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Welcome to The Visible Embryo, a comprehensive educational resource on human development from conception to birth.

The Visible Embryo provides visual references for changes in fetal development throughout pregnancy and can be navigated via fetal development or maternal changes.

The National Institutes of Child Health and Human Development awarded Phase I and Phase II Small Business Innovative Research Grants to develop The Visible Embryo. Initally designed to evaluate the internet as a teaching tool for first year medical students, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than one million visitors each month.

Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive Jan 15, 2014


Last year, researchers reported shuffling some genes in mice to create Y-less males that could
produce normal offspring, leading some commentators to wonder whether the Y chromosome
is superfluous. Today's research finds the Y chromosome's puny size – it contains
27 unique genes versus thousands on other chromosomes –
is a sign that it is lean and stripped down to essential genes.

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Stripped-down Y chromosome key to fertility

A comparison of Y chromosomes in eight African and eight European men dispels the common notion that Y genes are mostly unimportant or may even be destined to continue to dwindle and eventually disappear.

"The Y chromosome has lost 90 percent of the genes it once shared with the X chromosome, and some scientists have speculated that the Y chromosome will disappear in less than 5 million years," adds evolutionary biologist Melissa A. Wilson Sayres, a Miller Postdoctoral Fellow in the Department of Integrative Biology at the University of California, Berkeley, and lead author of the new analysis.

Some mammals have already lost their Y chromosome, though they still have males and females and reproduce normally. Last month, researchers reported shuffling some genes in mice to create Y-less males that could produce normal offspring. This lead some commentators to wonder whether the Y chromosome is superfluous.

"Our study demonstrates that the Y genes that have been maintained, and those that migrated from the X to the Y, are important. The Y is going to be around for a long while."

Melissa A. Wilson-Sayres, an evolutionary biologist , and Miller Postdoctoral Fellow in the Department of Integrative Biology, University of California, Berkeley

Wilson-Sayres and coauthor Rasmus Nielsen, UC Berkeley professor of integrative biology, report in PLOS Genetics that patterns of variation on the Y chromosome, among 16 men, are consistent with natural selection. They maintain that much of the content of the Y gene plays a role in male fertility. Although puny – 27 unique genes versus thousands on other chromosomes – its size is simply a sign the Y is lean and stripped down to essentials.

"Wilson-Sayres's results are quite stunning. They show that because there is so much natural selection working on the Y chromosome, there has to be a lot more function on the chromosome than people previously thought," Nielsen said.

Variations in Y chromosomes are used to track how human populations moved around the globe, and according to Nielsen, the new research will help improve estimates of human evolutionary history.

"Melissa has shown that this strong negative selection – natural selection to remove deleterious genes – tends to make us think the dates are older than they actually are, which gives quite different estimates of our ancestors' history," Nielsen said.

Y has degraded over the past 200 million years

Before about 200 million years ago, when mammals were relatively new on Earth, early versions of both sex chromosomes, X and Y, were just like any other pair of chromosomes. With each generation, X and Y swap a few genes so that offspring are a mix of their parents' genes. Fertilized eggs that got two proto-X genes became female and eggs with one proto-X and one proto-Y became male.

But according to Dr. Wilson-Sayres, for some reason the gene that triggers a cascade of events resulting in male features became fixed on the Y chromosome. That attracted other male-specific genes, such as those that control development of the testes, sperm and semen. Many of these genes turned out to be harmful to females, so the X and Y stopped swapping genes and the two chromosomes began to evolve separately.

"Now that the X and Y do not swap DNA over most of their length, the Y cannot efficiently fix mistakes and has degraded over time," she adds. "In XX females, the X still has a partner to swap with and fix gene mistakes, which is why we think of the X as not degraded."

Wilson-Sayres was fascinated by the strange history of the sex chromosomes and in particular the lack of genetic variation worldwide on the Y chromosome. Gene variation markers seen in DNA on non-sex chromosomes, are used to chart human population migration through history — but are poorly characterized across the entire Y chromosome.

"Y chromosomes are more similar to each other than we expected," said Wilson-Sayres. "There has been some debate about whether this is because there are fewer males contributing to the next generation, or whether natural selection is acting to remove variation."

Did fewer males contribute genes to Y chromosome?

UC Berkeley researchers demonstrated that if fewer males were the true cause of Y's low variability, it would suggest fewer than 1 in 4 males throughout history, had passed on their Y chromosome to each generation.

