10 min readConcept sheet1-mark MCQ on salient features, a 2-mark question on goals or methods (ESTs, sequence annotation), and a 3-mark question on the findings; also a NEET favourite

The Human Genome Project and the rice genome

The Human Genome Project (1990 to 2003) read the 3 billion base pairs of human DNA. It found under 2% codes for proteins. Rice was sequenced later.

Human Genome Project (HGP)13 years, 1990 to 2003; coordinated by the US Department of Energy and the National Institute of Health, with the Wellcome Trust (UK) and others

Human genome3164.7 million nucleotide bases; about 30,000 genes (estimate)

Two approachesExpressed Sequence Tags (ESTs): find genes expressed as RNA. Sequence annotation: sequence everything, then assign functions

Rice genome (extra reading, not in your textbook)Oryza sativa: 12 chromosomes (2n = 24), about 389 million bp, sequenced by an international project in which India took part

Goals of the Human Genome Project

Identify all the roughly 20,000 to 25,000 genes in human DNA.
Find the sequence of the 3 billion chemical base pairs in human DNA.
Store this information in databases.
Improve tools for data analysis.
Transfer the related technologies to other sectors, such as industry.
Address the ethical, legal and social issues (ELSI) that the project may raise.

ESTs vs sequence annotation

Expressed Sequence Tags (ESTs)Focus on genes that are expressed as RNA. Only the parts of the genome that are actually used are identified.

Sequence annotationSequence the whole genome, coding and non-coding, and later assign functions to its different regions.

How the genome was sequenced

The data is huge: printed at 1000 letters a page and 1000 pages a book, the sequence of one haploid set would fill about 3300 books. So high-speed computers and **bioinformatics** were essential.

1
Isolate the total DNA and break it into random fragments of small size.
2
Clone the fragments in a host (bacteria or yeast) using special vectors: BAC (bacterial artificial chromosomes) and YAC (yeast artificial chromosomes). This makes many copies of each piece.
3
Sequence the fragments with automated DNA sequencers based on Frederick Sanger's method.
4★
Arrange the sequences using their overlapping regions, with special computer programs.
5
Annotate the sequence and assign it to chromosomes. Genetic and physical maps were made using restriction site polymorphism and repetitive DNA (microsatellites).
6
The last chromosome to be completed was chromosome 1, in May 2006.

★ key step

Salient features of the human genome

It has 3164.7 million nucleotide bases.
An average gene has 3000 bases, but sizes vary; the largest known gene, dystrophin, has 2.4 million bases.
Total genes are estimated at about 30,000, far fewer than earlier guesses of 80,000 to 1,40,000.
99.9% of the bases are exactly the same in all people.
The functions of over half of the discovered genes are unknown.
Less than 2% of the genome codes for proteins.
Repeated sequences make up a very large part of the genome. They have no direct coding role but tell us about chromosome structure and evolution.
Chromosome 1 has the most genes (2968) and the Y chromosome the fewest (231).
About 1.4 million places have single-base differences between people: SNPs (single nucleotide polymorphisms, said 'snips').

Extra reading: the rice genome project

After the HGP, the genomes of bacteria, yeast, the worm Caenorhabditis elegans, the fruit fly Drosophila and plants such as rice and Arabidopsis were also sequenced. Your textbook stops there; the rice details below are extra reading. Rice (Oryza sativa) feeds a large part of the world, including much of India. Its genome is small for a cereal, so it is a model for wheat, maize and other grasses. The International Rice Genome Sequencing Project, led by Japan, brought ten countries together, and India sequenced part of chromosome 11. The high-quality sequence was finished in 2005: about 389 million base pairs on 12 chromosomes, with roughly 37,500 predicted protein-coding genes, more than in humans. Breeders use it to find genes for yield, disease resistance and tolerance to flood and drought.

Comparing genome sizes (the rice figure is extra reading)

Problem

The human genome has about 3164.7 million bp and the rice genome about 389 million bp. (a) About how many times larger is the human genome? (b) If 99.9% of bases are the same in all people, about how many bases differ between two people?

Working

(a) 3164.7 ÷ 389 ≈ 8.1.
So the human genome is about 8 times the size of the rice genome.
(b) 0.1% of 3164.7 million = 3164.7 × 10⁶ × 0.001.
= 3.16 × 10⁶, about 3 million bases.

Answer

(a) About 8 times. (b) About 3.2 × 10⁶ (roughly 3 million) bases differ, which is what makes each person unique.

In real life

Rice genome data helped breeders move a flood-tolerance gene (Sub1) into popular Indian rice varieties, so the crop can survive up to about two weeks under water. Human SNP data is helping doctors predict how a person will respond to some medicines.

Exam angle

2 marks: “Differentiate between Expressed Sequence Tags and sequence annotation.” ESTs: identifying all the genes that are expressed as RNA. Sequence annotation: sequencing the whole genome, coding and non-coding, and later assigning functions to its regions.

3 marks: “List any six salient features of the human genome revealed by the HGP.” 3164.7 million bases; average gene 3000 bases, dystrophin 2.4 million; about 30,000 genes; 99.9% bases same in all people; under 2% codes for proteins; over 50% gene functions unknown; repeats form a large part; chromosome 1 most genes, Y fewest; about 1.4 million SNPs.

2 marks: “Name the vectors used in the HGP and the hosts in which DNA fragments were cloned.” Vectors: BAC (bacterial artificial chromosomes) and YAC (yeast artificial chromosomes). Hosts: bacteria and yeast.

Remember it

HGP numbers: 3164.7 million bases; 2.4 million dystrophin; 99.9% same; under 2% codes protein; chromosome 1 most, Y least.