Tag Archives: Genetics and Development

February 3, 1857 (a Tuesday)

Wilhelm Ludvig Johannsen

On this date, the Danish botanist and geneticist Wilhelm Ludvig Johannsen was born. His experiments in plant heredity offered strong support to the mutation theory of the Dutch botanist Hugo de Vries (that changes in heredity come about through sudden, discrete changes of the heredity units in germ cells). Many geneticists thought Johannsen’s ideas dealt a severe blow to Charles Darwin’s theory that new species were produced by the slow process of natural selection.

Johannsen explained his ideas in his book entitled On Heredity and Variation (1896), which he revised and lengthened with the rediscovery of Gregor Mendel’s laws and reissued as The Elements of Heredity in 1905. The enlarged German edition of this work was published in 1909 and became the most influential book on genetics in Europe. In it, Johannsen coined the terms “gene”, “phenotype”, and “genotype”.

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January 26, 1792 (a Thursday)

Robert Brown as a young man.

On this date, the Scottish botanist Robert Brown read his first scientific paper entitled “The botanical history of Angus“, to the Edinburgh Natural History Society, although it was never published in print in his lifetime.  He was born on 21 December 1773, so that he was but a little over eighteen when he read this essay.  Later in life, he made important contributions to science largely through his pioneering use of the microscope.

In 1827, while examining pollen grains under a microscope, Brown observed minute particles within vacuoles in the pollen grains executing a continuous jittery motion. He then observed the same motion in particles of dust, enabling him to rule out the hypothesis that the effect was due to pollen being alive. Although Brown did not provide a theory to explain the motion, and Jan Ingenhousz already had reported a similar effect using charcoal particles in German and French publications of 1784 and 1785, the phenomenon is now known as “Brownian motion.”  [In 1905, Albert Einstein postulated that Brownian motion was direct evidence of molecular action, thus supporting the atomic theory of matter.]

The cell.

Robert Brown is perhaps most famous for identifying a structure within cells that he named the “nucleus” in a paper read to the Linnean Society of London  in 1831 and published in 1833. Furthermore, he suggested that the nucleus may be an essential component of the cell. He discovered the nucleus while studying orchids microscopically, in the cells of the flower’s outer layer. The nucleus had been observed before, perhaps as early as 1682 by the Dutch microscopist Leeuwenhoek, and Franz Bauer had noted and drawn it as a regular feature of plant cells in 1802, but it was Brown who gave it the name it bears to this day (while giving credit to Bauer’s drawings). Neither Bauer nor Brown thought the nucleus to be universal, and Brown thought it to be primarily confined to Monocotyledons.

January 17, 1834 (a Friday)

August Weismann

On this date, the German biologist August (Friedrich Leopold) Weismann was born in Frankfurt. Ernst Mayr ranked him the second most notable evolutionary theorist of the 19th century, after Charles Darwin. Weismann was one of the founders of modern genetics, who is best known for his opposition to the concept of the inheritance of acquired traits and for his “germ plasm” theory, the forerunner of DNA theory.

During his career, Weismann grappled with Christian creationism as a possible alternative to evolutionary theory. In his work Über die Berechtigung der Darwin’schen Theorie (On the Justification of the Darwinian Theory) published in 1868, he compared creationism and evolutionary theory, concluding that many biological facts can be seamlessly accommodated within evolutionary theory but remain puzzling if considered the result of acts of creation. After he completed this work, Weismann accepted evolution as a fact on a par with the fundamental assumptions of astronomy (e.g., heliocentrism).

In a lecture in 1883 entitled “On inheritance” (“Über die Vererbung”), Weismann proposed the so-called germ-plasm theory of heredity. This theory states that a multicellular organism’s cells are divided into somatic cells (the cells that make up the body) and germ cells (cells that produce the gametes).  His great insight was to see that the two do not exchange information – variation must be produced in the germ cells. In other words, genetic information cannot pass from somatic cells to germ cells and on to the next generation. This was referred to as the Weismann barrier.  In addition, the germ cells are neither influenced by environmental conditions nor by learning or morphological changes that happen during the lifetime of an organism, which information is lost after each generation.  Thus, the germ-plasm theory ruled out the inheritance of acquired characteristics as proposed by Jean-Baptiste Lamarck.  In stating definitely seven years later that the material of heredity was in the chromosomes, Weismann anticipated the chromosomal basis of inheritance.

