No field of science has changed more, or changed the world more, in the last 50 years than genetics – the study of how our physical and behavioural traits are inherited.
The field’s crowning achievement may have been the spelling out of our genetic secrets by the human genome project, but scientific and technological advances in genetics have forever transformed agriculture, biology, medicine, zoology, and even fields such as anthropology and forensic science.
Why certain features of parents and even more distant relatives appear or do not appear in individual people, plants, parasites and protozoa has fascinated and confused people for millennia. This observation has also spawned a remarkable variety of theories of heredity, from pangenesis to Lamarckism. Modern genetics, however, can trace its lineage to pea plants in the garden of an Augustinian monk, Gregor Mendel. By studying the inheritance of traits such as plant height and wrinkly peas, he discovered that most hereditary traits are carried by discrete factors, later called genes.
Dominant and recessive
These experiments illuminated many of the key principles of genetics. For example, they revealed that most organisms have two copies of each gene, one from each parent, and that a gene comes in a variety of different forms, or alleles.
A purebred tall pea plant has two tall alleles of a gene for height (often abbreviated as TT), and the short plants have two short alleles (tt). Their offspring have one of each (Tt). This first generation is tall because the tall allele is dominant.
Recessive traits, such as shortness in pea plants, are only expressed when two recessive alleles meet up. This is also a good example of how organisms of the same appearance, or phenotype (the tall parent and their offspring), can have different genotypes, or combinations of genes (TT versus Tt).
It was nearly 100 years after Mendel published his work that scientists discovered genes are composed of the double-helical molecule DNA, which is built from four chemical letters, or bases: adenine, thymine, cytosine and guanine. The discovery of the structure of DNA in 1953 immediately suggested a simple mechanism for DNA replication: the two strands of the helix could unzip and allow enzymes to enter and synthesise two new strands.
The goal of the human genome project was to use DNA sequencing to reveal all three billion DNA letters in our chromosomes and find all our genes. By comparing our genetic make-up to the genomes of mice, chimps and a menagerie of other species (rats, chickens, dogs, pufferfish, the microscopic worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and many bacteria), scientists have learned a great deal about how genes evolve over time, and gained insights into human diseases.
Another powerful technology leading the genetics revolution is the polymerase chain reaction (PCR), which allows large quantities of DNA sequence information to be derived from tiny and highly damaged samples.
PCR has become the linchpin in many criminal investigations, now that traces of blood, semen or skin left at a crime scene (even decades previously) can condemn a criminal or exonerate innocent suspects. This technology is also reshaping notions of both human ancestry and the evolutionary history of many species, by harvesting genes from ancient remains, including fossil DNA. Other new techniques could prove even faster than PCR.
Life’s instruction manual
Here’s how genes work. When a gene is switched on, one of its strands is copied into the related chemical RNA, a process known as transcription. For most known genes this “messenger” or mRNA is then shuttled off to a ribosome of a cell where its translation into a protein sequence occurs. Ribosomes decipher the sequence of an mRNA with the help of small cloverleaf shaped molecules called “transfer” or tRNA.
In inherited diseases, some part of this process has gone awry due to a mutation, or change in the DNA sequence. Cystic fibrosis, achondroplasia, phenylketonuria and Huntington’s disease are each caused by simple changes in the sequence of a single gene.
Other diseases with a more complex genetic component include diabetes and epilepsy. Down’s syndrome, haemophilia, fragile X syndrome, sickle-cell anaemia, thalassaemia and a plethora of other disorders are also down to genetic defects.
In our cells, many hundreds of genes are joined end-to-end on DNA strands and tightly packed into sausage-shaped structures called chromosomes which are stored in a cell’s nucleus. A locus is the position of a gene on a chromosome. Chromosomes also possess physical features which protect their genetic cargo. Telomeres at their ends act as caps to prevent biochemical wear and tear, while the cell choreographs the movement of chromosomes by grabbing hold of its centromere handle.
The dance of chromosomes is tightly controlled during cell replication to preserve the genetic makeup of cells. During normal growth, cells replicate through mitosis and each “daughter” inherits the same number of chromosomes and genes as its parent. But sperm and eggs contain half the number of chromosomes because they form through a different process called meiosis. Then when sperm and egg fuse to make a zygote, it contains the same number of genes and chromosomes as its parents.
Sex and linkage
Many human genes are inherited exactly as Mendel envisaged, with one copy from each parent. Human blood type falls into this category of Mendelian inheritance. But heredity can also be more complicated. DNA sequences that lie near each other on chromosomes exhibit gene linkage and are usually inherited together, even though they may be unrelated in function. Another exception are so-called sex-linked traits, encoded on the sex chromosomes.
Men inherit one X and one Y chromosome (which encodes the gene for maleness), so they are more likely to express recessive traits from the X, such as colour blindness and haemophilia. Women are more protected, because they have two X chromosomes. Finally, the mitochondria – the energy powerhouse of the cell – contains its own small parcel of mitochondrial DNA which is inherited exclusively from the egg, and therefore the mother.
The genetic variation of individual DNA sequences in a population is called its genetic diversity. Diversity results from the re-assortment of genes during meiosis and genetic mutation. Genetic variation drives evolution by creating a range of phenotypes that might give individuals a competitive edge in different environments.
Those individuals with the fittest combination of alleles produce more offspring. Inbreeding can be dangerous for a population because it removes variation and the ability to adapt to new environments. While natural selection favours the accumulation of fit alleles of beneficial genes, the majority of chromosomes in many organisms are composed of “selfish DNA“, which does not benefit its host and seems to play no other role other than ensuring its own replication.
The most powerful aspect of the new genetics is genetic engineering – the ability to design new genetic sequences and insert them into viruses, bacteria, flies, plants, mice and other animals. This has been a boon for research, and led to the birth of biotechnology and many practical applications.
Doctors have been experimenting with gene therapy to supply healthy copies of a gene to patients suffering from a genetic defect. Genetically engineered vaccines incorporate genetic pieces of a deadly microbe to stimulate the immune system, without the danger of infection. And companies are using genetic modification to create hardier plants and animals that resist disease, grow faster or produce healthier food.