A new gene linked to autism may be the first completely new gene distinguishing humans from Neanderthal and ancient hominid cousins:
Xander Nuttle et al. Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility, Nature (2016). DOI: 10.1038/nature19075This finding supports other research suggesting that autism is correlated with increased micro-deletions and duplications. But it also extends that research by showing how genetic flexibility has liabilities and those liabilities may shift in relation to environmental inputs that increase pressures for re-organization.
Background: The Subtle Dance of Genomic Instability
Genomic integrity is a subtle dance of reproduction that must maintain enough structural integrity to prevent cascading failures but also flexible enough to allow evolutionary adaptation to changing environmental conditions. It appears that certain chromosomes have zones that are more susceptible to re-organization in response to environmental inputs than others. Re-organization in these susceptible zones can confer advantages but also result in cascading errors.
Evolutionary studies of the human genome have revealed that gene duplications in humans in particular genetic zones conferred evolutionary advantages and also potential disadvantages. The gene duplications occur in areas of the genome that are particularly prone to re-organization. Here is background research on the role of segmental duplication in chromosome 16 in human evolution:
Eichler et al. 2008. A burst of segmental duplications in the genome of the African great ape ancestor. Nature 457, 877-881 (12 February 2009) | doi:10.1038/nature07744; Received 29 August 2008; Accepted 18 December 2008 http://www.nature.com/nature/journal/v457/n7231/full/nature07744.html
Did increased gene duplication set the stage for human evolution? Phy.Org, February 11, 2009 http://phys.org/news/2009-02-gene-duplication-stage-human-evolution.html#jCp
Eichler's research team found an especially high rate of duplications in the ancestral species leading to chimps and humans, even though other mutational processes, such as changes in single DNA letters, were slowing down during this period. "There's a big burst of activity that happens where genomes are suddenly rearranged and changed," he says.
Surprisingly, the rate of duplications slowed down again after the lineages leading to humans and to chimpanzees diverged. "You might like to think that humans are special because we have more duplications than did earlier species," he says, "but that's not the case."Too much disorganization in that process – such as recurrent deletions and duplications – are associated with autism and schizophrenia among other disorders, as established in the new study cited at the beginning of this post (Xander Nuttle et al. Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility, Nature (2016). DOI: 10.1038/nature19075 ).
These duplications have created regions of our genomes that are especially prone to large-scale reorganizations. "That architecture predisposes to recurrent deletions and duplications that are associated with autism and schizophrenia and with a whole host of other diseases," says Eichler.
Yet these regions also exhibit signs of being under positive selection, meaning that some of the rearrangements must have conferred advantages on the individuals who inherited them. Eichler thinks that uncharacterized genes or regulatory signals in the duplicated regions must have created some sort of reproductive edge. "I believe that the negative selection of these duplications is being outweighed by the selective advantage of having these newly minted genes, but that's still unproven," he said.
From an evolutionary perspective, this capacity for re-organization conferred reproductive advantages over the costs.
Environmental Inputs, Re-Organization and Genomic Instabilities
However, what if forces of re-organization overwhelm genomic fidelity to the point that accelerated error produces risks that begin to outweigh benefits?
Perhaps genomic instabilities result from too much re-organization/dis-organization catalyzed by environmental inputs?
Here is an accessible and fascinating article that I recommend reading describing findings by Xander Nuttle (2016) on the role of chromosomal re-organization on human evolution and neurological disorders such as autism and schizophrenia.
Basically, the research is proposing that are an area on chromosome 16 in the human genome contains copy-number variants that are not found in other hominids. This distinction conferred genetic benefits because it spread quickly from an evolutionary perspective but it also produced some costs, including genetic disorders such as autism:
Michael Mccarthy. August 4, 2016 Human-Neanderthal gene variance is involved in autism. Medical Express.http://medicalxpress.com/news/2016-08-human-neanderthal-gene-variance-involved-inautism.htmlI believe that autism is an encompassing term for a variety of biological and psychological symptoms so I doubt this finding alone explains all cases of the disorder.
The structure involves a segment of DNA on chromosome 16 that contains 28 genes. This segment is flanked by blocks of DNA whose sequences repeat over and over.
Such stretches of duplicated DNA, called copy-number variants, are common in the human genome and often contain multiple copies of genes. Although most copy-number variants seem to have no adverse effect on health, some have been linked to disease.
However, when both strands of a segment of DNA are flanked by highly identical sequences, they can be susceptible to large copy-number differences, including deletion, duplication and other changes, during the process of cell division. In this case, deletion, which causes the loss of the segment's 28 genes, results in autism.
DeNovo mutations and genomic instabilities have previously been linked to autism. Findings on autism susceptibility alleles and mutations point most consistently to areas on chromosomes 7q, 15q, 16p and 17q (Autism Genome Project Consortium et al. 2007; Landrigan, Lambertini, & Birnbaum, 2012; Sakurai et al, 2011).
Radiation exposure may also play a role in autism because mitochondrial DNA is particularly susceptible to mutation from background radiation. Radiation exposure increases the frequency of DNA strand breaks in mitochondria (Lutz-Bonengel, Brinkmann, Forster, Forster, & Willkomm, 2002).
That said, the 2016 Xander Nuttle study does identify how a genetic advantage under evolutionary pressures may become a genetic disadvantage in the highly mutagenic environment we have wrought with human-engineered radiation, toxic isotopes, and disruptive chemicals.
Chromosome 16, Re-Organization and Ionizing Radiation
Chromosome 16, the one that contains that zone subject to re-organization, is highly radiosensitive in comparison to other human chromosomes:
Camparoto M.L., Takahashi-Hyodo S.A., Dauwerse J.G. Natarajan A.T. · Sakamoto-Hojo. 2005. High Susceptibility of Chromosome 16 to radiation-induced chromosome rearrangements in human lymphocytes under in vivo and in vitro exposure. Cytogenet Genome Res 108:287–292 (2005) (DOI:10.1159/000081522).
Our results indicate that chromosome 16 is more prone to radiation-induced chromosome breaks, and demonstrate a non-random distribution of induced aberrations. This information is valuable for retrospective biological dosimetry in case of human exposure to radiation, since the estimates of absorbed doses are calculated by determining the translocation frequency for a sub-set of chromosomes, and the results are extrapolated to the whole genome, assuming a random distribution of induced aberrations.Chromosome 16 is susceptible to re-organization because it is susceptible to ionizing radiation and perhaps to other genotoxins. It is easy to postulate that human evolutionary changes can be traced in part to bursts of gamma radiation from the sun or space. But permanence and change must be carefully navigated because too much disorder, or perhaps particular forms of order, result in cascading errors that impact neurology, resulting in disorders such as autism and multiple sclerosis.
Environmental accounts of autism rarely address ionizing radiation. They tend to focus on chemicals and toxic elements such as arsenic and mercury. Environmental chemists and epidemiologists don’t usually study autism and ionizing radiation.
Research findings on chromosome 16 and susceptibility to ionizing radiation suggest more research is needed on the linkage between ionizing radiation and autism and other neurological disorders.
It is possible that the environment we have wrought produces more re-organization than our collective human genome can withstand without suffering cascading errors.