Microcephalin

Key takeaways

Microcephalin belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Microcephalin to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Microcephalin from memory before moving on to harder problems.

Reference excerpt

Microcephalin (MCPH1) is a gene that is expressed during fetal brain development. Certain mutations in MCPH1, when homozygous, cause primary microcephaly—a severely diminished brain. Hence, it has been assumed that variants have a role in brain development. However, in normal individuals no effect on mental ability or behavior has yet been demonstrated in either this or another similarly studied microcephaly gene, ASPM. However, an association has been established between normal variation in brain structure, as measured with MRI (i.e., primarily cortical surface area and total brain volume) but only in females, and common genetic variants within both the MCPH1 gene and another similarly studied microcephaly gene, CDK5RAP2.

Structure Microcephalin proteins contain the following three domains:

N-terminal BRCT domain Central microcephalin protein domain (InterPro: IPR022047) C-terminal BRCT domain

Expression in the brain MCPH1 is expressed in the fetal brain, in the developing forebrain, and on the walls of the lateral ventricles. Cells of this area divide, producing neurons that migrate to eventually form the cerebral cortex.

Evolution A derived form of MCPH1 appeared about 37,000 years ago (any time between 14,000 and 60,000 years ago) and has spread to become the most common form of microcephalin throughout the world except Sub-Saharan Africa; this rapid spread suggests a selective sweep. However, scientists have not identified the evolutionary pressures that may have caused the spread of these mutations. This variant of the gene is thought to contribute to increased brain volume and may correlate with the incidence of tonal languages, though modern distributions of chromosomes bearing the ancestral forms of MCPH1 and ASPM showed neither microcephalin or ASPM had any significant effect on IQ. The derived form of MCPH1 may have originated from a lineage separated from modern humans approximately 1.1 million years ago and later introgressed into humans. This finding supports the possibility of admixture between modern humans and extinct Homo spp. While Neanderthals have been suggested as the possible source of this haplotype, the haplotype was not found in the individuals used to prepare the first draft of the Neanderthal genome.

Controversy The research results began to attract considerable controversy in the science world. John Derbyshire wrote that as a result of the findings, "our cherished national dream of a well-mixed and harmonious meritocracy [...] may be unattainable." Richard Lewontin considers the two published papers as "egregious examples of going well beyond the data to try to make a splash." Bruce Lahn maintains that the science of the studies is sound, and freely admits that a direct link between these particular genes and either cognition or intelligence has not been clearly established. Lahn is now engaging himself with other areas of study. Later studies have not found those gene variants to be associated with mental ability or cognition. Later genetic association studies by Mekel-Bobrov et al. and Evans et al. also reported that the genotype for MCPH1 was under positive selection. An analysis by Timpson et al., found "no meaningful associations with brain size and various cognitive measures". A later 2010 study by Rimol et al. demonstrated a link between brain size and structure and two microcephaly genes, MCPH1 (only in females) and CDK5RAP2 (only in males). In contrast to previous studies, which only considered small numbers of exonic single nucleotide polymorphisms (SNPs) and did not investigate sex-specific effects, this study used microarray technology to genotype a range of SNPs associated with all four MCPH genes, including upstream and downstream regulatory elements, and allowed for separate effects for males and females.

Other MCPH genes In addition to MCPH1, other genes have been designated MCPH genes based on their role in brain size. These include WDR62 (MCPH2), CDK5RAP2 (MCPH3), KNL1 (MCPH4), ASPM (MCPH5), CENPJ (MCPH6), STIL (MCPH7), CEP135 (MCPH8), CEP152 (MCPH9), ZNF335 (MCPH10), PHC1 (MCPH11) and CDK6 (MCPH12).

Research studies In March 2019, Chinese scientists reported inserting the human brain-related MCPH1 gene into laboratory rhesus monkeys, resulting in the transgenic monkeys performing better and answering faster on "short-term memory tests involving matching colors and shapes", compared to control non-transgenic monkeys, according to the researchers.

See also Bruce Lahn Genetic determinism Race and genetics Race and intelligence

References

Illustrations

Worked examples

Example 1 — a first encounter with Microcephalin

Start with the simplest possible case. Write down what Microcephalin claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Microcephalin before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Microcephalin ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Microcephalin

In research: Microcephalin appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Microcephalin in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Microcephalin is common in secondary-school and first-year university syllabi. It links to neighbouring topics Animal genes, Genes mutated in mice, Genes on human chromosome 8, so understanding it makes those chapters shorter.
In everyday life: Look for Microcephalin outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Microcephalin in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Microcephalin means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Microcephalin out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Microcephalin in simple terms?

Microcephalin (MCPH1) is a gene that is expressed during fetal brain development. Certain mutations in MCPH1, when homozygous, cause primary microcephaly—a severely diminished brain.

Why does Microcephalin matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Microcephalin?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Microcephalin.