Fundamentals of Molecular Biology - V.I. Rezyapkin 2009

Genome Organization
The Human Genome

The Human Genome is diploid and represented by 23 pairs of Chromosomes, 22 of which are autosomes, with the remaining pair being sex chromosomes (X and Y chromosomes). Accordingly, it consists of 23 pairs of DNA molecules, ranging in length from 60 to 250 million bp. The Introduction/19.html">Primary Structure of the human genome was deciphered in 2001.

The total size of the haploid human genome is approximately 3,3*10⁹ bp, and the total length of its DNA (haploid genome) is about 1.8 m. Polypeptide-coding nucleotide sequences account for roughly 1.5% of The Genome. The human genome is estimated to contain between 20,000 and 26,000 protein-coding genes. Despite this, Gene Expression yields a significantly larger number of Proteins. This is because Alternative Splicing is widespread in humans, allowing a single gene to produce multiple distinct mRNAs during expression. As a result, the number of Polypeptides produced in human Cells exceeds the number of genes. A large number of pseudogenes have also been discovered in the human genome, the functional roles of which are yet to be elucidated.

In addition to polypeptide-encoding genes, the human genome contains genes for tRNA, rRNA, and snRNA. Specifically, the haploid genome harbors about 1,300 tRNA genes and approximately 200 rRNA genes.

The human genome contains numerous regulatory sequences responsible for gene expression. These are typically small in size and are located either adjacent to or within genes, though they can occasionally be found at considerable distances from them.

Genes are distributed unevenly across chromosomes within the human genome. Each chromosome contains both gene-rich and gene-poor regions. Table 11.5 presents average characteristics for various gene elements; however, actual human genes may deviate significantly from these average metrics. Genes with two exons are the most common in the human genome, but the number of exons can be much higher—for instance, 234 exons have been identified in the gene for the Muscle protein titin. The actual sizes of genes can also vary by orders of magnitude compared to the "average" gene. For example, the dystrophin gene is 2.4*10⁶ bp long, with exons accounting for 0.6% of its length and non-coding sequences making up 99.6%.

Table 11.5

Class="center">Average characteristics of various elements of human genes

Proteins encoded by human genes show the highest similarity to those encoded by animal genes. About 32% of human genes belong to the group of genes shared among eukaryotes, and approximately 21% are common to both eukaryotes and prokaryotes. Interestingly, human exons are somewhat shorter than those in other organisms, whereas introns are correspondingly longer.

As noted above, exons account for about 1.5% of the human genome, while introns make up roughly 25%. The remaining portion, which is approximately 2/3 of the genome, consists of intergenic DNA sequences, primarily represented by repetitive sequences such as transposable elements (TEs), satellite DNA, and others.

The Neanderthal genome has now been sequenced. It turned out that its DNA shares over 99% identity with that of modern humans. Differences in protein Amino acid sequences have been found to be minor, with roughly one amino acid substitution per 10 to 20 proteins. The FOXP2 gene, which is associated with speech, is identical in modern humans and Neanderthals, suggesting that Neanderthals may have had the capacity for speech.

The chimpanzee genome was sequenced in 2005. It consists of 2.8 billion bp and differs from the human genome by only 4%, with protein-coding genes differing by 1.2%. About 29% of human and chimpanzee genes are identical. Remarkably, such minor differences in genomic Organization result in profound phenotypic differences between these species.