In 1866, Mendel's Principles of Heredity was published, complementing Darwin's theory of evolution. The molecular mechanism remained a mystery until 1953 when Crick and Watson discovered the structure of DNA, with crucial uncredited help from Rosalind Franklin. When they published the structure then it was not clear that DNA was the molecule of heredity. They speculated that "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible  copying  mechanism for the genetic material". 

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The project to  map the human genome from 1990 to 2003 was the catalyst for a revolution in the understanding of the molecular mechanism of inheritance and disease. It also produced rapid and low cost testing for probing  the critical segments of the genome. 

 

Geography of Chromosome 

In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. Each chromosome is made up of DNA tightly coiled many times around proteins called histones that support its structure.

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Chromosomes are not visible in the cell’s nucleus—not even under a microscope—when the cell is not dividing. However, the DNA that makes up chromosomes becomes more tightly packed during cell division and is then visible under a microscope. Most of what researchers know about chromosomes was learned by observing chromosomes during cell division.

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Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.”  The location of the centromere on each chromosome gives the chromosome its characteristic shape, and can be used to help describe the location of specific genes.

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In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46. So, for each homologous pair of chromosomes in your genome, one of the homologues comes from your mom and the other from your dad. Twenty-two of these pairs, called autosomes, look the same in both males and females. The 23rd pair, the sex chromosomes, differ between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome.

Here’s how egg and sperm are produced:

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• A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization.

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• The parent cell first copies each chromosome, leaving the duplicate pairs attached to one another.

   

• Producing eggs and sperm is our first opportunity for mixing and matching genes. When the mother makes an egg, her chromosomes first find their matched partners and exchange some DNA with each other. That’s called recombination. Because of this shuffling, genes from the mother’s mom and genes from the mother’s father can wind up next to one another on the same stretch of DNA. (The same thing happens in the father’s sperm.)

 

• Only after chromosomes recombine do they segregate into different egg cells, so that each egg cell ends up with one version of each chromosome.​

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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 the aging process.
 

The error rate in eukaryotic cells can be as low as 10−8 per nucleotide per replication,[83][84] whereas for some RNA viruses it can be as high as 10−3.[85] This means that each generation, each human genome accumulates 1–2 new mutations. If it takes roughly 10  M  years for a new species, and a generation lasts 10 years. There are 1-2 M DNA differences between nearest species. 

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Atavism is the reappearance of a trait that had been lost during evolution. Our genes do not determine who we are, but with atavism, they can sometimes serve as reminders of our evolutionary past. Hens do not have teeth, and humans do not have tails. Research suggests we have "what it takes" for a tail, and hens, indeed, have the genes that encode for a toothy grin; however, only in very rare situations do these traits manifest themselves as a phenotype. Atavism suggests that switching off gene expression is an important component to evolution.​

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Geography of a gene

A gene is the basic physical and functional unit of heredity. Genes are made up of DNA.

Some genes act as instructions to make molecules called proteins. However, many genes do not code for proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. An international research effort called the Human Genome Project, which worked to determine the sequence of the human genome and identify the genes that it contains, estimated that humans have between 20,000 and 25,000 genes.  

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There are two types of molecular genes: protein-coding genes and noncoding genes.[3][4][5][6]

During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function.  Most biological traits are under the influence of polygenes (many different genes) as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or the number of limbs, and some are not, such as blood type, the risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

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The region of the chromosome at which a particular gene is located is called its locus. The chromosomal or genomic location of a gene or any other genetic element is called a locus (plural: loci) and alternative DNA sequences at a locus are called alleles. Each locus contains one allele of a gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence.

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Sets of three nucleotides, known as codons, each correspond to a specific amino acid.[46]: 6  The principle that three sequential bases of DNA code for each amino acid was demonstrated in 1961. There are 64 possible codons (four possible nucleotides at each of three positions, hence 43 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.

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All genes are associated with regulatory sequences that are required for their expression. First, genes require a promoter sequence. Transcription begins at the promoter when RNA polymerase, an enzyme that facilitates transcription of DNA into mRNA, binds to a promoter, unwinds the helical structure of the DNA, and uses the single-stranded DNA as a template to synthesize RNA.[1] Once RNA polymerase reaches the termination signal, transcription is terminated.  A promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand). Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism.

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​Every person has a combination of  two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.

