A draft sequence of the human genome was first published in 2001. So far, 19,000 to 20,000 genes have been identified - less than expected. It is now clear that only 2% of the genome codes for proteins. This raises a question about what the other 98% of the genome is there for. At first dismissed as 'junk DNA', and thought to be an accumulation of errors during evolutionary time, it is now known to code for RNA molecules that have significant management roles within the cell.
Similar developmental processes occur in a wide variety of species, so to learn more about human development before birth, we can study other species in which the embryos are more accessible. Currently there is a focus on the role of genetic information during development, as summed up by Nüsslein-Volhard (2006): "the secret of embryonic development is the control of gene activity in time and space".
Here are some examples of model organisms that are giving us an insight into developmental processes:
slime mould Dictyostelium discoideum:
These are free-living single-celled amoebae that live in soil and feed on bacteria. When food is scarce, the cells signal to each other and stream together to form a multicellular organism called the grex. The grex migrates, and cells within it become differentiated. When a suitable location is found, the grex stops, and a fruiting body is formed, full of spores. The spores are released and drift away, becoming a new generation of free-living.
nematode worm Caenorhabditis elegans:
All 558 cells of a newly-hatched roundworm larva and 959 somatic cells of the adult are generated by strict cell lineages. There is no regulation (adaptability) of the sort seen in embryos of mammals, for example, where the loss of a particular cell in the embryo can usually be compensated for. However, widely-conserved signalling pathways are required to properly specify the cell lineages.
fruitfly Drosophila melanogaster:
The fruitfly has a short generation time – the larva hatches in 1 day, the adult fly emerges by 12 days. Morgan (1866-1945) catalogued fruitfly mutations affecting the wings, body colour, arrangement of bristles, and structure of the eyes. Multiple copies of chromosomes - 'giant' chromosomes - occur in some tissues such as the salivary glands, giving the chromosomes a banded pattern and making it possible to locate genes.
zebrafish Danio rerio:
chick embryo Gallus domesticus:
mouse Mus musculus:
The earliest steps in development after fertilisation are controlled by maternal factors. These are placed in the egg as it is being formed. For example, mRNA for the bicoid protein is anchored at the future head-end of the Drosophila egg. These maternal factors regulate the activity of zygotic genes - they are transcription factors.
Different concentrations of a maternal factor elicit different responses within nuclei. Gradients of substances within the embryo can create zones with different identity - they provide positional information. In general, the gradients of maternal factors regulate the transcription of zygotic segmentation genes - the gap genes.
The protein products of regulatory genes attach to specific control regions on the DNA. These transcription factors can either activate or repress particular genes. Mutations in maternal regulatory genes result in large regional changes (eg: lack of head or tail), while mutations in zygotic genes tend to result in more localised changes.
More complex patterns occur when the zygotic genes become active and specify their own transcription factors. Gap genes activate pair-rule genes. Pair-rule genes activate segment-polarity genes, producing the 14 main segments of the larva (and later the fly). "Control of gene activity by transcription factors is a central element in shaping life in time and space." Nüsslein-Volhard, 2006 p35
Homeotic genes are selector genes that cause different cells to adopt different states after the main regions have been established. Homeotic genes are found in all animal species examined so far and some plants. If a homeotic gene mutates, it may cause the conversion of one body part into another.
All homeotic genes contain an identical sequence of 180 nucleotides. This sequence enables the transcription factor derived from the gene to bind with DNA and switch other genes on or off. This shared sequence is called the homeobox. Genes containing this sequence are known as homeobox genes (or Hox genes in vertebrates).
Arrangement of Hox genes
Hox genes occur in clusters in the same order on the chromosomes as the order of the parts of the body they regulate during development. Thus, Hox genes affecting regions nearer the head are at one end of the cluster and genes affecting tail regions are at other end. Hox genes affecting head regions are expressed before those affecting the tail regions.
Drosophila has 8 homeotic genes, in 2 clusters. Humans have four Hox clusters - A, B, C, and D - containing a total of 39 homeotic genes.
Mutations in homeotic genes
In Drosophila, a single homeotic gene can regulate development of a whole structure. A mutation in that gene might result in an inappropriate structure being formed. In one mutation, Antennapedia, flies develop legs in place of their antennae.
It appears that Hox genes arose early during evolution and have been conserved because of their key role in embryonic development.
Hierarchy of genes
There is "a hierarchy of gene function: those genes that are active early in the process control the effects of those genes that are active later on." Nüsslein-Volhard (2006).
Nüsslein-Volhard, C. (2006) Coming to life: how genes drive development. London: Yale University Press.