Welcome to The Visible Embryo
The Visible Embryo Birth Spiral Navigation
Fetal Timeline--- -Maternal Timeline-----News-----Prescription Drugs in Pregnancy---- Pregnancy Calculator----Female Reproductive System

WHO International Clinical Trials Registry Platform

The World Health Organization (WHO) has a Web site to help researchers, doctors and patients obtain information on clinical trials.

Now you can search all such registers to identify clinical trial research around the world!




Pregnancy Timeline

Prescription Drug Effects on Pregnancy

Pregnancy Calculator

Female Reproductive System


Disclaimer: The Visible Embryo web site is provided for your general information only. The information contained on this site should not be treated as a substitute for medical, legal or other professional advice. Neither is The Visible Embryo responsible or liable for the contents of any websites of third parties which are listed on this site.

Content protected under a Creative Commons License.
No dirivative works may be made or used for commercial purposes.


Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development

Developmental biology - Human Evolution

Need for vitamin D may have increased breast density

During the last ice age, a mutation arose in northern China selecting for more mammary ducts in breasts...

During the last ice age, the critical role of breast feeding in human survival may have selected for a common gene mutation found in East Asians, and by extension of their migration across Beringia — into Native Americans. Surprisingly, it also affects the shape of teeth.

Clues came from a 2007 paper and later a 2015 study by Leslea Hlusko PhD, and coauthor Dennis O'Rourke PhD, in which the scientists deduced from DNA of Native Americans that they split from other Asian populations more than 25,000 years ago, even though arriving in North American only 15,000 years ago. The conclusion was that Native American ancestors settled for some 10,000 years in an area between Asia and North America before drifting into the New World. This so-called Beringian standstill coincides with the Last Glacial Maximum between 18,000 and 28,000 years ago.

According to the Beringian standstill hypothesis, as the climate became drier and cooler as the Last Ice Age began, people who had been living in Siberia moved into Beringia. Gigantic ice sheets to the east prohibited migration into North America. They couldn't migrate southwest because of a large expanse of a treeless and inhospitable tundra. The area where they found refuge was a biologically productive region thanks to newly altered ocean currents, and a landmass increased by lower sea levels. Genetic studies of animals and plants from Beringia suggest it was an isolated refuge, where species adapted new traits. Such isolation is ripe for selection of genetic variations (variants) making for easier survival by plants, animals and humans.

According to Leslea Hlusko PhD: "At that high latitude, these people would have been vitamin D deficient. We know they had a diet that was attempting to compensate for it from the archaeological record, and because there is evidence of selection in this population for specific alleles (copies) of genes that influence fatty acid synthesis. But even more specifically, these genes modulate the fatty acid composition of breast milk. It looks like this mutation of the EDAR gene was selected for in that ancestral population, and EDAR's effects on mammary glands is the most likely target of the selection."
The EDAR gene influences development of many structures derived from the fetal ectoderm, including tooth shape, sweat glands, sebaceous glands, mammary glands and hair. As a consequence, selection on one trait leads to coordinated evolution of the others. The late evolutionary biologist Steven Jay Gould referred to such byproducts of evolution as spandrels.

"This Beringian population is one example of what has happened thousands of times, over millions of years: Human populations form, exist for a little while and then disperse to form new populations, mixing with other groups of people, all of them leaving traces on modern human variation today. An important take-home message is that human variation today reflects this dynamic process of ephemeral populations, rather than the traditional concept of geographic races with distinct differences between them." According to Leslea Hlusko PhD and associate professor of Integrative Biology at University of California at Berkeley, California.

Arising about 20,000 years ago, this genetic mutation is on a gene called EDAR that codes for the protein ectodysplasin A receptor, and increases the density of the ducts branching through breast mammary glands. Such an increase would potentially provide more fat and vitamin D to nursing infants living far north where there is a scarcity of ultraviolet radiation from sunlight. We humans produce vitamin D through our skin's exposure to sunlight.

When a mutation occurs in at least one of EDAR's two copies (alleles), it also affects the density of sweat glands in our skin, the thickness of our hair shafts, and shoveling in our teeth. Previous gene analysis in living humans concluded the EDAR mutation arose in northern China selecting for more sweat (sebaceous) glands during the last ice age.

Shovel shaped incisors

However, Leslea Hlusko PhD, Associate Professor, Integrative Biology, University of California, Berkeley adds: "There are some really hot parts in the world, and if sweating was so sensitive to selective pressures, I can think of some places where we would have more likely seen selection on that genetic variation instead of in northern China during the Last Glacial Maximum."

If the spread of this genetic mutation is, in fact, due to selection for increased mammary ductal branching, this adaptation would be the first evidence of gene selection affecting the human maternal-infant bond.
"This highlights the importance of the mother-infant relationship and how essential it has been for human survival."

Leslea Hlusko PhD, Associate Professor, Integrative Biology, University of California at Berkeley (UCB), USA.

