see Methods. Focusing on the V gene segment of the B cell receptor, whose germline is clearly defined, we annotated the unique positions in each clone which had either undergone an amino acid substitution or remained encoded for their germline amino acids. Such positions were divided according to their positions into those found in the hypervariable CDRs and the conserved FWRs 8 , 20 , This test is based on the notion that as FWR regions by and large do not show substitutions.
We found that in the somatic substitution as well, the same pattern holds. We hypothesized that the tendency of phosphorserine substitution will be biased according to the type of serine encoding sets In all eukaryotes, serine S , threonine T and tyrosine Y are the only amino acids that can be modified by kinases. The ExAC dataset aggregates exome polymorphic sites of 60, unrelated healthy individuals. Altogether about 8. We mapped on the ExAC coding exomes 37, experimentally observed phosphorylated sites, among them 30, are phosphoserine see Methods.
To this end, we first built a substitution model that is based on the neutral model from all reported ExAC variations affecting the third position of the 4-fold degenerate amino acid codons covers valine, proline, threonine, alanine and glycine, see Methods and Sup. Looking across all phosphorylation sites, we compared the observed substitutions following single point mutations to the expected pattern of the 4-fold degenerate model. As seen in Fig.
When we extended our analysis to all single point mutations in any appearance of S, T and Y across the ExAC, we found that in contrast to our observation regarding the unique bias of functional p-S sites, the substitutions patterns of single point mutations could be primarily explained by the 4-fold degenerate model of mutations Fig.
Serine phosphorylation sites show differences in conservation depending on codon usage. Substitution network based on single point mutations based on the aggregation of human population polymorphism from the ExAC database. The tendency of substitution for S, T and Y for all phosphorylated positions Top. All S, T and Y sites in the human proteome Bottom.
Arrows indicate the substitution directionality. The color of the arrow captures the relative abundance of the substitutions compared to the expected patterns of mutation as calculated directly from the mutations in the third codon positions of 4-fold degenerate amino acids. Values are rounded to show the log power of the substitution abundance. The exact range of the relative abundance of all substitutions from S, Y and T to any other amino acid is shown next to the network view.
In the results above we have characterized patterns of substitution of serine both at the whole genome level under long-range evolution comparing the human genome to 99 other species, and at the human population level, analyzing protein substitutions from over 60, healthy individuals. We further tested our hypothesis by focusing on two specific biological contexts, the somatic changes for B-cell receptors and gp an envelop gene of HIV.
In both contexts, the genes include in single polypeptide chain distinguishable regions that are subjected to diversifying positive selection and other regions subjected to strong evolutionary constraints purifying selection.
Across all our examined datasets, we found a clear segregation of amino acid substitutions that are predicted by the division of serine encoding according to the genetic code. We show that the bias in serine codon usage previously found in B cell receptor repertoires 29 has a role in maintaining diversity beyond the immune B cell receptor repertoire.
Indeed, it underlies a more general segregation in amino acid substitution patterns that divides serine substitution into two groups linked to the diversity and functionality of gene products. We showed that while the majority of the phosphorylation sites in the human proteome are p-S We have thus shown that in biological selection processes the codons of serine indicate different types of selection for the amino acid and its permissible substitutions.
We have shown the importance of this special characteristic of serine, in general and for phosphorylation sites, across multiple scales of evolutionary selection: across species, within human population and for the somatic B cell selection and viral quasi species.
In this way we show that codon usage and not just amino acid type serves as an indicator of selection. We provide a further support for the view that the genetic code has evolved to allow maintenance of several types of substitution patterns.
All , known canonical exon gene sequences of all isoforms from the multiple alignments of 99 vertebrate genomes with human dataset were obtained from the UCSC Genome Browser database 9 , 13 , For each gene isoform in the data set, the diversity of amino acids was calculated at each position. In order to avoid bias of highly abundant or rare amino acids, the measurements were taken with an order of one The calculated per position diversity was used to estimate the meaningful types of amino acids found at each position.
At each position, only the n most abundant types of amino acids were included, where n is the amino acid diversity at that position. We defined meaningfully present serine positions as those in which serine was one of its n most abundant amino acids 10 , Amino acids and proteins are the building blocks of life.
When proteins are digested or broken down, amino acids are left. The human body uses amino acids to make proteins to help the body:. Nonessential means that our bodies can produce the amino acid, even if we do not get it from the food we eat.
Nonessential amino acids include: alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine. You do not need to eat essential and nonessential amino acids at every meal, but getting a balance of them over the whole day is important.
Attaches amino acids together to form a peptide. The peptide bond is repeated many times to create polypeptide chains which comprise the basic structure of all proteins. Primary Structure 1 0 :. A particular linear sequence of amino acids unique to each protein. All share the following characteristics:. These amino acids are referred to as residues. Therefore, for a large protein, charge and polarity are determined by the side chains on the residues.
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