Mendel’s Peas
And Other Myths About Genetics
Gregor Mendel Was Not A Geneticist. He Was A
Failure.
His family was too poor to afford an education. Despite suffering from deep bouts
of depression that, more than once, caused him to temporarily abandon his
studies, Mendel graduated from the program in 1843.
He wanted to teach, but he failed his teaching exams twice (the second time
caused a nervous breakdown). He eventually got a job teaching high school. The
only reason we know about him at all is that he took really good notes on his peas.
He published, but no one cared. So he died unknown. Thirty years later three
scientists all rediscovered the same things he had. They all wanted credit, but
eventually gave it to Mendel.
Mendel made three laws for his peas.
The Law of Dominance - if two alleles (bits) are present in a zygote (egg) and one
of them is visible in the grown plant/person, then that is a dominant trait.
The Law of Separation - if you have one dominant and one recessive trait, they
will be separated when your egg/sperm/pollen is passed on.
The Law of Independent Assortment- no egg or sperm knows what any other egg
or sperm is doing. You get a mix.
We all remember the Punnett Squares
Some diseases follow Mendelian lines.
https://en.wikipedia.org/wiki/Mendelian_traits_in_humans
Haemophilia
Genetics of Cystic Fibrosis
Genetic traits that do not follow Mendelian lines.
https://en.wikipedia.org/wiki/Non-Mendelian_inheritance
But it’s not that simple.
Twenty-five years ago, a variant (p.Phe508del; also known as F508del in legacy
nomenclature) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
was found to be the most common cause of cystic fibrosis3-5….Almost 2,000 variants
have been reported to the Cystic Fibrosis Mutation Database, one of the first and most
successful locus-specific databases. Among these variants, 40% are predicted to cause
substitution of a single amino acid, 36% are expected to alter RNA processing (including
nonsense, frameshift and mis-splicing variants), 3% involve large rearrangements of
CFTR, and 1% affects promoter regions; 14% seem to be neutral variants, and the effect of
the remaining 6% is unclear. Disease causing variants can affect the quantity and/or
function of CFTR at the cell membrane (FIG 2). Historically, CFTR variants have been
grouped into five (and sometimes six) functional classes9
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364438/
Even “the royal disease” isn’t straightforward.
The genetic heterogeneity of hemophilia B was studied in 92 patients from 71 kindreds. Eighty patients
with factor IX activity <4% (severe or moderately severe hemophilia B) could be divided into four groups:
(1) 7 patients with greatly prolonged bovine thromboplastin times and normal levels of factor IX antigen
(measured by antibody neutralization of a human factor IX inhibitor and by electroimmunoassay with a
rabbit factor IX antiserum); (2) 17 patients with mildly prolonged bovine thromboplastin times and factor
IX antigen levels between about 25% and normal; (3) 8 patients with normal bovine thromboplastin
times and antigen levels between about 25% and normal; and (4) 48 patients with normal bovine
thromboplastin times and no measurable excess antigen. None of 12 patients with mild hemophilia B
(factor IX activity of 4%-22%) had a prolonged bovine thromboplastin time, although 4 patients had an
excess of factor IX antigen over activity.
https://www.researchgate.net/profile/Carol_Kasper/publication/22271256_Hemophilia_B_Characterization_of_genetic_variants_and_d
etection_of_carriers/links/54da62fd0cf233119bc333bc/Hemophilia-B-Characterization-of-genetic-variants-and-detection-of-carriers.pdf
Mendel knew this in his lifetime.
In an attempt to determine if his laws applied to animals, Mendel stayed in the garden and started working
with honeybees. A bad choice, considering that honeybee males are the products of unfertilized eggs, and
thus are haploid for every single chromosome...As it turns out, various forms of haploidy and other
weird-ploidy are fairly common in plants, animals, and elsewhere. The platypus, for example, carries
ten copies of its sex chromosomes for reasons that still aren't clear. Yeast will happily go through
life in a haploid state until given a chance to mate, at which point it will fuse with another haploid
cell, form a diploid, and continue on as if nothing else has changed, provided it's supplied with
enough nutrients. Bacteria are normally haploid, except that sections of the genome can sporadically be
transferred between individuals by viruses or through a process called conjunction (they also have circular
chromosomes, which caused early gene mappers
fits).https://arstechnica.com/science/2010/04/breaking-mendels-laws-the-value-of-informative-errors/2/
Genes have been mapped.
20 - 25k genes. https://www.genome.gov/12513430/2004-release-ihgsc-describes-finished-human-sequence
But genes aren’t set. One such model is Zea mays (maize), particularly those plants that produce
variably colored kernels. Because each kernel is an embryo produced from an individual fertilization,
hundreds of offspring can be scored on a single ear, making maize an ideal organism for genetic analysis.
Indeed, maize proved to be the perfect organism for the study of transposable elements (TEs), also
known as "jumping genes," which were discovered during the middle part of the twentieth century by
American scientist Barbara McClintock. McClintock's work was revolutionary in that it suggested that
an organism's genome is not a stationary entity, but rather is subject to alteration and
rearrangement-a concept that was met with criticism from the scientific community at the time. However,
the role of transposons eventually became widely appreciated, and McClintock was awarded the Nobel
Prize in 1983 in recognition of this and her many other contributions to the field of genetics.
https://www.nature.com/scitable/topicpage/barbara-mcclintock-and-the-discovery-of-jumping-34083/
Genes don’t turn themselves off or on.
Histones
histones can impact gene expression by altering chromatin structure or recruiting histone modifiers. Histone proteins act to package DNA,
which wraps around the eight histones, into chromosomes. https://www.whatisepigenetics.com/histone-modifications/ Epigenetics is the
covalent modification to DNA that impacts gene expression without affecting the underlying genetic sequence
Beyond Epigenetics
In the 19th century, August Weismann severed the tails of mice, observed no reduction in tail length among their offspring,
and declared Lamarckian inheritance refuted. Had he instead removed “teeth” from the amoeba Difflugia corona, he would
have found reliable inheritance of the disfigurement...In many complex animals, the germ line is separated from the rest of
the body early in development, which led Weismann to conclude that environmentally caused changes in an organism are
not inherited. A revelation in recent years, and the focus of Russell Bonduriansky and Troy Day’s admirable book, Extended
Heredity, is the finding that “Weismann’s barrier” is remarkably porous. Indeed, a vast multitude of nongenetic factors
(including symbionts, hormones, nutrients, antibodies, prions, and learned knowledge) can be passed from parents to
offspring...NGI also includes adaptive parental effects, social learning in animals, the inherited microbiome, and structural
inheritance in single-celled eukaryotes. These factors undertake important functions, including predicting adaptive
responses, finding fitness peaks, and preceding genetic
change.https://blogs.sciencemag.org/books/2018/06/26/extended-heredity/