Human Gene Evolution: Introduction and Hypothesis | Genetics

In this article we will discuss about the Introduction and hypothesis of human gene evolution.

Introduction to the Evolution of Human Gene:

Some chromosomes appear to have been relatively protected from change during pri­mate evolution, for example human chromo­some 19 and X. By contrast other chromo­somes have been prone to significant reorgani­zation for example human chromosomes 1, 2, 3 and 7.

The most frequent type of chromoso­mal change detected in primate evolution are inversions (especially pericentric), changes in the amount and localization of heterochromatin, fusions and fissions, and changes in the location of centromeres due to activation/ inactivation. Reciprocal translocations, dele­tions and insertions are much less frequent (Figure 24.1).

Studies of chromosome banding patterns and hybridization homologies between ape and human chromosomes have provided evidences for human chromosome-2 having arisen from the fusion of two acrocentric ancestral semen chromosomes.

This fusion probably occurred by telomere-telomere fusion at 2ql3 rather than by translocation after chro­mosome breakage. Probably the best under­stood human chromosome in terms of its evo­lution is the chromosome-21.

The equivalent of human chromosome-21 formed a large and unique chromosome together with chromo- some-3 in the eutherian ancestor. This chro­mosome was conserved without significant alterations only in Lemurs, Civets, and in the Pigs.

It underwent inversions in the tree shrew and in the cow. Various translocations involv­ing the portions corresponding to chromo- some-3 occurred in brown Lemur, cat, rabbit and mouse. In the primates, two independent fissions occurred.

In New-world monkeys, a small segment of chromosome-3 remained attached to chromosome-21 and this chromo­some then underwent further rearrangements like: an inversion in the marmoset the addition of heterochromatin in the Capuchin monkey and a translocation in the Saki monkey. Chromosome-21 was formed in the common ancestor of old world monkeys and underwent translocations with various equivalents of human chromosomes, in all the cercopithecidae.

Chromosome-21 was conserved without visible alterations in the black gibbon and the great apes. Although all human chromosomes are not always identical, because many chro­mosomes exhibit heteromorphism especially in the centromeric and satellite regions of the acrocentric chromosomes. Chromosomes 1, 9, 13, 14, 15, 16, 19, 21, 22 and Y are the most heteromorphic whilst chromosomes 2-8 and X are the least heteromorphic.

Of the two types of sex chromosomes, the Y-chromosomes have undergone significant changes, by contrast X-chromosome exhibits conservation. Now it is considered that mam­malian sex chromosomes are thought to be descended from a homologous pair of autosomes.

Hypothesis of Human Gene Evolution:

There are two hypothesis in this regard:

(1) X-driven hypothesis of Graves (1998) which proposes that the rapid evolu­tionary spreading of X-inactivation preceded the decay of Y-chromosomal genes and even drove its initial steps.

(2) Y-driven pathway of Jegalian and Page (1998) which suggested that many extant genes represent intermediates on a general pathway by which X-Y gene or genes clusters evolved from autosomal genes. Autosomal genes would have entered the pathway either by virtue of their presence on the emergent sex chromosomes or via translo­cation of an autosomal gene.

This would have been followed by suppression of X-Y recombination’s. These steps occurred either at the chromosomal or sub-chromosomal level and gave rise to functionally equivalent X- linked genes and Y-linked genes. Subsequently Y- gene decay, up-regulation of X-linked gene expression and X-inactivation interacted together resulting in an inactivated X-linked gene accompanied by the loss of the Y gene as described below:

Most of the human genes appear to have homologous in simple organisms implying a very ancient origin. There are relatively few examples of human genes which originated after the divergence of the human and chimpanzee lineages. One such example is the functional immunoglobulin gene ( V_k) which is very much human specific.

Another example is the Salivary amylase gene (AMY 1) located on chromosome 1p21. Apart from these human specific genes all other human genes can be classified according to their time of ori­gin, which are as follows:

1. Human genes originated after the diver­gence of old world and new world mon­key e.g., Haptoglobin gene, Rh blood group gene, etc.

2. Human genes originated during primate evolution—e.g.. Alcohol dehydrogenase gene, interferon-a gene, growth hormone gene clusters, etc.

3. Human genes originated during the diver­gence of mammals—e.g., blood coagula­tion gene clusters, transthyretin gene, ABO blood group genes, olfactory recep­tor genes, etc.

4. Human genes originated during the diver­gence of the vertebrates—e.g., c-myc protooncogene. Insulin like growth factor genes, etc.

5. Human genes originated during the diver­gence of the metazoan e.g., retina expressed genes, lipase gene family, tumor suppressor genes, etc.

6. Human genes originated during the diver­gence of animals and fungi—e.g., at least 5885 genes of Saccharomyces cerevisiae are significantly related to the sequence of human genome.

7. Human genes originated during the diver­gence of plants and animals—Some human genes have their counterpart in both plants and fungi implying that they originated before the divergence of the three kingdoms.

8. Human genes originated during the diver­gence of prokaryotes and eukaryotes— e.g., heoxokinase gene, prokaryotic σ fac­tors genes and eukaryotic transcription factors TBP genes,, etc.

Actually the human genomes have been largely constructed by a continual process of gene duplication and divergence utilizing a set of basic gene types many of which possess counterparts in the genomes of primitive organisms. Much of this gene diversification may have taken place in the “Cambrian explo­sion”.

Genes which have emerged during pri­mate evolution are relatively few in number and tend to involve the addition of new mem­bers to pre-existing multi gene families. A gene family is a group of related genes encoding proteins differing at fewer than half their amino acid positions. Now the question may arise that how the multi gene family arises? The members of multi gene families can evolve in three different ways which are:

(a) By concerted evolution which may operate through either unequal crossing over or gene conversion, e.g., rRNA and histone genes.

(b) By divergent evolution—which may operate through diversification which may have conferred a selective advantage; e.g.. Immunoglobulin V_H genes.

(c) By a birth and death process—which may operate by unequal crossing over and gene duplication. Gene duplication serves to create new genes whilst other genes are inac­tivated by deleterious mutations or eliminated by unequal crossing over, e.g.. Immunoglobu­lin V_H genes.