Microcephalin
Encyclopedia
Microcephalin is one of six gene
s causing primary microcephaly
when non-functional mutation
s exist in the homozygous state. Derived from the Greek
words for "small" and "head", this condition is characterised by a severely diminished brain
.
Hence it has been assumed that variants have a role in brain development, but in normal individuals no effect on mental
ability, brain size or behavior
has been attributed to either this or another similarly studied microcephaly gene, ASPM.
brain, in the developing forebrain, and on the walls of the lateral ventricles
. Cells
of this area divide, producing neuron
s that migrate to eventually form the cerebral cortex
.
D 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 throughout the world except Sub-Saharan Africa
; this rapid spread suggests a selective sweep
. However, scientists have not identified the evolutionary pressure
s that may have caused the spread of these mutations. Modern distributions of chromosome
s bearing the ancestral forms of MCPH1 and ASPM are correlated with the incidence of tonal languages, but the nature of this relationship is far from clear.
Haplogroup D 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 Neanderthal
s 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.
, writing in The National Review Online, 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." Lahn maintains that the science of the studies are sound, and freely admits that a direct link between these particular genes and either cognition or intelligence has not been clearly established. Bruce Lahn is now engaging himself with other areas of study.
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., however, found "no meaningful associations with brain size and various cognitive measures".
The microcephaly-related loci MCPH 3, 5 and 6 are usually classified by their alternate names CDK5RAP2
, ASPM and CENPJ
respectively, according to their other roles. (More information can be found from the articles dedicated to them and links in the information boxes.)
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s causing primary microcephaly
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
when non-functional mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s exist in the homozygous state. Derived from the Greek
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
words for "small" and "head", this condition is characterised by a severely diminished brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
.
Hence it has been assumed that variants have a role in brain development, but in normal individuals no effect on mental
Mind
The concept of mind is understood in many different ways by many different traditions, ranging from panpsychism and animism to traditional and organized religious views, as well as secular and materialist philosophies. Most agree that minds are constituted by conscious experience and intelligent...
ability, brain size or behavior
Behavior
Behavior or behaviour refers to the actions and mannerisms made by organisms, systems, or artificial entities in conjunction with its environment, which includes the other systems or organisms around as well as the physical environment...
has been attributed to either this or another similarly studied microcephaly gene, ASPM.
Structure
Microcephalin proteins contain the following three domains:- N-terminal BRCT domainBRCT domainBRCA1 C Terminus domain is a family of evolutionarily related proteins.The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage, for example as found in the breast cancer DNA-repair protein BRCA1...
- Central microcephalin protein domain
- C-terminal BRCT domain
Expression in the brain
MCPH1 is expressed in the fetalFetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
brain, in the developing forebrain, and on the walls of the lateral ventricles
Lateral ventricles
The lateral ventricles are part of the ventricular system of the brain. Classified as part of the telencephalon, they are the largest of the ventricles....
. Cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
of this area divide, producing neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s that migrate to eventually form the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
.
Evolution
A derived form of MCPH1 called haplogroupHaplogroup
In the study of molecular evolution, a haplogroup is a group of similar haplotypes that share a common ancestor having the same single nucleotide polymorphism mutation in both haplotypes. Because a haplogroup consists of similar haplotypes, this is what makes it possible to predict a haplogroup...
D 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 throughout the world except Sub-Saharan Africa
Sub-Saharan Africa
Sub-Saharan Africa as a geographical term refers to the area of the African continent which lies south of the Sahara. A political definition of Sub-Saharan Africa, instead, covers all African countries which are fully or partially located south of the Sahara...
; this rapid spread suggests a selective sweep
Selective sweep
A selective sweep is the reduction or elimination of variation among the nucleotides in neighboring DNA of a mutation as the result of recent and strong positive natural selection....
. However, scientists have not identified the evolutionary pressure
Evolutionary pressure
Any cause that reduces reproductive success in a proportion of a population, potentially exerts evolutionary pressure or selection pressure. With sufficient pressure, inherited traits that mitigate its effects - even if they would be deleterious in other circumstances - can become widely spread...
s that may have caused the spread of these mutations. Modern distributions of chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s bearing the ancestral forms of MCPH1 and ASPM are correlated with the incidence of tonal languages, but the nature of this relationship is far from clear.
Haplogroup D 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
Archaic Homo sapiens
Archaic Homo sapiens is a loosely defined term used to describe a number of varieties of Homo, as opposed to anatomically modern humans , in the period beginning 500,000 years ago....
spp. While Neanderthal
Neanderthal
The Neanderthal is an extinct member of the Homo genus known from Pleistocene specimens found in Europe and parts of western and central Asia...
s 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 DerbyshireJohn Derbyshire
John Derbyshire is a British-American writer. His columns in National Review and cover a broad range of political-cultural topics, including immigration, China, history, mathematics, and race. Derbyshire's 1996 novel, Seeing Calvin Coolidge in a Dream, was a New York Times "Notable Book of the...
, writing in The National Review Online, wrote that as a result of the findings, "our cherished national dream of a well-mixed and harmonious meritocracy [...] may be unattainable." Richard Lewontin
Richard Lewontin
Richard Charles "Dick" Lewontin is an American evolutionary biologist, geneticist and social commentator. A leader in developing the mathematical basis of population genetics and evolutionary theory, he pioneered the notion of using techniques from molecular biology such as gel electrophoresis to...
considers the two published papers as "egregious examples of going well beyond the data to try to make a splash." Lahn maintains that the science of the studies are sound, and freely admits that a direct link between these particular genes and either cognition or intelligence has not been clearly established. Bruce Lahn is now engaging himself with other areas of study.
Later genetic association studies
Genome-wide association study
In genetic epidemiology, a genome-wide association study , also known as whole genome association study , is an examination of many common genetic variants in different individuals to see if any variant is associated with a trait...
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., however, found "no meaningful associations with brain size and various cognitive measures".
Family members
In addition to MCPH1. the other five family members are:The microcephaly-related loci MCPH 3, 5 and 6 are usually classified by their alternate names CDK5RAP2
CDK5RAP2
CDK5 regulatory subunit-associated protein 2 is a protein that in humans is encoded by the CDK5RAP2 gene.-Interactions:CDK5RAP2 has been shown to interact with CDK5R1.-Further reading:...
, ASPM and CENPJ
CENPJ
Centromere protein J is a protein that in humans is encoded by the CENPJ gene. It is also known as centrosomal P4.1-associated protein .-Further reading:...
respectively, according to their other roles. (More information can be found from the articles dedicated to them and links in the information boxes.)
See also
- Genetic determinismGenetic determinismGenetic determinism is the belief that genes determine morphological and behavioral traits and do so with little or no influence from environmental factors....
- Race and genetics
- Race and intelligence
- Bruce LahnBruce LahnBruce Lahn is a geneticist at the University of Chicago. He is also the founder of the Center for Stem Cell Biology and Tissue Engineering at Sun Yat-sen University, Guangzhou, China. His previous research specialized in human genetics and evolutionary genetics, especially human sex chromosome...
External links
- Neanderthal Brains - a lecture by Bruce Lahn - from the NYASNew York Academy of SciencesThe New York Academy of Sciences is the third oldest scientific society in the United States. An independent, non-profit organization with more than members in 140 countries, the Academy’s mission is to advance understanding of science and technology...
podcasts. - GeneReviews/NCBI/NIH/UW entry on Primary Autosomal Recessive Microcephaly
- Medterms
- JBC
- OUP Journals
- EMBL