Variations in other human chromosomes, including the X chromosome, make this an unlikely scenario.

Instead, research shows that low Y variation can be explained by intense natural selection — a strong evolutionary pressure to weed out bad mutations which ended up trimming the Y chromosome to its essentials.

Wilson-Sayres: "We show a model of purifying selection acted on the Y chromosome, removing harmful mutations. That process, combined with a moderate reduction in the number of males passing on their Y chromosomes, can explain low Y diversity."

Researchers also found that all 27 genes on the Y chromosome –17 retained after 200 million years and 10 genes recently acquired (though poorly understood) – are likely the result of natural selection. Most of the newer genes, called ampliconic genes*, are present in multiple copies on the chromosome. Loss of one or more of these copies has been linked to male infertility.

*[From Wikipedia, the free encyclopedia: An amplicon is a piece of DNA or RNA that is the source and/or product of natural or artificial amplification or replication events. It can be formed using various methods including polymerase chain reactions (PCR), ligase chain reactions (LCR), or natural gene duplication. In this context, "amplification" refers to the production of one or more copies of a genetic fragment or target sequence, specifically the amplicon. As the product of an amplification reaction, amplicon is used interchangeably with common laboratory terms, such as PCR product.]

"These ampliconic regions that we haven't really understood until now are evidently very important and probably should be investigated and studied for issues of infertility," said Wilson-Sayres.

Wilson-Sayres was able to precisely measure Y variability by, for the first time, comparing Y's variation with variations found in that same person's other 22 chromosomes (autosomes), their X chromosome, and with their mitochondrial DNA. She compared whole genome data from 16 men whose DNA had been sequenced by the Mountain View-based company Complete Genomics Inc.

Complete Genomics Inc. was recently acquired by BGI, the Bejing Genome Institute.

Cross-population studies of variation in the Y chromosome are in their infancy, Dr. Sayres added, noting that of the more than 36 mammalian genomes sequenced to date, complete Y chromosomes are only available for three.

Most of the 1,000+ human genomes already sequenced do not have sufficient accurate coverage of the Y to make this type of comparison among individuals, but advances in technology to better characterize DNA will facilitate future analyses of the Y chromosome, Sayres concluded.

The human Y chromosome exhibits surprisingly low levels of genetic diversity. This could result from neutral processes if the effective population size of males is reduced relative to females due to a higher variance in the number of offspring from males than from females. Alternatively, selection acting on new mutations, and affecting linked neutral sites, could reduce variability on the Y chromosome. Here, using genome-wide analyses of X, Y, autosomal and mitochondrial DNA, in combination with extensive population genetic simulations, we show that low observed Y chromosome variability is not consistent with a purely neutral model. Instead, we show that models of purifying selection are consistent with observed Y diversity. Further, the number of sites estimated to be under purifying selection greatly exceeds the number of Y-linked coding sites, suggesting the importance of the highly repetitive ampliconic regions. While we show that purifying selection removing deleterious mutations can explain the low diversity on the Y chromosome, we cannot exclude the possibility that positive selection acting on beneficial mutations could have also reduced diversity in linked neutral regions, and may have contributed to lowering human Y chromosome diversity. Because the functional significance of the ampliconic regions is poorly understood, our findings should motivate future research in this area.

Author Summary
The human Y chromosome is found only in males, and exhibits surprisingly low levels of genetic diversity. This low diversity could result from neutral processes, for example, if there are fewer males successfully mating (and thus fewer Y chromosomes being inherited) relative to the number of females who successfully mate. Alternatively, natural selection may act on mutations on the Y chromosome to reduce genetic diversity. Because there is no recombination across most of the Y chromosome all sites on the Y are effectively linked together. Thus, selection acting on any one site will affect all sites on the Y indirectly. Here, studying the X, Y, autosomal and mitochondrial DNA, in combination with population genetic simulations, we show that low observed Y chromosome variability is consistent with models of purifying selection removing deleterious mutations and linked variation, although positive selection may also be acting. We further infer that the number of sites affected by selection likely includes some proportion of the highly repetitive ampliconic regions on the Y. Because the functional significance of the ampliconic regions is poorly understood, our findings should motivate future research in this area.

The work was funded by UC Berkeley's Miller Institute. Kirk Lohmueller of UCLA is a coauthor of the paper.