In October 1887, Weismann began the famous experiment of chopping off the tails of fifteen hundred white mice, repeatedly over 20 generations. He subsequently reported that no mouse was ever born in consequence without a tail, stating that:

901 young were produced by five generations of artificially mutilated parents and yet there was not a single example of a rudimentary tail or any other abnormality of the organ.

Weismann knew that it might be objected that the number of generations had been far too small:

Hence the experiments on mice, when taken alone, do not constitute a complete disproof of [inheritance of acquired characteristics]: they would have to be continued to infinity before we could maintain with certainty that hereditary transmission cannot take place. But it must be remembered that all the so-called proofs which have hitherto been brought forward in favour of the transmission of mutilations assert the transmission of a single mutilation which at once became visible in the following generation. Furthermore the mutilation was only inflicted upon one of the parents, not upon both, as in my experiments with mice. Hence, contrasted with these experiments, all such ‘proofs’ collapse; they must all depend on error.

Weismann made it clear that he embarked on the experiment precisely because, at the time, there were many claims of animals inheriting mutilations (he refers to a claim regarding a cat that had lost its tail having numerous tail-less offspring). There were also claims of Jews born without foreskins. None of these claims, he said, were backed up by reliable evidence that the parent had in fact been mutilated, leaving the perfectly plausible possibility that the modified offspring were the result of a mutated gene. The purpose of Weismann’s experiment was to lay the claims of inherited mutilation to rest.  Its results were consistent with Weismann’s germ-plasm theory.

Mitosis and meiosis compared.

Meiosis was discovered and described for the first time in sea urchin eggs in 1876, by noted German biologist Oscar Hertwig (1849-1922). It was described again in 1883, at the level of chromosomes, by Belgian zoologist Edouard Van Beneden (1846-1910) in Ascaris worms’ eggs. However, the significance of meiosis for reproduction and inheritance was grasped only in 1890 by Weismann, who noted that two cell divisions were necessary to transform one diploid cell into four haploid cells in order to maintain the correct number of chromosomes in the offspring.

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December 21, 1889 (a Saturday)

Sewall Wright

Sewall Wright

On this date, the American mathematician and biologist Sewall Green Wright (he later dropped the middle name) was born. He was one of the founders, along with R. A. Fisher and J. B. S. Haldane, of modern theoretical population genetics. He researched the effects of inbreeding and crossbreeding with guinea pigs and, later on, the effects of gene action on inherited characteristics. The synthetic theory of evolution as described by Sewall Wright synthesizes (combines) the principles of natural selection outlined by Charles Darwin with the principles of genetics. Wright explained evolution in terms of changes in gene frequencies.

The classic example which supports this theory is that of the peppered moth in England. The moth can be either dark or light colored. Scientists have determined that body color in the peppered moth is controlled by a single gene with two alleles: the allele for dark body color is dominant and the allele for light body color is recessive. Prior to the industrialization of central England, the light-colored allele was most prevalent. The light-colored moths would hide on the white-barked trees and avoid bird predation. But the pollution generated by the new industries stained the light-colored trees dark. Gradually the light-colored moth was attacked and that allele became much less prevalent. In its place, the dark-colored allele became the most predominant allele because moths that carried that allele could camouflage themselves on the stained trees and avoid being eaten by their bird predators. Clearly the population had evolved to a better adaptive condition.

Wright is perhaps best known for his concept of genetic drift, formerly known as the “Sewall Wright effect.” Genetic drift results when small populations of a species are isolated and due to pure chance, the few individuals who carry certain relatively rare genes may fail to transmit them. The genes may therefore disappear and their loss may lead to the emergence of new species, although natural selection has played no part in the process. Genetic drift can be summarized as “bad luck, not bad genes.”