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Alleles at a locus may be dominant or recessive; dominant alleles give rise to their corresponding phenotypes when paired with any other allele for the same trait, whereas recessive alleles give rise to their corresponding phenotype only when paired with another copy of the same allele. If you know the genotypes of the organisms, you can determine which alleles are dominant and which are recessive. For example, if the allele specifying tall stems in pea plants is dominant over the allele specifying short stems, then pea plants that inherit one tall allele from one parent and one short allele from the other parent will also have tall stems.

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DNA profiles

 

The first DNA comparison test uses Short Tandem Repeat (STR) analyst: First, a DNA sample undergoes polymerase chain reaction with 20 primers targeting certain loci or  STRs (which vary in lengths between individuals and their alleles). The resultant fragments are separated by size (such as electrophoresis).[20]  The fragments create the characteristic  separate  bars. 

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SNP genotyping is the measurement of genetic variations of single nucleotide polymorphisms (SNPs) between members of a species.  More than 600 million SNPs have been identified across the human genome in the world's population.[19] A typical genome differs from the reference human genome at 4 to 5 million sites, most of which (more than 99.9%) consist of SNPs and short indels.

 

SNPs are one of the most common types of genetic variation. An SNP is a single base pair mutation at a specific locus, usually consisting of two alleles (where the rare allele frequency is > 1%). SNPs are found to be involved in the etiology of many human diseases and are becoming of particular interest in pharmacogenetics. SNPs are conserved during evolution. SNPs can also provide a genetic fingerprint for use in identity testing.

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In high-density oligonucleotide SNP arrays, hundreds of thousands of probes are arrayed on a small chip, allowing for many SNPs to be interrogated simultaneously. Although oligonucleotide microarrays have a comparatively lower specificity and sensitivity, the scale of SNPs that can be interrogated is a major benefit.

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

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Ancestry uses Quest diagnostics DNA service. The DNA test uses microarray-based autosomal DNA testing, analyzing as many as 700,000 changes in an individual’s genome. These changes (or variations) are called single-nucleotide polymorphisms, or SNPs for short. They are useful in identifying a person’s true ethnicity and can distinguish possible relatives from among people who have previously taken the AncestryDNA test. The Affymetrix Human SNP 5.0 GeneChip performs a genome-wide assay that can genotype over 500,000 human SNPs (Affymetrix 2007).

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Jumping genes 

Transposable elements make up a large fraction of the genome and are responsible for much of the mass of DNA in a eukaryotic cell. Although TEs are selfish genetic elements, many are important in genome function and evolution.[5] Transposons are also very useful to researchers as a means to alter DNA inside a living organism.

 

A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transposition is responsible for some diseases such as Hemophilia skipping generations. 

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Fifty percent of the DNA in each human cell is in the form of mobile jumping genes—strands of DNA called transposable elements (TE) that have the ability to sew themselves in and out of DNA as well as move to different sections and to place copies in different sections. The mobile strands of DNA in the jumping gene can create new types of proteins, disrupt the entire genetic process and provide new sources of regulation of DNA through many kinds of RNA effects. The jumping gene can provide new epigenetic changes, as well. Previous posts noted that these jumping genes and alternative messenger RNA splicing are especially critical for the human brain and its evolution.

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mRNA transposition in humans is 98% of the jumping genes, representing almost half of the entire human DNA. Recent dramatic findings show that jumping genes are very active in the brain. These SINEs and LINEs are actively altering and regulating neurons and other cells. Some of the changes have been incorporated into day-to-day functions. There is strong evidence that these jumping genes and their effects on alternative functions have been significant in the development of the human brain. This goes along with the evidence that the human brain uses the most alternative messenger RNA splicing. While these findings are still too complex to fully understand, it does appear to be part of the picture that has developed where jumping genes and cellular defense against them are crucial for evolution in general and especially so for the evolution of the human brain.

https://jonlieffmd.com/blog/jumping-genes-regulation-of-the-brain

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There is a growing understanding that transposing segments of DNA are responsible for some of the big changes in functionality between species, rather than random individual SNP's.  Atavism, the occasional expression of long lost features such as tails, suggests that switching off gene expression without loosing the function is an important part of evolution. Its easier to imagine that happening by moving a block of DNA rather than a random SNP mutation in the  promoter header. Dominant and recessive genes are another example of the switching on/off of gene expression. 4 chamber hearts as 2 atrium & ventricle pairs, or stomachs in ruminants could be examples of repeat block expressions. 

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Its easy to imagine that incremental changes in the length of bones is a result of single mutations producing a progressive response to environmental pressure. Step changes in functionality that require multiple coordinated changes  such as from marsupial to placental birth are more difficult to see as a result of  isolated single mutations. 

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