ABSTRACT
Double muscling is a heritable
trait. It has been revealed that myostatin (MSTN) or growth differentiation
factor 8(GDF8) is the genetic agent of this trait. The gene is a myokine, a
protein that inhibits myogenesis (muscle cell growth and differentiation).
In-Silico genetic analysis was done to analyze the sequences of Myostatin gene
in cattle, sheep and goat. A total of thirty seven (37) nucleotides with their corresponding amino acid sequences comprising of
(26 for goat, 9 for cattle and 2 for sheep) were retrieved from the Genebank.
The genetic polymorphism with three variants (M180L, S276N, S279K), five
(K178N, V151L, E247D, Q329L, G355I) and six (R98H, I119T, S125M, G133S, T165N,
H328T) for goat, sheep and cattle respectively, appeared not to impair the gene
function while three variants (K153F, T240K, L270Q), six (S191P, W203L, S205C,
N222Q, D231C, R303G), seven (D110L, I158A, R175V, K193V, S205G, P301L, F353N)
were deleterious. The results revealed beneficial amino acid variants which can
be used as possible markers for growth and development in goats, sheep and
cattle. Although Capra and Ovis family had more propinquity and organized
branch in the phylogenetic tree, the Neigbour-joining showed that sequences of
the three species are similar. Also, goats and sheep appeared more similar in
their amino acid contents compared to cattle. However, the distribution pattern
was the same for the three species in respect of (aspartate 6.1, cysteine 3.5,
glutamate 6.7, methionine 2.1, phenylalanine 3.7, proline 6.4 and tyrosine 3.2
with leucine 9.9, as the highest). The results also showed that this gene has a
high degree of conservation during evolution of various species, which implies
that MSTN, is an essential factor in biological muscle control. Physicochemical
properties also showed extinction coefficient =51630 for sheep and cattle, half
life=30hours for goats, sheep and cattle and aliphatic index =84.45 for goats
and sheep, other parameters varied from one species to another. The secondary
protein structure prediction in the bovine myostatin protein showed highest
alpha helix (23.20%) and random coil (44.00%) with caprine and ovine at 22.67%
and 43.20%. However, the extended strand (25.87%) and beta turn (8.27%)
predictions were higher in both caprine and ovine species with bovine at 25.33%
and 7.47%. Tertiary protein structure prediction of goat and sheep are the same
while that of cattle differed. Furthermore, the results showed that capra and
ovis family are much similar in function compared to cattle. Finally, the
comparative inferences of myostatin gene sequences of the species studied conferred
similarity in goat and sheep than cattle.
1.0 CHAPTER ONE: GENERAL INTRODUCTION
1.1 INTRODUCTION
Improving agricultural production
and human food supply are the major human concern all over the world especially
in developing countries. Meat is a very important source of food to human as it
supplies protein and energy (Aleriza et al., 2014). The first step in
animal breeding was selection of the best animals by ranchers, but today
scientists consider recognizing genetic aspects of major genes affecting meat
production. In recent years, the tools of new molecular techniques developed
and caused the discovery of new growth factors that are involved in the
regulation of muscle mass (Diel et al., 2010). It has already been
pointed out that one of the interesting aspects of hypertrophy or double muscle
is the dramatically increased muscle as a result of a combination of muscle
fibre hyperplasia and hypertrophy (Mcpheron and Lee, 1997). The gene encoding
myostatin was discovered by geneticists Se-Jin Lee and Mcpherron Alexander who
also produced a strain of mutant mice that lack the gene. These Myostatin “Knockout”
mice have approximately twice as much as normal mice (Mc Pherron et al.,
1997) which were subsequently named “mighty mice”. The term myostatin also
known as (growth differentiation factor (GDF8) or MSTN gene is a myokine, a
protein produced by muscle cells that acts on muscle cells (autocrine function)
to inhibit myogenesis; muscle cell growth and differentiation. Myostatin is a
secreted growth differentiation factor (GDF8) that is a member of the
Transforming growth factor (TGF) beta protein family (Joulia-Ekaza and Cabello,
2007). Animal with mutant genotypes in GDF8 gene not only produce more meat,
the quality of the meat in their products is also different.
In these animals, the posterior
limbs are round and prominent, the muscle are in protrusion mood and clear
lines under the skin are visible. Prominent examples of mammals are Belgium
blue and pre-montese, which show significant characteristics of double-muscle
(Kambadur et al., 1997).
Myostatin referred to as growth
differentiation factor-8 (GDF8) is a member of the mammalian growth
transforming family (TGF-B Super family), which is expressed specifically in
developing an adult skeletal muscle (Gonzalez-Cadavid and Bhasin, 2004). Mice that
lack myostatin indicated a widespread increase in skeletal muscle mass due to
an increase in both myofiber size (hypertrophy) and myofiber number
(hyperplasia): (Mcpherron et al., 1997). Muscular
MSTN is synthesized as a
biologically inactive precursor molecule (Full length MSTN protein) comprising
3 domains, the signal peptide, the propeptide (N-Terminus), and the C- Terminal
domain. MSTN is composed of 375 amino acid precursors, and has same C-terminal
fragments of about 109 amino acid residue in mice, rats, human, swine, fowl and
turkey and only 3 amino acid residue in C- terminal region thereof are not the
same in monkeys, cows, and sheep, The C-terminal regions are expected to
include physiologically active portions of MSTN (Thomas et al.,
2000). Major effect of a single gene on processing yields opened a potential
channel for improving processing yields of animals using knockout
technology (Arif et al., 2002). Therefore, in present study, in-silicon
genetic analysis of sequence of myostatin gene in mammalian species is
important in understanding the evolution, differentiation and the effects of
polymorphism on the myostatin gene (MSTN ) and how they are related within and
among the mammalian species under study.
1.2 Objectives of the Study
The general objective of the study
was to analyze the myostatin gene in selected bovids (cattle, sheep and goat)
with a view to providing relevant genetic information for breeding and
selection programmes in the studied species in Nigeria.
The Specific objectives were to;
1.
Examine
the attendant effects of various amino acids substitutions of the myostatin
gene in the selected species.
2.
Examine
the genetic diversity of myostatin in silico on their evolution and
differentiation within and among species.
3.
Study the
various physicochemical properties of myostatin gene and;
4.
Predict
the secondary and tertiary structures of the myostatin gene in the selected
species.
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Item Type: Postgraduate Material | Attribute: 62 pages | Chapters: 1-5
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