Wright had long been concerned with cases in which genes interacted in ways not predictable from their individual effects. He believed that evolutionary creativity often depended on putting together favorable combinations of genes that were individually deleterious. But natural selection will not ordinarily incorporate such genes in a large, sexually reproducing population. Wright’s answer was his “shifting balance theory“, which holds that the best opportunity for adaptive evolution lies in the population structure.

Wright thought that many, if not most, species were subdivided into small populations that exchanged only a few migrants with each other and thus were not completely isolated. Because of the small size of each of these populations, genetic drift would have a significant effect on the genetic composition of each, thus allowing the populations to differentiate genetically by an appreciable amount. In this way, each of the populations would act as a small experiment in evolution.

Wright’s shifting balance theory consists of three distinct phases:

  • Phase 1, the exploratory phase, is characterized by the action of genetic drift in a local population. One or more may drift into an advantageous gene combination.
  • In phase 2, a new advantageous combination of genes is naturally selected in one or more populations.
  • Finally, in phase 3, those populations will then increase or, more likely, send out migrants to adjacent local populations, introducing the advantageous gene combination of the immigrants. As a result of this process, eventually all of the populations attain the favorable gene combination.

Although Wright’s theory remains controversial, it has been very popular and influential in the biological community. It is one of the things that biologists argue over. They do not argue over whether or not evolution occurs; that evolution occurs is a biological fact.

A Case of Correlation not Causation

ResearchBlogging.orgA scientific study entitled, “Multiple aspects of sexual orientation: Prevalence and sociodemographic correlates in a New Zealand national survey” recently appeared in the Archives of Sexual Behavior. The abstract was published online on 22 June 2010:

Sexual orientation consists of multiple components. This study investigated both sexual identity and same-sex sexual behavior. Data came from the New Zealand Mental Health Survey, a nationally representative community sample of New Zealanders aged 16 years or older, interviewed face-to-face (N = 12,992, 48% male). The response rate was 73.3%. Self-reported sexual identity was 98.0% heterosexual, 0.6% bisexual, 0.8% homosexual, 0.3% “Something else,” and 0.1% “Not sure.” Same-sex sexual behavior with a partner was more common: 3.2% reported same-sex sexual experience only and 1.9% reported both experience and a relationship. For analysis of childhood and lifecourse, five sexuality groups were investigated: homosexual, bisexual, and heterosexual divided into those with no same-sex sexual experience, experience only, and experience and relationship. The non-exclusively heterosexual groups were more likely to have experienced adverse events in childhood. Educational achievement and current equivalized household income did not differ systematically across the sexuality groups. Only 9.4% of the exclusively heterosexual lived alone, compared with 16.7% of bisexuals and 19.0% of homosexuals. Heterosexuals were more likely than bisexuals or homosexuals to have ever married or had biological children, with differences more marked for males than for females. Heterosexuals with no same-sex sexual experience were more likely to be currently married than the other two heterosexual groups. Restricting comparisons to heterosexual, bisexual, and homosexual identification ignores the diversity within heterosexuals. Differences between the bisexual and homosexual groups were small compared with the differences between these groups and the exclusively heterosexual group, except for sex (80.8% of bisexuals were female).

Of people who reported certain traumatic childhood events, including sexual assault, rape, violence to the child, and witnessing violence in the home, 15 percent were not heterosexual; of those without such experiences, only 5 percent were not heterosexual, suggesting that such experiences tripled the chance of later homosexual or bisexual identification. Although sexual or physical abuse in childhood was associated with adult homosexuality, other traumatic experiences, such as the sudden death of a loved one or serious childhood illness or accident, were only slightly associated with non-heterosexual identity or behavior.

The authors are J. Elisabeth Wells and Magnus A. McGee, who are both in the Department of Public Health and General Practice, University of Otago, New Zealand and Annette L. Beautrais, who is affiliated with both the Department of Psychological Medicine, University of Otago and the Department of Emergency Medicine, Yale University School of Medicine. The journal is peer-reviewed, so these authors are not hacks.

However, I find some aspects of the report disturbing because of their potential to mislead non-scientists (and even some scientists).

