Tag: gene

  • The Gene Switches That Set Humans Apart From Monkeys

    The Gene Switches That Set Humans Apart From Monkeys

    Researchers have pinpointed areas of the human genome that may be accountable for our unique human abilities. The DNA regions, known as HAQERs (Human Ancestor Quickly Evolved Regions), regulate the expression of protein-coding genes and play a role in the formation of our brain, digestive system, and immune system. They arose soon after the split between human and chimpanzee ancestry. Despite their usefulness, HAQERS can spread illness.

    While chimpanzees and gorillas are primates like us, there are important ways in which we humans stand apart from them. Even though there are few variations between human and great ape protein-coding genes, progress has been slow in elucidating the genetic basis of our “essentially human” traits. However, there is mounting evidence that the most significant alterations occurred in regions of our genome that do not code for proteins and were previously thought to be meaningless “junk DNA.”

    Quick Shifts

    An American research group led by Riley Mangan of Duke University has started looking for evidence of human evolution in these non-coding regions of the genome. Up until recently, it was thought that the most promising DNA sequences were those that were relatively stable for a long period of time yet underwent significant alteration in our ancestors. It was thought that a shift in selection was responsible for the rapid pace of molecular evolution.

    On the other hand, Mangan and his team have searched previously volatile parts of the genome. Unlike in other animals, humans’ brain sizes, limb lengths, and face proportions varied throughout time. The scientists used high-throughput sequencing and genome comparisons to hunt for DNA segments in these genomic locations that altered very fast after the chimpanzee and human lineages separated around 7.5 million years ago.

    Inherent HAQER in Our DNA

    Indeed, the team was able to single out almost 1,500 such passages. The acronym HAQER, which stands for “Human Ancestor Quickly Evolved Regions,” was given to these places. According to the findings, these regions of DNA have undergone some of the most rapid changes throughout the human genome. However, when exactly did this dramatic evolutionary leap occur on the timeline of early, or prehistoric, human development? Or did it occur before the divergence from chimpanzees?

    After human ancestry diverged from that of the chimpanzee, we subsequently developed the HAQER regions.

    This was confirmed by comparing the 13 most relevant sequences from Mangan’s HAQERs sections to those of Neanderthals, Denisova people, chimpanzees, and the reconstructed genome of the presumed common ancestor of humans and chimps.

    This means that the HAQERs originated after our ancestors diverged from those of the chimpanzee but before those of the Denisova people and Neanderthals. This means that these sequences were present in other early human and prehuman animals.

    Regulating the Nervous System and Digestive System

    So, why do we need the HAQER sequences? The researchers refer to these snippets of DNA as “regulatory DNA” because of their “switch-like” function. Specifically activating genes seems to be a result of this process. There are certain cell types where this occurs, as well as specific stages of development when this occurs. And sometimes it takes a shift in circumstances, as Mangan’s coworker Craig Lowe describes. There were certain gene switches in the human operating system that the HAQERs introduced.

    Research has shown that these gene switches play an important role in shaping the human nervous system, digestive system, and immune system. The gene switches empower us to fine-tune our responses to shifting environmental conditions.

    Typical Human Illnesses May Be Triggered by HAQERs

    What caused HAQERs to emerge? Rapid appearance of genomic areas often has one of two causes: either they are the result of local mutations or they are so beneficial to a species that they become established via natural selection. The scientists discovered support for both hypotheses in the newly described DNA sequences, indicating that the most diverse sections of the human genome were sculpted by a combination of these two processes.

    The researchers speculate that HAQERs, in making us humans, not only provided us with favorable qualities like huge brains, but also formed the foundation for common human disorders. Conditions including schizophrenia, bipolar disorder, and unipolar depression may fall within this category.

    Mangan and his coworkers found that, although all people have very identical HAQER sequences, there are still some differences, and that these variations have a tendency to correspond with certain diseases. More study may be needed to determine the nature of the connection.

  • How pioneer factors dissolve the compressed genetic material

    How pioneer factors dissolve the compressed genetic material

    A fertilized egg cell must decompress its genes before it can develop into an embryo. Scientists have finally figured out how it accomplishes this feat. According to the findings, a so-called “pioneer factor” is responsible for opening the chromatin packing of the genetic material during fertilization, allowing the genes crucial for early cell division to be read.

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    This is the only way the embryo can develop beyond the two-cell stage.

    If everything goes well, a new life starts when a sperm fertilizes an egg. Things may go wrong even when the mother’s and father’s chromosomes fuse together. However, the following phases are not without their own challenges: The newly fused DNA in a fertilized egg cell has to be “awakened” before it can divide. So-called pioneer factors are responsible for reading the relevant parts of DNA during cell division.

    The future embryo undergoes its first round of cell divisions shortly after fertilization. On the other hand, this requires the reading of at least some genes.

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    Obtaining the genetic material from its sealed packaging

    In a fertilized egg cell, the pioneer factor Nr5a2 (red) interacts to the inactive DNA (gray) that is still wrapped around histones. Thereby, it wakes the genome. Essential genes for embryonic development may now be obtained.
    In a fertilized egg cell, the pioneer factor Nr5a2 (red) interacts to the inactive DNA (gray) that is still wrapped around histones. Thereby, it wakes the genome. Essential genes for embryonic development may now be obtained. (Credit: Max Iglesias)

    Molecules in the cytoplasm of the egg cells that are passed down from the mother are useful even during the first cell division. When an embryo reaches the two-cell stage, however, the cells are on their own. The thing is, the genetic code is not openly available in the nucleus of the cell. DNA is present as a long strand that is wrapped like a string of pearls around smaller packing proteins called histones, as explained by co-author and Max Planck Institute researcher Siwat Ruangroengkulrith.

    The embryonic cells need to decode the first genes from this packing at certain locations before they can make the transcription factors required for further cell divisions. But the DNA thread is shortened by as much as 40,000-fold when twisted into histones.

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    It was previously unclear which unpacker molecules, in the form of so-called pioneer factors, liberate the compressed genetic information and allow for successive cell divisions.

    The first genes in a fertilized cell are read by a specific pioneer factor.

    The key molecule

    First author Johanna Gassler of the MPI of Biochemistry and her colleagues have shed light on this issue. First, scientists determined in mice which transcription factors are active throughout the development of an embryo and which genes were available for reading. Researchers sought for sequence features shared by the earliest-stage mRNA molecules they isolated and found many.

    A closer look at the molecules involved has highlighted the crucial function played by one in particular: Nr5a2, the pioneering factor. Embryonic development cannot go through the two-cell stage without it, since it is essential for activating the genome at that time. This pioneering factor seems to be transmitted from the maternal egg cell to the developing embryo.

    The absence of Nr5a2

    Without Nr5a2, no additional embryonic processes may begin. Through their tests, they demonstrated that inhibiting Nr5a2 prevents the production of the vast majority of mRNA molecules in early embryos. Embryos are also prevented from developing further. This indicates the significance of Nr5a2 in the first stages of embryonic development.

    The team was also successful in elucidating the mechanism behind this pioneering factor. Experiments have demonstrated that Nr5a2 may unlock dormant DNA sequences, allowing other genes’ transcription machinery to reach those regions. To begin the process of unpacking and reading the genetic information in embryos, the molecule docks onto the chromatin envelope of the DNA.

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    Additional transcription factors are then released, which control further reading.

    Relevant understanding of the first moments of existence

    Important progress has been made toward a mechanistic understanding of the origin of life with the revelation that Nr5a2 plays a vital role in genome awakening. Researchers believe there must be more components at play, but they haven’t been able to pin them down yet.