Hlusko specializes in the evolution of teeth among animals, in particular primates and early humans. She discovered these connections after being asked to participate in a scientific session on the dispersal of modern humans throughout the Americas at the February 2017 American Association for the Advancement of Science meeting. In preparing her talk on what teeth can tell us about the peopling of the New World, she pulled together the genetics of dental variation with the archaeological evidence to re-frame our understanding of selection on incisor shape.

For the study, Hlusko and her colleagues assessed the occurrence of shovel-shaped incisors in archeological populations in order to estimate the time and place of evolutionary selection for the trait. They found that nearly 100 percent of Native Americans prior to European colonization had shoveled incisors, as do approximately 40 percent of East Asians today.
The team then used genetic effects that are shared with dental variation as a way to discern the evolutionary history of mammary glands as they share a common developmental path.

Incisors are called "shovel-shaped" when the tongue-side of the incisors - the cutting teeth in the front of the mouth, four on top, four on the bottom - have ridges along the sides and biting edge. It is distinctive of Native Americans and populations in East Asia - Korea, Japan and northern China - with an increasing incidence as you travel farther north. Unconvinced by a previous idea that shoveled incisors were selected for their use in softening animal hides, Hiusko looked at explanations unrelated to teeth shape.

"People have long thought that this shoveling pattern is so strong that there must have been evolutionary selection favoring the trait, but why would there be such strong selection on the shape of your incisors?" Hlusko thought. "When you have shared genetic effects across the body, selection for one trait will result in everything else going along for the ride."
Understanding the origins of dense breast tissue could also have implications in breast cancer.

The frequency of the human-specific EDAR V370A isoform is highly elevated in North and East Asian populations. The gene is known to have several pleiotropic effects, among which are sweat gland density and ductal branching in the mammary gland. The former has led some geneticists to argue that the near-fixation of this allele was caused by selection for modulation of thermoregulatory sweating. We provide an alternative hypothesis, that selection instead acted on the allele’s effect of increasing ductal branching in the mammary gland, thereby amplifying the transfer of critical nutrients to infants via mother’s milk. This is likely to have occurred during the Last Glacial Maximum when a human population was genetically isolated in the high-latitude environment of the Beringia.

Because of the ubiquitous adaptability of our material culture, some human populations have occupied extreme environments that intensified selection on existing genomic variation. By 32,000 years ago, people were living in Arctic Beringia, and during the Last Glacial Maximum (LGM; 28,000–18,000 y ago), they likely persisted in the Beringian refugium. Such high latitudes provide only very low levels of UV radiation, and can thereby lead to dangerously low levels of biosynthesized vitamin D. The physiological effects of vitamin D deficiency range from reduced dietary absorption of calcium to a compromised immune system and modified adipose tissue function. The ectodysplasin A receptor (EDAR) gene has a range of pleiotropic effects, including sweat gland density, incisor shoveling, and mammary gland ductal branching. The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago. The dental pleiotropic effects of this allele suggest an even higher occurrence among indigenous people in the Western Hemisphere before European colonization. We hypothesize that selection on EDAR V370A occurred in the Beringian refugium because it increases mammary ductal branching, and thereby may amplify the transfer of critical nutrients in vitamin D-deficient conditions to infants via mothers’ milk. This hypothesized selective context for EDAR V370A was likely intertwined with selection on the fatty acid desaturase (FADS) gene cluster because it is known to modulate lipid profiles transmitted to milk from a vitamin D-rich diet high in omega-3 fatty acids.

Authors: Leslea J. Hlusko, Joshua P. Carlson, George Chaplin, Scott A. Elias, John F. Hoffecker, Michaela Huffman, Nina G. Jablonski, Tesla A. Monson, Dennis H. O’Rourke, Marin A. Pilloud and G. Richard Scott.

The synthesis presented here is a product of the American Association for the Advancement of Science’s 2017 annual meeting, as the ideas came together in the session entitled “Beringia and the Dispersal of Modern Humans to the Americas.” We thank Leslie Aiello, Marianne Brasil, Sarah Greenlee, Ophir Klein, Peter Kloess, Owen Lovejoy, Kunxin Luo, Whitney Reiner, Cat Taylor, Tim White, and three anonymous reviewers for critical feedback on earlier versions of this manuscript. Development of the ideas presented herein also benefited from conversations with Christopher Barrett, Michael Bell, Angelique Corthals, Liliana Davalos-Alvarez, Robert Dudley, Jennifer Raff, Ellen Simms, and Justin Tackney. L.J.H. also thanks the Department of Ecology and Evolution at the State University of New York at Stony Brook for feedback when she shared this research in their departmental colloquium series. Many thanks also to Christy G. Turner II, as his extensive study of incisor shoveling variation provided the foundation for the dental anthropology presented herein.


Return to top of page

May 2, 2018   Fetal Timeline   Maternal Timeline   News   News Archive

Inuit mom nursing twins, Alaska. Date: [ca. 1903-1908]
Image Credit: Lomen Brothers, Nome, Alaska

Phospholid by Wikipedia