  • Wells, in commenting publicly about the study, revealed her assumption that homosexuals are made, not born. This is a major glaring flaw, since existing research has not produced conclusive findings indicating grounds for such an assumption. “People who either identify themselves as homosexual or bisexual, or have had a same-sex encounter or relationship, tend to come from more disturbed backgrounds,” she remarked. “You could say that if someone was sexually abused as a child, chooses to live as a homosexual and lives life well, then that is not a bad thing. But if they are living a homosexual life and regretting it, that is another matter.”
  • More importantly, I seriously doubt the credibility of this study because all of the ratios are way off. Of the sample who provided responses, ninety-eight percent identified as heterosexual, only 0.8 percent homosexual, and only 0.6 percent bisexual. Of those who identified as bisexual, 80 percent were women. This study is seriously skewed. The responses were all obtained in face-to-face interviews, which in sex studies are known to lead to under-reporting by sexual minorities. Self-reporting, even when obtained by questionnaire, is unreliable in sex studies. For example, homosexuals are probably less likely to identify as such because of homophobia in society. And are self-avowed homosexuals more — or less — likely to reveal that they were victims of child sex abuse than heterosexuals? They may be more comfortable talking about their sex lives and therefore more inclined to report childhood abuse. On the other hand, heterosexual males, less comfortable with discussing sex or seeing themselves as victims, may be far less likely to admit that they were sexually abused as children.
  • It is always important in scientific studies to distinguish between correlation and causation. This study reveals only a correlation between childhood abuse and later homosexual identification. It does not and, in fact, cannot demonstrate a causal connection — that child abuse causes homosexuality. To conclude so would be as illogical as saying that lynchings cause brown skin, or wearing skirts causes breast cancer. Perhaps homosexual identification causes child abuse — in other words, maybe homosexual children are more likely to be victims because of bigotry against them? Independent evidence — namely, the most comprehensive report ever on the experiences of lesbian, gay, bisexual and transgender (LGBT) students in the United States, The 2007 National School Climate Survey — indicates that this is likely. The survey of 6,209 middle and high school students conducted by the Gay, Lesbian, and Straight Education Network (GLSEN) found that nearly 9 out of 10 LGBT students (86.2 percent) experienced harassment at school in the past year, three-fifths (60.8 percent) felt unsafe at school because of their sexual orientation, and about a third (32.7 percent) skipped a day of school in the past month because of feeling unsafe. This survey, of course, did not address abuse in the home arising out of homosexual identification.

Homophobic bullying.

Tony Simpson, chairman of the national LGBT group Rainbow Wellington in New Zealand, said that the research should not be taken to mean that homosexuals are not born that way. “I have no doubt that the religious right will leap to the conclusion that this goes to show conclusively that homosexuals are made rather than born,” he said. As he predicted, the study was reported on LifeSiteNews.com, an antigay religious-right Web site.

However, the scientific and medical consensus is clear: homosexual orientation is not the result of choice. There is probably a combination of genetic and biological factors that cause people to become gay. Choice and willfulness have nothing to do with who is and is not homosexual (or heterosexual). Someone who falls in love with a member of their own sex has no more choice over their sexual orientation than someone who falls in love with a member of the opposite-sex. The only choice is whether to embrace and celebrate one’s orientation, or to be ashamed and hide.

Suggested Reading:

What’s a cell-adhesion protein like you doing in a unicellular organism like me?

ResearchBlogging.orgThe principle of common descent in evolutionary theory means that all living organisms are related to each other in a genealogical sense. In other words, many of the similarities between different organisms exist because they were inherited from a common ancestor with those features. Since inherited traits are encoded in the DNA of the organisms, comparisons of their genes is a way to infer descent from a common ancestor.

One of the similarities among all metazoans is their multicellularity, which requires proteins that enable cells to adhere and communicate. A number of cell adhesion and cell-cell signaling proteins do this in multicellular organisms, but only such proteins that exist in all (or nearly all) modern metazoans, but not in any other multicellular organisms such as fungi and plants, should have been present in the last common ancestor (LCA) of metazoans. The cadherin family of proteins apparently meets this criteria.

.Monosiga brevicollis

Cadherins have also been found in the choanoflagellates, which are unicellular and sometimes colony-forming organisms. Each cell has a single flagellum surrounded by a collar (choano comes from the Greek word for collar) of microvilli that it uses to swim and capture bacterial prey. As the flagellum beats, it draws water through the collar’s microvilli, which filter out bacteria and other tiny food particles. Choanoflagellates are nearly indistinguishable, in terms of shape and function, from the “collar cells” (choanocytes) of sponges, the simplest metazoans. The beating flagella of choanocytes generate a current that draws water and food particles through the body of the sponge, and their microvilli filter out food particles. Henry James-Clark first recognized this remarkable similarity over 130 years ago, which eventually led to the hypothesis that sponges, and, by implication, other animals, evolved from choanoflagellate-like ancestors.

To investigate this possibility, Abedin and King first examined the published genomes of a choanoflagellate, Monosiga brevicollis, and four diverse animals to identify cadherin genes in each. Surprisingly, despite the lack of obvious cell adhesion in M. brevicollis, its number of putative cadherin genes (23) is greater than the number of recognized cadherin genes in the fruitfly Drosophila melanogaster (17). Of the other animals they looked at, the mouse Mus musculus has the most cadherin genes (127), followed by the sea anemone Nematostella vectensis (46), and the sea squirt Ciona intestinalis (32). When compared as a percentage of the total number of genes in each genome, cadherins are more common in M. brevicollis than in any of the four metazoans except M. musculus.

Cadherin.

The cadherin repeat is a repeating domain (functional subunit of a protein) found in all cadherin proteins, which enables them to adhere to each other and which depends on calcium ions (Ca+2) to function (cadherins are named after it). A cadherin protein typically consists of an extracellular region, a single membrane-spanning region, and a cytoplasmic region. The cadherin repeat is found in the extracellular region; surprisingly, in comparing the five organisms, Abedin and King discovered that the average number of extracellular cadherin repeats (ECs) in M. brevicollis is highest (14.7), while the average in M. musculus is lowest (5.2).

In the extracellular and cytoplasmic regions of different cadherin proteins, other distinctive domains can be found. The extracellular domains EGF and LamG are shared by M. Brevicollis, N. vectensis, and M. musculus, while the extracellular domains N-hh and IG and the cytoplasmic domain SH2 are shared by M. brevicollis and N. vectensis. This suggests that these domains were present in the LCA of choanoflagellates and metazoans. A cytoplasmic domain called the classic cytoplasmic domain (CCD) is responsible for the ability of classic cadherin proteins (defined as those involved in cell-cell adherens junctions) to anchor, with the help of catenins, to the actin cytoskeleton. As a result, the actin cytoskeleton of one cell can be linked to the cadherins in the plasma membrane, which in turn attach through their extracellular regions to the cadherins in the neighboring cell membranes. However, since CCDs are found in N. vectensis and M. musculus but not in M. brevicollis, the CCD-containing cadherins probably evolved after the origin of the metazoans.

Given that Monosiga brevicollis leads a unicellular lifestyle and is not known to form cell-cell contacts, what are its putative cadherins doing? In an effort to answer this question, Abedin and King determined the locations in choanoflagellate cells of two nearly identical cadherin proteins, MBCDH1 and MBCDH2. Both of them resemble the inferred ancestral cadherin in having SH2 domains but not CCDs. The locations of polymerized actin in the cells were also determined. The experiments showed that actin, MBCDH1, and MBCDH2 proteins were localized together around the base of the choanoflagellate cell, where the choanoflagellate attaches to surfaces, and especially around the microvilli of the collar, where bacteria are captured and ingested. This implies that the associations between cadherins and actin filaments was present in the LCA of choanoflagellates and metazoans. But why?

The localization of these ancient cadherin proteins suggests that perhaps the choanoflagellate/metazoan LCA used them to bind and eat bacteria, while the multicellular metazoans adopted these proteins for gluing their cells together. Abedin and King support this hypothesis by pointing out that some pathogenic bacteria today bind to the extracellular region of metazoan cadherins, taking advantage of them to help invade the host cell. “Indeed, the transition to multicellularity likely rested on the co-option of diverse transmembrane and secreted proteins to new functions in intercellular signaling and adhesion,” they conclude in their report.

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